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ANALGESICS AND
ANTIBIOTICS IN PEDIATRIC DENTISTRY
By DrAminahMPost graduate
Department of Pedodontics and Preventive Dentistry
ANTIBIOTICS
Contents REVIEW OF PEDIATRIC PHYSIOLOGY
PEDIATRIC DOSAGE FORMULA
INTRODUCTION
DEFINITION
HISTORY
SELECTION OF ANTIMICROBIALS
PRINCIPLES OF ANTIBIOTIC ADMINISTRATION
GOLDEN RULES FOR ANTIBIOTIC USAGE
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
CLASSIFICATION
MECHANISM OF ACTION
DRUGS
(INTRODUCTION CLASSIFICATION MECHANISM PHARMACOKINECTICS
ADVERSE REACTIONS RESISTANCE CONTRAINDICATIONS USES IN
DENTISTRY)
szlig-LACTAM ANTIBIOTICS MACROLIDES METRONIDAZOLE SULFONAMIDES COTRIMAZOLE TETRACYCLINE AMINOGLYCOSIDES CHLORAMPHENICOL
PROBLEMS THAT ARISE WITH THE USE OF ANTIBIOTICS ANTIBIOTIC RESISTANCE NEWER ANTIMICROBIALS USE OF ANTIBIOTICS
ENDODONTIC MANAGEMENTLEDERMIXTRIPLE ANTIBIOTIC PASTE
PERIODONTAL MANAGEMENT ORAL AND MAXILLOFACIAL MANAGEMENT PREGNANT PATIENTS
ANTIBIOTIC PROPHYLAXIS RISK GROUPS DENTAL PROCEDURES CHILDREN REGIMEN SURGICAL PROPHYLAXIS
MISUSE OF ANTIBIOTICS DRUG ALLERGY
DEVELOPMENT OF ALLERGY OVERDOSE GEL AND COOMBS REACTONS PENICILLIN ALLERGY AMPICILLIN RASH
ANTIBIOTIC SENSITIVITY TESTING ALLERGY TESTS CROSS REACTIVITY MANAGEMENT
TOXIC EFFECTS OF ANTIBIOTICS
REASONS FOR ANTIBIOTIC FAILURE
CONCLUSION
REFERENCES
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANTIBIOTICS
Contents REVIEW OF PEDIATRIC PHYSIOLOGY
PEDIATRIC DOSAGE FORMULA
INTRODUCTION
DEFINITION
HISTORY
SELECTION OF ANTIMICROBIALS
PRINCIPLES OF ANTIBIOTIC ADMINISTRATION
GOLDEN RULES FOR ANTIBIOTIC USAGE
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
CLASSIFICATION
MECHANISM OF ACTION
DRUGS
(INTRODUCTION CLASSIFICATION MECHANISM PHARMACOKINECTICS
ADVERSE REACTIONS RESISTANCE CONTRAINDICATIONS USES IN
DENTISTRY)
szlig-LACTAM ANTIBIOTICS MACROLIDES METRONIDAZOLE SULFONAMIDES COTRIMAZOLE TETRACYCLINE AMINOGLYCOSIDES CHLORAMPHENICOL
PROBLEMS THAT ARISE WITH THE USE OF ANTIBIOTICS ANTIBIOTIC RESISTANCE NEWER ANTIMICROBIALS USE OF ANTIBIOTICS
ENDODONTIC MANAGEMENTLEDERMIXTRIPLE ANTIBIOTIC PASTE
PERIODONTAL MANAGEMENT ORAL AND MAXILLOFACIAL MANAGEMENT PREGNANT PATIENTS
ANTIBIOTIC PROPHYLAXIS RISK GROUPS DENTAL PROCEDURES CHILDREN REGIMEN SURGICAL PROPHYLAXIS
MISUSE OF ANTIBIOTICS DRUG ALLERGY
DEVELOPMENT OF ALLERGY OVERDOSE GEL AND COOMBS REACTONS PENICILLIN ALLERGY AMPICILLIN RASH
ANTIBIOTIC SENSITIVITY TESTING ALLERGY TESTS CROSS REACTIVITY MANAGEMENT
TOXIC EFFECTS OF ANTIBIOTICS
REASONS FOR ANTIBIOTIC FAILURE
CONCLUSION
REFERENCES
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Contents REVIEW OF PEDIATRIC PHYSIOLOGY
PEDIATRIC DOSAGE FORMULA
INTRODUCTION
DEFINITION
HISTORY
SELECTION OF ANTIMICROBIALS
PRINCIPLES OF ANTIBIOTIC ADMINISTRATION
GOLDEN RULES FOR ANTIBIOTIC USAGE
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
CLASSIFICATION
MECHANISM OF ACTION
DRUGS
(INTRODUCTION CLASSIFICATION MECHANISM PHARMACOKINECTICS
ADVERSE REACTIONS RESISTANCE CONTRAINDICATIONS USES IN
DENTISTRY)
szlig-LACTAM ANTIBIOTICS MACROLIDES METRONIDAZOLE SULFONAMIDES COTRIMAZOLE TETRACYCLINE AMINOGLYCOSIDES CHLORAMPHENICOL
PROBLEMS THAT ARISE WITH THE USE OF ANTIBIOTICS ANTIBIOTIC RESISTANCE NEWER ANTIMICROBIALS USE OF ANTIBIOTICS
ENDODONTIC MANAGEMENTLEDERMIXTRIPLE ANTIBIOTIC PASTE
PERIODONTAL MANAGEMENT ORAL AND MAXILLOFACIAL MANAGEMENT PREGNANT PATIENTS
ANTIBIOTIC PROPHYLAXIS RISK GROUPS DENTAL PROCEDURES CHILDREN REGIMEN SURGICAL PROPHYLAXIS
MISUSE OF ANTIBIOTICS DRUG ALLERGY
DEVELOPMENT OF ALLERGY OVERDOSE GEL AND COOMBS REACTONS PENICILLIN ALLERGY AMPICILLIN RASH
ANTIBIOTIC SENSITIVITY TESTING ALLERGY TESTS CROSS REACTIVITY MANAGEMENT
TOXIC EFFECTS OF ANTIBIOTICS
REASONS FOR ANTIBIOTIC FAILURE
CONCLUSION
REFERENCES
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
DRUGS
(INTRODUCTION CLASSIFICATION MECHANISM PHARMACOKINECTICS
ADVERSE REACTIONS RESISTANCE CONTRAINDICATIONS USES IN
DENTISTRY)
szlig-LACTAM ANTIBIOTICS MACROLIDES METRONIDAZOLE SULFONAMIDES COTRIMAZOLE TETRACYCLINE AMINOGLYCOSIDES CHLORAMPHENICOL
PROBLEMS THAT ARISE WITH THE USE OF ANTIBIOTICS ANTIBIOTIC RESISTANCE NEWER ANTIMICROBIALS USE OF ANTIBIOTICS
ENDODONTIC MANAGEMENTLEDERMIXTRIPLE ANTIBIOTIC PASTE
PERIODONTAL MANAGEMENT ORAL AND MAXILLOFACIAL MANAGEMENT PREGNANT PATIENTS
ANTIBIOTIC PROPHYLAXIS RISK GROUPS DENTAL PROCEDURES CHILDREN REGIMEN SURGICAL PROPHYLAXIS
MISUSE OF ANTIBIOTICS DRUG ALLERGY
DEVELOPMENT OF ALLERGY OVERDOSE GEL AND COOMBS REACTONS PENICILLIN ALLERGY AMPICILLIN RASH
ANTIBIOTIC SENSITIVITY TESTING ALLERGY TESTS CROSS REACTIVITY MANAGEMENT
TOXIC EFFECTS OF ANTIBIOTICS
REASONS FOR ANTIBIOTIC FAILURE
CONCLUSION
REFERENCES
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
PROBLEMS THAT ARISE WITH THE USE OF ANTIBIOTICS ANTIBIOTIC RESISTANCE NEWER ANTIMICROBIALS USE OF ANTIBIOTICS
ENDODONTIC MANAGEMENTLEDERMIXTRIPLE ANTIBIOTIC PASTE
PERIODONTAL MANAGEMENT ORAL AND MAXILLOFACIAL MANAGEMENT PREGNANT PATIENTS
ANTIBIOTIC PROPHYLAXIS RISK GROUPS DENTAL PROCEDURES CHILDREN REGIMEN SURGICAL PROPHYLAXIS
MISUSE OF ANTIBIOTICS DRUG ALLERGY
DEVELOPMENT OF ALLERGY OVERDOSE GEL AND COOMBS REACTONS PENICILLIN ALLERGY AMPICILLIN RASH
ANTIBIOTIC SENSITIVITY TESTING ALLERGY TESTS CROSS REACTIVITY MANAGEMENT
TOXIC EFFECTS OF ANTIBIOTICS
REASONS FOR ANTIBIOTIC FAILURE
CONCLUSION
REFERENCES
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
MISUSE OF ANTIBIOTICS DRUG ALLERGY
DEVELOPMENT OF ALLERGY OVERDOSE GEL AND COOMBS REACTONS PENICILLIN ALLERGY AMPICILLIN RASH
ANTIBIOTIC SENSITIVITY TESTING ALLERGY TESTS CROSS REACTIVITY MANAGEMENT
TOXIC EFFECTS OF ANTIBIOTICS
REASONS FOR ANTIBIOTIC FAILURE
CONCLUSION
REFERENCES
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
QUICK REVIEW OF PEDIATRIC PHYSIOLOGY
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
DRUG CONSIDERATIONS
Child has high AV and low FRC the pediatric AVFRC ratio is almost five times that of an adult
(LERMAN 1933)
This ratio difference means that children react more rapidly to inhaled gases such as NO and halothane and can be adequately anesthetized with lowest gas concentrations than those required for adult patients
RESPIRATORY SYSTEM
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CARDIOVASCULAR SYSTEM
DRUG CONSIDERATIONS
Changes in cardiac output can drastically affect the uptake of inhaled anesthetic agent
It can even significantly depress the central nervous system and hence lower gas concentrations are recommended for pediatric patient than adults
Endodontic consideration for pediatric patients with cardiac ailments obturation to be done 1mm lesser to apex along with antibiotic prophylaxis
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
GASTRO INTESTINAL SYSTEM
PHYSIOLOGY and DRUG CONSIDERATIONS
bull Decreased acidity bull Altered motility bull Altered hepatic metabolismbull Infant liver is deficient of pseudocholinesterase and hence
succinylcholine is therefore administered with caution to infant patients
bull Why is the half-life more in pediatric patients
Acid labile drugs Ampicillin Erythromycin Amoxycillin
are more efficiently absorbed in neonatesinfants
Basic drugs Diazepem are more rapidly absorbed than adults
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
RENAL SYSTEM bull The young kidney is less competent to excrete drugbull The GF participates in the excretion of commonly used pediatric drugs such
as the penicillins short-acting barbiturates and phenobarbital
Alterations in Body fluidbull Water equals 80 of infants weight( water soluble drugs have to be dosed at higher levels per unit of body weight )
ANDERSON 1991
Plasma protein differencesbull Serum albumin and plasma globulin are deficient in the newborn and
young infancy(warfarin and digoxin must be dosed at low levels per unit of body weight in these patients)
RADDE 1993a
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Pediatric dose = Childs BSA in m2
173m2x Adult Dosage
Pediatric = Dose
childs age in months 150 x Adult DoseFrieds Rule
Pediatric =dose
childs age in yearschilds age in years +
12 yearsx Adult DoseYoungs Rule
Clarks RulePediatric
Dose =childs weight lb(kg)
150lb(70kg) x Adult Dose
Nomogram Method
Pediatric Dosage formulas
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Several rules exist to compute the dosage of a drug for a child the most common Clarkrsquos rule Clarkrsquos rule determines the dose suitable for a child based on the typical adult weight of 150 lb (or 70 kg)
Clarks rule
Pediatric = dose
childs weight lb(kg) 150lb(70kg) x Adult Dose
For example if the adult dose of Penicillin V is 500mg every 6 hours the dose for a 40 lb (18 kg) paediatric patient would be calculated as
133 mg every 6 hrs = 40 lb(18 kg)
150lb(70kg) x 500mg
Clarkrsquos rule may also be used to calculate dosages for underweight ill or elderly patients
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Introduction
Antibiotics are one of the most frequently used as well as misused drugs
Their importance is magnified in the developing countries where infective diseases predominate
Selman A Waksman introduced the term ldquoantibioticrdquo in 1942
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
In dentistry antibiotics are used mainly in the following purposes 1) as adjuncts to therapy for oro-facial infection 2) to prevent local infection associated with dental
procedures 3) to prevent the spread of oral micro-organisms to
susceptible sites elsewhere in the body
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotics are the substances produced by microorganisms which suppress the growth or kill other microorganism at very low concentration without causing any harm to host
The term antibiotic means against liferdquo
(Tripathi Essentials of medical pharmacology)
DEFINITION
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Brief history of Antibiotics
1928 1956
1932 1962
1948 1970
1952 2000
Fluoroquinolones
Sulphonamides -Erlich
Cephalosporins-GBrotzu
Erythromycin - Mc Guire
Vancomycin-MHCormick
Quinolone
Linezolide
Penicillin-Fleming
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
FUNDAMENTAL CONCEPTS OF ANTIBIOTIC THERAPY
Identify causative organism
Most effective narrow spectrum antibiotics should be used
A bacteriostatic drug should not be used with a bactericidal antibioticProper route dose and duration of antibiotic should be managed Combination therapy
19
Principles of antibiotic administrati
on
Proper Time
Interval
Proper Route Of Administ
ration
Consistency in
route of administr
ation
Proper Dose
Combination
antibiotic therapy
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Dont use antibiotics unnecessarily
Avoid broad spectrum Antibiotics as far as possible
Donrsquot prolong the antibiotic therapy unnecessarily
In cases of chronic infections like Tuberculosis Leprosy etc employ multiple drug regime
GOLDEN RULES FOR ANTIBIOTIC USAGE
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotics with specification
Effective against odontogenic infections -------- Penicillin
Clindamycin
Erythromycin
Cefadroxil
Metronidazole
Tetracyclines
Amoxicillin ------ first choice antibiotic against endocarditis prophylaxis
Child is allergic to penicillin ------ Macrolides Clarithromycin and Azithromycin
Metronidazole ------ Against anaerobic bacteria
Cefadroxil ------- Commonly used under cephalosporin
Tetracyclines ------- Limited use in dentistry
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Classification
Sulfonamides
Sulfadiazine Dapsone
Quinolones Norfloxacin Ciprofloxacin
Tetracyclines Tetracycline Doxycycline
β-lactam antibiotics Penicillins
Cephalosporins
Aminoglycosides
Streptomyci
n Gentamicin
Nitrobenzene
derivatives
Chloramphenicol
Macrolides Erythromyci
n Azithromycin
Nitroimidazoles
Metronidazole Tinidazole
Lincosamide Clindamycin
Lincomycin
Glycopeptides
Vancomycin
Based on chemical structure
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Based on type of ActionBacteriostatic Sulfonamides Tetracyclines
Chloramphenicol Erythromycin Ethambutol Clindamycin
Bactericidal Penicillins
Cephalosporins Aminoglycosides Metronidazole Ciprofloxacin
Based on spectrum of ActivityNarrow Spectrum
Penicillin GStreptomycin Erythromycin
Broad SpectrumTetracycline
Chloramphenicol
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Based on their sites of action and its mechanism
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
The antibiotics administered for 5 days following resolution of major clinical signs and symptoms of infection
Following treatment of the source of infection and adjunctive antibiotic therapy significant improvement in patients status should be seen in 24 to 48 hours
If improvement is not seen within 48 hrs a combined use of antibiotics may be recommended
26
DURATION OF ANTIBIOTIC THERAPY
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Beta-Lactam Antibiotics
bull These have a β-lactam ringbull Two major groups
Penicillins Cephalosporinsbull Also Carbapenem and Monobactamsbull They act by inhibiting the cell wall synthesis
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Penicillins
Introductionbull First antibiotic to be used in 1941bull Obtained originally from the fungus Penicillium notatumbull Presently obtained from Pchrysogenumbull Has wide therapeutic range and is a safest drugbull Most commonly used penicillin is Penicillin G or Benzyl Penicillin
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Mechanism of Action
Bactericidal drugs
Penicillins interfere with the last step of bacterial cell wall synthesis resulting in exposure of the osmotically less stable membrane leading to cell lysis
1 Penicillin binding proteins(PBPs)2 Inhibition of transpeptidase3 Production of autolysins
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Classification
Penicillin
Natural Penicillin Penicillin G (Benzyl Penicillin)
Semi synthetic Penicillin
Penicillinase resistant penicillinsMethicillin Cloxacillin
Extended spectrum penicillinAmpicillin Amoxicillin Carbenicillin
Piperacillin
Acid resistant alternative to Penicillin G Phenoxymethyl penicillin
(Penicillin V)
β-lactamase Inhibitors
Clavulanic acidSulbactam
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Penicillin G
bull Narrow spectrum antibioticbull Activity limited to gram positive
bacteriabull Susceptible to inactivation by β-
lactamases
Resistance1 β-lactamase activity
2 Decreased permeability to the drug
3 Altered PBPs
Pharmacokinetics
Penicillin G is destroyed by gastric acid
Should be given IVIM Insignificant metabolism as it is
rapidly excreted from the body Poor penetration into CSF
Adverse Drug Reactions1 Hypersensitivity 2 Angioedema3 Super infection4 Diarrhoea 5 Jarisch- Hexheimer reaction
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Amoxicillin
Better oral absorption Higher and sustained blood
levels are produced Diarrhoea is rare
Dose 025-1g TDSorallyim 125mg5ml syrup
Commonly used in dental practice
Acid stable better oral absorption
Uses Streptococcal pharyngitis Sinusitis trench mouthActinomycosis
Dose Infants 60mg Children 125-250mg given 6
hourly
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Uses in dentistry
Amoxicillin is the most
frequently prescribed drug for
infections of dental origin
In infections associated with both gram +ve
and ndashve aerobic and anaerobic organisms amoxicillin
combined with metronidazole is the agent of
choice
It is administered
orally which is the safest most convenient and least expensive mode of drug
administration
Many physicians now prefer it over ampicillin for Bronchitis Urinary infections SABE Gonorrhoea
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Cephalosporins
INTRODUCTION Semisynthetic antibiotics derived from Cephalosporin-C obtained from the
fungus Cephalosporium Chemically related to penicillins Effective against both gram +ve and gram ndashve organisms Bactericidal drugs Inhibit cell wall synthesis
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CLASSIFICATIONFirst generation-
Second generation-
Third generation-
Fourth generation-
Fifth generation-
bull More active against gram +ve organism
bull Against gram +ve and gram
-ve organism
bull Highly active against gram -ve organisms and pseudomonas
bull Similar to third generation but highly effective
bull Developed in the lab to specifically target resistant strains of bacteria
CephalothinCephalexinCefadroxil
CefuroximCefoxitinCefaclor
CefotaximeCeftizoximeCeftazidimeCefixime
CefepimeCefpirome
CeftobiproleCeftraroline
(both act against MRSA)
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Pharmacokinetics
IV IM administration Doesnrsquot undergo any
metabolism in the body Good distribution into body
fluids Good penetration into bones Eliminated through tubular
secretion and glomerular filtration
Adverse reaction
Allergic manifestations It should be avoided in those allergic to penicillin Disulfiram like effect Bleeding Cephalexincefaclor - oro-dental infections
Cefazolincefotaxime- surgical prophylaxis in dental surgeries
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Macrolides
Erythromycin bull Used as an alternative to
penicillin in individuals who are allergic to β-lactam antibiotics
Newer Macrolidesbull Roxithromycinbull Clarithromycin bull Azithromycin
Mechanism of Action
bull Bacteriostatic at low concentration and bactericidal at high concentration
bull Macrolides bind irreversibly to a site on the 50S subunit and interferes with translocation thus inhibiting protein synthesis
bull They have a large lactone ringbull They are alternative to penicillins in many conditions
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Pharmacokinetics
Acid labile given as enteric coated tablets
Food interferes with absorption Widely distributed in the body Crosses the placenta but not the
BBB Metabolized and excreted in bile Minor renal excretion (hence
can be given in pts with renal failure)
Adverse drug reactions
Epigastric distress Ototoxicity Cholestatic jaundice Occurs
with the estolate form Contraindicated in pregnant
patients
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Uses in dentistry
It has a long and successful history of
use against acute oro-facial infections
Used as a substitute for patients allergic
to penicillin
Azithromycin at 500mgday for 3 days
has demonstrated comparable efficacy to amoxicillin at 500mg three times daily for
5-10 days in the management of acute periapical abscesses
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Metronidazole
INTRODUCTION
Synthetic nitroimidazole Anti-protozoal drug Used extensively for the
treatment of anaerobic bacterial infections
Mechanism of action
Bactericidal drug Affects DNA synthesis It enters into the cell and
reduces into its nitro group to produce metabolites that damage DNA eventually inducing cell death
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Pharmacokinetics
Completely absorbed from the GIT
Widely distributed in the body
Excellent CNS penetration
Metabolised in liver
Adverse drug reactions
Nausea and vomiting Reversible neutropenia Metallic taste Dark or red brown
urine
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
USES
Bone and joint infections septicemia Endometritis or endocarditis Pseudomembranous colitis due to Clostridium difficile peptic ulcer disease Periapical abscess periodontal abscess acute
pericoronitis of impacted or partially erupted teeth
Often used in conjunction with Amoxicillin
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Sulfonamides
Introduction
Were the first antimicrobial agents effective against pyogenic bacterial infections
Limited use currently due to rapid development of bacterial resistance
Mechanism of action
PABA (p-aminobenzoic acid)
Folic acid
Sulfonamides
Inhibit the bacterial folate synthase
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Uses Topically used to prevent
infection on burn surfaces Combined with
trimethoprim for many bacterial infections
Not used to treat dental infections
Adverse reactions
Crystalluria nephrotoxicity may result
Hypersensitivity Hematopoietic
disturbances in patients with G6PD deficiency
Kernicterus may occur in newborn
Contraindications
Newborns and infants lt 2months
Pregnancy
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Cotrimoxazole
Introduction
bull Trimethoprim + Sulfamethaxazole = Cotrimoxazole
bull It has a synergistic bactericidal action
bull Greater antibacterial activity
Mechanism of action
PABA
Dihydrofolate (DHFA)
Tetrahydrofolate(THFA)
Sulfonamide - - -
Trimethoprim - - -
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibacterial spectrum
Broader spectrum of action
Effective in treating UTIs RTIs Gonorrhea Otitis media Pneumocystis
pneumonia (in AIDS)
Adverse reactions
Nausea vomitting stomatitis Megaloblastic anemia
leukopenia thrombocytopenia (can be reversed by administration of folic acid)
High incidence of fever rash bone marrow hypoplasia in AIDS patient
Renal toxicity
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Tetracycline
Introduction These are a class of antibiotics
having a nucleus of four cyclic rings Broad spectrum of action
Resistance Inability of the organism to
accumulate the drug Production of bacterial proteins that
prevent tetracyclines from binding to the ribosome
Mechanism of Action
Bacteriostatic agent Inhibit protein synthesis by
binding to 30S ribosomes thereby blocking access to the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Uses
bull Chronic periodontitis Doxycycline 20mg bid daily for 2-4 weeksbull Travellerrsquos diarrhoeabull Acne treatment Tetracycline 250mg bid for 4 weeks
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Pharmacokinetics
Adequately but incompletely absorbed after oral ingestion
High concentration in liver kidney spleen and skin
Enterohepatic circulation is a feature of tetracyclines
Binds to tissue undergoing calcification (teeth and bone)
Crosses the placental barrier and concentrates in fetal bones and dentition
Excreted by kidney
Adverse Drug Reactions
Gastric discomfort epigastric pain nausea vomitting diarrhoea
Effects on calcified tissue alcium Tetracycline chelate gets deposited
in developing teeth and bone (Midpregnancy to 5mths of extrauterine life deciduous teeth are affected)
Fetal hepatotoxicity Photosensitivity Vestibular toxicity Superinfections Nephrotoxicity
Not recommended for the treatment of infections
of dental origin upto the age of 12 years as it
causes permanent yellowing or graying of the
teeth and it can affect a childs growth
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Aminoglycosides Introduction
All are bactericidal and more active at alkaline pH
Do not penetrate brain or CSF Drug of choice for aerobic
gram ndashve infections Used as anti-tuberculous drug Includes
1 Streptomycin 2 Gentamycin3 Tobramycin4 Amikacin5 Kanamycin
Mechanism of Action
They act by blocking the mRNA thus inhibiting bacterial protein synthesis
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Resistance Decreased uptake of drug An altered 30S ribosomal subunit
aminoglycoside binding site that has a decreased affinity for the drug
Plasmid associated synthesis of enzymes that modify and inactivate aminoglycosides
Adverse drug reactions
Ototoxicy Nephrotoxicity Neuro muscular toxicity
Precautions amp Contraindications Avoid during pregnancy Cautious use in patients those with kidney damage Avoid concurrent use of other ototoxic and nephrotoxic
drugs
Not used to treat dental infections
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Chloramphenicol
Active against a wide range of gram +ve and ndashve organisms
Pharmacokinetics
Oral IV administration Widely distributed in the body Enters the CSF Metabolised in the liver to
glucoronic acid and then secreted by the renal tubule
Mechanism of Action
It binds to bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Resistance
Presence of an R factor that codes for an acetyl coenzyme acetyl-transferase which inactivates chloromphenical
Inability of the drug to
penetrate the organism
Adverse drug reactions Hypersensitivity Gray baby syndrome (due to
cardio vascular collapse and glucuronyl transferase in infants)
Bone marrow depression
Antimicrobial Spectrum
Broad spectrum antibiotic
Excellent activity against anaerobes
Maybe bacteriostatic or bactericidal depending upon the concentration
Drug of choice for typhoid
Contraindicated in infants
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Problems that arise with the use of antibiotics
1 Toxicity-Local
-Systemic
Hypersensitivity Reactions
Drug Resistance-Natural -Acquired
-Cross Resistance
Super infectionMasking of an
infection
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANTIBIOTIC RESISTANCE
55
The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bread out which can be passed to other individuals and from them to other until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save
Sir Alexander Flemming
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
COMMON MODES OF ANTIMICROBIAL RESISTANCE
egPenicillins
eg aminoglycosides chloramphenicol amp penicillins
egtetracyclines
eg aminoglycosides amp tetracyclines
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
MECHANISM OF MICROBIAL RESISTANCE TO ANTIBIOTICS
bull ENZYMATIC ANTIBIOTIC INACTIVATION β lactamases β lactams
(Penicillins Cephalosporins)
Acetyltransferases (Aminoglycosides
Chloramphenicol Streptomycins)
57Splits the amide bond hydrolyzing the β-lactam ring
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
WHO IS THE WINNER
bull The microbe always has the last world
-LOUIS PASTEUR (1822-1895)
58
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Need newer antimicrobials why
bull Bacterial resistance to antimicrobials develop
bull Health and economic problems
bull Chronic resistant infections contribute to increasing health care cost
bull Increase morbidity amp mortality with resistant microorganisms
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Newer Oxazolidinones
Linezolid- Approved for adults use in
2000 Recently approved for
pediatric use in 2005
MOA Bind to the 23S portion of
the 50S subunit preventing translation initiation
Newer Cephalosporins
Ceftaroline Approved in 2010
For the treatment of o community - acquired
pneumonia ampo complicated skin and
soft - tissue infectionsBind strongly to (MRSA)
DOSE 600 mg IV every 12 hours
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
NEWER Lipopeptides
Daptomycin-Only drug in this class
Approved in 2003 Rapidly bactericidal No cross resistance
Warning issued by FDA in July 2010------can cause life-threatening eosinophilic pneumonia
NEWER Glycylcyclines
Only one glycylcycline antibiotic for clinical use TIGECYCLINE Approved in 2005
MOA Bind to 30 S subunit of
bacterial ribosome 20-fold more efficient
than tetracycline Slow IV infusion of 100
mg Also active against MRSA
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
USE OF ANTIBIOTICS IN ENDODONTIC TREATMENT
Once the source of infection has been established dental procedures should be used immediately to disrupt the microorganisms involved
Antibiotics should be used as an adjunct
62
1 = apical foramen with delta 2 = lateral accessory canal 3 = furcation accessory canal 4 = dentinal tubules
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ROUTES OF ENDODONTIC INFECTION (MICROBIAL INGRESS)
ndash Through open cavityndash Through dentinal tubulesndash Through gingival sulcus or periodontal
ligamentndash Through the blood streamndash Through a broken occlusal seal or faulty
restorations of a tooth previously treated by endodontic therapy
ndash Through extension of a periapical infection from adjacent teeth
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Systemic involvement
Fevergt 100degF Malaise Lymphadenopathy Trismus
Progress ive infe ction (pre se ntsuspe cte d)
bull Increasing swelling bull Cellulitisbull Osteomyelitis
In treatment of endodontic infections antibiotics are indicated (as an adjunct) when certain signs and symptoms of involvement are evidentThese include
Cavernous sinus thrombosis Ludwigs angina Mediastinal space swelling Brain abscess
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
LEDERMIX
bull It is highly effective anti-inflammatory cortisone derivative combined with a broad range antibiotic (di-methyl chlor tetracycline)
bull Therapeutical results Rapid relief of pain associated with acute pulpal amp PDL inflammations
65
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Triple Antibiotic Paste
METRONIDAZOLE CIPROFLOXACIN AND MINOCYCLINE Combination would be needed ndashin case of diverse flora in root canal
TAP first tested by Sato et al
bull Metronidazole (nitroimidazole) -a broad spectrum against protozoa ampanaerobic bacteria
bull Minocycline (semisynthetic tetracycline) a similar spectrum of activity
bull Ciprofloxacin a synthetic fluoroquinolone a bactericidal mode of action
bull 30 reduction in bacteria -2 weeksbull Successful treatment
- sterilization of canals and healing of periapical pathology immature root development necrotic pulps and apical periodontitis
bull Drawbacks of this technique Development of resistant bacterial strains and tooth discoloration
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotics in periodontal management
Chronic inflammatory periodontal diseases-bullTOPICAL MEASURES ndash
Tetracyclins metronidazole 250mg tid Penicillins 500mg qid Cephalosporins
ANUG-Topical measures with systemic antibiotic penicillin metronidazole 400mg qid
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotics in oral and maxillofacial management
Initial stage - Aerobic bacteria
invade
Severe infection-
Aerobic and anaerobic
bacteria invade
Advanced stage-
Anaerobic infection
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Therapeutic uses of antibiotics in maxillofacial surgery
Pericoronitis Acute pericoronitis severe antibiotic therapy
Treatment - Debridement drainage of the site Penicillin 500 mg qid Amoxicillin 500mg qid Clindamycin 300mg qid
Dento-alveolar Abscess
Acute dento-alveolar abscess and cellulitis
Treatment Penicillin is the drug of choice
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Regimen for fracturebullTherapeutic doses - 10 to 14 daysbullShould begin as early as possible after diagnosisPre-operativelybull Penicillin 2 million units or bull Cefazolin 05 gm-15 gm 12 hr [25- 50 mgkg]Post-operativelybull Penicillin 500mg 6 hr [30-40 mg kg]bull Cephalexin 500mg 6 hr [25- 50 mgkg]
In suspected intra-cranial contaminationbull Pre-operatively- Naficillin 2-6 gmkg 6hr+ Gentamycin 3-5mgkg 8 hrbull Post-operatrively- Cephalexin 500mg 6 hr[25-50 mgkg]
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
PREGNANCY AND ANTIBIOTICS Safe antibiotics in pregnancyPenicillinsCephalosporinsAmoxicillin Clindamycin
Drugs contraindicated in children- Chloramphenicol Tetracycline
Unsafe antibiotics in pregnancyClarithromycin CiprofloxacinTetracycline
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Drugs contraindicated in lactating mother Metronidazole Tetracycline Sulfonamides Aminoglycosides Cotrimazole
Safe drug in lactating mother Cephalexin
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Triple Antibiotic Paste
3 Mix- pasteCiprofloxacin - 200mgMetronidazole - 500mgMinocycline - 100mg
The drugs are powdered and mixed Acc To Hoshino et al ratio = 111
carrier (MP) ratio = 11Macrogol ointment Propylene glycol
Acc To Takushige et al ratio = 133 and add either Macrogol propylene glycol or a canal sealer
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
COMBINATION THERAPY
AUGMENTIN Amoxicillin trihydrate + Potassium Clavulanate( 25mg + 625mg )Pharmacological form child lt6years - oral suspension(125mg3125mg 5ml powder ) - pediatric sachetschild gt6years - tabletschildren lt40kg - 20mg5mg kg day - 60mg15mgdaygiven in three divided dosesContra-indicated in case if there is history of jaundice severe immediate hypersensitivity rxns
No clinical data on doses of augmentin 41 formulations higher than 40mg10mgkg per day in children under 2 years have been reported
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANTIBIOTIC PROPHYLAXIS
77
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotic prophylaxis is recommended for the following
High-risk category
Prosthetic cardiac valves including bio-prosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease
Surgically constructed systemic pulmonary shunts
Moderate-risk category
Most other congenital cardiac malformations
Acquired valvular dysfunction (eg rheumatic heart disease)
Hypertrophic cardiomyopathy Mitral valve prolapse with
valvular regurgitation
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotic prophylaxis in dental procedures
RECOMMENDED - All dental procedures that involve gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
NOT RECOMMENDED ndash Restorative dentistry (operative and prosthodontic) with or without
retraction cord ndash Local anesthetic injections ndash Intracanal endodontic treatment post placement and buildup ndash Placement of rubber dams postoperative suture removal taking of
oral impressions and fluoride treatments ndash Placement of removable prosthodontic or orthodontic appliances ndash Taking of oral radiographs ndash Shedding of primary teeth
79
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
THE AMERICAN ACADEMY OF PEDIATRIC DENTISTRY (AAPD)
Antibiotic prophylactic regimen JULY 2015
Clindamycin 20mgkg (maximum 600mg) IV or IM within 30 min before dental procedure
Children allergic to penicillin and unable to take oral medications
Clindamycin 20mgkg (maximum 600mg) orally 1 h prior to dental procedure
Children allergic to penicillin
Ampicillin 50mg kg (maximum 2g)IV or IM within 30 min before dental procedure
Children not allergic to penicillin and unable to take oral medications
Amoxicillin 50mgkg (maximum 2g) orally 1 hr prior to dental procedure
Children not allergic to penicillin
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Under LAAmoxicillin 3 gmkg or clindamycin 600mg 1 hr pre- operatively and amoxicillin 1gm after 6 hr
Under GAAmoxicillin 05 gm IM after 6 hr or 3 gm 4 hr + 1 gm probencid post-operatively (OR)Clarithromycin 500mg or azithromycin 2 gm 6 hr post- operatively
Surgical prophylaxis
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
MISUSE OF ANTIBIOTICS
Treatment of Nonresponsive InfectionsTherapy of Fever of Unknown OriginImproper DosageInappropriate Reliability on Chemotherapy aloneLack of Adequate Bacteriological InformationAntibioma
82
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Drug Interactions in Clinical Dentistry
83
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Antibiotics Interacting drug Effect and Recommendation
Penicillin V ampicillin Cephalexin Vancomycin
Bacteriostatic antibiotics (erythromycin tetracyclines clindamycin)
Bacteriostatic antibiotic interferes with action of bactercidial antibiotic
Penicillin V ampicillin Tetracycline
Oral Contraceptives Decrease the activity of oral contraceptive drug
Ampicillin Allopurinol High incidence of skin rash substitute amoxicillin for ampicillin
Erythromycin Carbamazipine cyclosporine warfarin
Erythromycin interferes with metabolism of these drugs
Metronidazole Alcohol Disulfiram like effect
Erythromycin tetracyclines
Bactericidal antibiotics (penicillins Cephalosporins)
Action of bactericidal agent inhibited
Doxycycline Barbiturates alcohol phenytoin carbamazepine
Hepatic clearance of Doxy is increased Adjust dose upward or use alternative tetracycline
Clindamycin Erythromycin and Chloramphenicol are mutually
antagonistic because of similar binding sites on bacterial
ribosome
------so never be given concurrently
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Adverse drug reactions
1 to 15 of drug causesMajority iatrogenic illnesses
85
Non-immunologic (90-95) Side effects toxic reactions drug interactions secondary or indirect effects (eg opiate reactions NSAID reactions)
Immunologic (5-10)
DRUG ALLERY
Factors influencingRoute of administrationParenteral route more likely to cause sensitization and anaphylaxis than oral routeInhalational route respiratory or conjunctival manifestations onlyTopical high incidence of sensitization
Nature of the drug 80 of allergic drug reactions due to - penicillin - cephalosporins - sulphonamides - NSAIDs
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Overdose
Drug toxicity
ndash Hepatotoxicity ndash Nephrotoxicityndash Iatrogenic diseasesndash Skin reactionsndash Teratogenic effects
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Coombs and Gel reactions
Type 1 Immediate Hypersensitivity
IgE-mediated
occurs within minutes to 4-6 hours of drug exposure
Type 2 Cytotoxic reactions antibody-drug interaction on the cell
surface results in destruction of the cell
eg hemolytic anemia due to penicillin quinidine cephalosporins
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Type 3 Serum sickness
Fever rash (urticaria angioedema palpable purpura arthralgia lymphadenopathy splenomaly
onset 2 days up to 4 weeks penicillin commonest cause
Type 4 Delayed type hypersensitivity
sensitized to drug or preservative (eg PABA parabens )
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Penicillin Allergy 2 of penicillin causesbull Penicillin metabolites --95 benzylpenicilloyl moiety (ldquomajor determinantrdquo)--5 benzyl penicillin G penicilloates (ldquominor determinantrdquo)bull Resolution of penicillin allergy -- 50 resolution of allergy in 5 y --- 80-90 resolution of allergy in 10 yr
If treatment is definitely required administer an alternative non-penicillin antibiotic (eg cephalosporinvancomycin gentamycin or non beta-lactam antibiotic) If a penicillin is definitely indicated proceed with therapy treating mild reactions symptomatically
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Ampicillin rash
bull non-immunologic rashbull maculopapular non-pruritic
rashbull onsets 3 to 8 days during the
antibiotic coursebull incidence 5 to 9 of
ampicillin or amoxicillin courses 69 to 100 in those with infectious mononucleosis or acute lymphocytic leukemia
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANTIBIOTIC SENSITIVITY TESTING
bull This test determines the effectiveness of antibiotics against microorganisms (eg bacteria) that have been isolated from cultures
bull Sensitivity analysis may be performed along with1 Blood culture 2 Urine culture (clean catch) or urine culture (catheterized
specimen) 3 Sputum culture4 Throat culture5 Wound and other cultures
bull Why is the Test Performed The test shows which antibiotic drugs should be used to treat an
infection
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Broth dilution susceptability test
bull uses a micro dilution plate
bull quantitative results obtained
Disc diffusion method
bull qualitative susceptability result are obtained
Gradient diffusion test [ E- test]-
bull qualitative susceptability results
obtained
DETERMINATION OF ANTIBIOTIC SENSITIVITY
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANTIBIOTIC ALLERGY TESTSbullNO SINGLE TEST FOR ANTIBIOTIC ALLERGY bullExcept Penicillin immunoreactive drug metabolites rarely identified IgE-mediated hypersensitivity
SKIN TESTING -
bullIntradermal skin testing is difficult to do in children under 10 years of age
bullMost non-pruritic maculopapular rashes can not be predicted by skin testing
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Cross reactivity
1 Semi synthetic penicillins (ticarcillin and piperacillin) has same nucleus as penicillin G
2 Cephalosporins share a common beta-lactam ring with the penicillins hence cross-reactivity is quite low
3 3-7 of those with penicillin allergy show allergic reactions to cephalosporins as well
4 Monobactams (aztreonam) safely administered to penicillin allergic subjects
5 Carbapenems (imipenem) can be given to penicillin-allergic patients
ASCIA HPIP Antibiotic allergy 2014
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
TOXIC EFFECTS OF ANTIBIOTIC Some antibiotic kill injure human cells
Aminoglycosides
Renal urinary system
Erythromycin Pseudomembranous colitis Diarrhoea Clindamycin Hepatitis Tetracycline
Gastrointestinal system
Vertigo Vancomycin Myoclonic seizures Penicillin and cephalosporin VertigoGentamicin Deafness Tobramycin
Nervous system
Carbpenicillin (and ticarcillin) Grey baby syndrome Chloramphenicol
Hematologic PROBLEM ANTIBIOTIC
Renal tubular necrosis
Decreased platelet aggregation
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Common reasons for antibiotic failure
Failure to surgically eradicate the source of the infection Too low blood antibiotic concentration Inability of the antibiotic to penetrate to the site of infection Impairedinadequate host deafness Inappropriate choice of antibiotic Limited vascularity or blood flow Decreased tissue pH or oxygen tension Emergence of antibiotic resistance Delay in diagnosis Incorrect diagnosis Antibiotic antagonism
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CONCLUSION
ldquoMicrobes will leave us alone if we leave them alonerdquo
Use of antimicrobials have to be reduced to the level where they are necessary for our survival amp not merely for Dr amp patient comfort
97
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
98
ldquoWITH ANTIBIOTICS NO PERSON IS AN ISLANDrdquo
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
List of references
1NDTripathi Essentials of medical pharmacology7th edition 2001 123-342 RSSathoskar SDBhandarkar and SSAinipune Antibiotics Textbook of pharmacology and pharmacotheraphy 2nd edition 1999 123-363 lippincotts textbook of pharmacology4Chaudhuri Antimicrobial agents Textbook of Quintessae of medical pharmacology 1st edition 200167-895BowmagartenTorabimajed etal Journal of Endodontics vol 12004 page no 45-526In Search For Endodontic PathogensSuchitra U KUNDABALA M Shenoy MM- KUMJ 2006 Vol4No4Issue 16525-529 7 Antibiotic Prophylaxis in dentistryA Review amp Practice recommendations-JADA Vol 131 March 2000 366-374
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
8 Infective Endocarditis dentistry and antibiotic prophylaxis time for a
rethink (BDJ Dec 2000 Vol 189No 11 page 610-616)
9 Antibiotic resistance in general dental practicemdasha cause for concern
Journal of Antimicrobial Chemotherapy (2004) 53 567ndash576
10Text book of Pediatric Dentistry SG Damle 3rd Edition
11Textbook of pediatric dentistry Pinkham
12Textbook of pediatric dentistry Nelsonrsquos - Volume 1
13Textbook of Oral amp Maxillofacial Surgery Neelima Malik 1st Edition
14Pediatric Dental Medicine Donald J Forrester
100
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANALGESICS IN PEDIATRIC DENTISTRY
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Contents INTRODUCTION DEFINITION PAIN IN DENTISTRY ANALGESICS
INTRODUCTION CLASSIFICATION SELECTION OF ANALGESICS ASPIRIN IBUPROFEN PARACETAMOL COXIBS
COMBINATION ANALGESICS DRUG INTERACTION OF NSAIDS PG SYNTHESIS----BENEFICIARY ASPECTS INHIBITORY ASPECTS ANALGESIC USE IN PREGNANCY AND LACTATION LIMITATION OF NSAIDS
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
OPIODS HISTORY CLASSIFICATION MECHANISM OF ACTION MORPHINE CODIENE PROPOXYPHENE OPIOD USES IN PULPAL ORIGIN DRUG INTERACTIONS OF OPIODS OPIOD DOSAGE WITHDRAWAL SYMPTOMS SIDE EFFECTS COMBINATION ANALGESICS
OTHER DRUGS WITH ANALGESIC EFFECTSTERIODS
PAIN CONTROL STRATEGY CONCLUSION PRINCIPLES OF PRESCRIPTION WRITING REFERENCES
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
INTRODUCTION
Pain plays a major role specially in treating kids
Poorly controlled pain contributes to anxiety among the pediatric patient about future treatment
Hence effective control of pain management is recommended which instills in patients a better confidence towards the doctor
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
DEFINITION
bull Pain (algesia) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
bull Odontogenic pain is caused by physical stimuli or the release of inflammatory mediators
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
106
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Pain is often associated with
Chronic inflammation
Bacterial by-products
Influx of immune cells and activation of the cytokine network and
Other inflammatory mediators
Teeth are innervated by Aδ and C neurons and the dual mechanism operating through Aδ processes most likely operates in the trigeminal nuclei However there is often branching of peripheral nerve processes to adjacent teeth and considerable convergence of primary sensory neurons on to thalamic projection neurons in the trigeminal sensory nuclear complex
DENTAL PAIN
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
ANALGESICS
DEFINITION A drug that selectively relieves pain by acting
on the CNS or on peripheral pain mechanisms without significantly altering consciousness
bull Analgesics are common pain relieversbull Many analgesics have anti-pyretic property and anti-inflammatory
properties
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CLASSIFICATION
Non-opioid analgesics(NSAIDS) Opioid analgesics
Non-selective COX Inhibitors
Preferential COX-2 Inhibitors
Selective COX-2 Inhibitors
Analgesic ndashantipyretics with poor antiinflammatory Action
Natural opioids
Semi-synthetic opioids
Synthetic opioids
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
How does one select the most effective analgesic
Severity of pain Past history of pain Any analgesic regimen should include a non-opioid
drug even if pain is severe enough to require the addition of an opioid
Pharmacologic management of mild to moderate dental and orofacial pain should begin with a non-opioid analgesic
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
NSAIDS
Inhibition of one or more components of the inflammatory response
Differ from the opioids in that there is a ceiling effect on their analgesic response
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
MECHANISM OF ACTION of NSAIDs
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CLASSIFICATION OF NSAIDs Non-selective COX Inhibitors
Preferential COX 2 Inhibitors
Selective COX 2 Inhibitors
Analgesic -antipyretic but poorAnti-inflammatory
Salicylates Aspirin
Pyrazolone Derivatives Phenylbutazone
Indole derivatives Indomethacin
Propionic acid derivatives Ibuprofen Naproxen
Anthranilic acid Derivative Mefenamic acid
Aryl Acetic acid Derivative Diclofenac
Oxicams Piroxicam
Pyrole pyrole derivative Ketorolac
Nimesulide
Meloxicam
Nabumetone
1Phenol derivative Acetaminophen (Paracetamol)
2PyrazoloneDerivative(Dipyrone)
Celecoxib
Rofecoxib
Valdecoxib
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Aspirin
salicylic acid Inhibits COX irreversibly Prevention of prostaglandin mediated
sensitization Analgesic dose ndash 600 mg tid
Side effectsbull Inhibits platelet aggregation bull Induces asthma by inhibition of prostaglandinbull Hypersensitivity - salicylismbull Aspirin use in children has declined since the
1970rsquos after reports of its association with Reyersquos hepatic encephalopathy (Reyersquos syndrome)
Precaution bull Avoided in diabetics heart
failure and pregnantbull Contraindicated with oral anti
coagulants(warfarin)bull stop 1 week before elective
surgeryUses Analgesic anti-pyretic and anti-
inflammatory First drug to be used in acute
rheumatic fever and arthritis Local application as a
keratolytic fungistatic and anti-septic
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Ibuprofen
bull Ibuprofen is used as an anti-pyretic in pediatric practice
bull Better tolerated alternative to aspirinSide effects Milder than aspirin Should be avoided in patients who have
asthma bleeding disorders gastric ulcers or surgical bleeding
CI ndash pregnancy peptic ulcerDose ndash 400 ndash 800 mg tds Rated as the safest conventional NSAID by the
adverse drug reaction reporting system (UK)
Ibuprofen the primary NSAID used in pediatrics is well tolerated even after over-dose
Ibuprofen also modestly suppresses swelling after surgical procedure
This provides additional therapeutic advantage without the potential liabilities of using steroids
This makes ibuprofen the drug of choice for controlling pain in most patients
Equally or more efficacious than aspirin 650mg+codeine 60mg
in relieving dental surgery pain
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
INDOMETHACIN
Potent anti-inflammatory drug with prompt antipyretic action
Used in conditions requiring prominent anti-inflammatory actions
Prominent adverse effects on CNS and gastrointestine
25-50 mg qid
Used in post-operative inflammatory conditions
Side effects Epigastric pain nausea headache Gastric ulceration and bleeding especially when combined with misoprostol
Dosage 50 mg 8 hrly
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
PARACETAMOL ( ACETAMINOPHEN) One of the most commonly used drug Prominent antipyretic effect Central analgesic action Weak peripheral anti-inflammatory
component Poor ability to inhibit COX in presence of
peroxides Children le 44kg
10 15mgkg every 4 6 hours max = 26 gday‑ ‑ Supplied as Drops80mg08ml calibrated dropper Suspension160mg5ml Chewable tabs80mgtabs Tablets 325mg - 500mg
In contrast to aspirin paracetamol does not stimulate respiration and has insignificant gastric irritation
Paracetamol does not affect platelet function or clotting factors
Acetaminophen overdose occurs after ingesting as little as 120 mgkg and should be treated with NAC (N-acetylcysteine) at a dose of 70 mgkg every 4 hours as early as possible
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
COXIBS1st Generation
Celecoxib Rofecoxib
2nd Generation
Valdecoxib Parecoxib Etoricoxib Lumaricoxib
Uses of COX Inhibitiors
COX-2
Reduce inflammation
Reduce pain
Reduce fever
NSAIDs anti-plateletmdashdecreases ability of blood to clot
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Combination analgesics
Rationale1 Multiple sites of action targets multiple
pain pathways
2 Potentially synergistic effect
Eg
bull Aspirin + acetaminophen
bull Ibuprofen + acetaminophen
bull Caffeine + acetaminophen
bull Ibuprofen + caffeine
bull NSAIDsacetaminophen + opioids
bull Analgesic + sedative
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Drug interactions of NSAIDs
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Toxicities due to PG synthesis inhibition
bull Analgesiabull Antipyresisbull Anti-inflammatorybull Anti-thrombotic
121
1 Gastric mucosal damage
2 Bleeding inhibition of platelet
function
3 Limitation of renal blood flow
4 Delay Prolongation of labour
5 Premature ductus arteriosus
closure
6 Asthma amp anaphylactoid
reactions in susceptible
individuals
Beneficiary actions due to PG synthesis inhibition
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Limitations of NSAIDs
Delayed onset of orally administered NSAID
Inability to relieve severe pain consistently
Apparent lack of effectiveness when given repeatedly for chronic pain
Most NSAIDs commonly used in dentistry have gastric irritation and inhibition of platelet aggregation as adverse effects
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
OPIOIDS
Obtained from Papaver somniferum
bull Opiod is the term used for drugs with ldquomorphine-likerdquo reactions
bull They were earlier called as narcotic analgesics
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CLASSIFICATION OF OPIOIDS
Natural opium alkaloidsbull Morphinebull Codeine
Semi-synthetic opiatesbull Heroin (diacetyl
morphine)bull Pholcodeine
Synthetic opioidsbull Pethidine
Fentanyl Methadone
bull Dextro propoxyphene Tramadol
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Mechanism Of Action of Opioids
125
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
MORPHINE
bull Specific depressant and stimulant in CNS
bull Poorly localized visceral pain relieved better than sharply defined somatic pain
bull Depresses respiratory centers
bull High first pass metabolism
bull Plasma t12 rarr 2-3 hrs
bull Doses ndash 10 -15 mg imsc
bull Morphine abuse is higher among medical and paramedical personnel
bull Side effects ndash sedation constipation respiratory depression
Antidote ndash Naloxone 04-08 mg iv repeated every 2-3 mins
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Therapeutic uses Mood and subjective effects ldquoEuphoricrdquo anxiolytic for
patients in pain
Morphine has a ldquoCalmingrdquo effect- loss of apprehension feeling of detachment lack of initiative mental crowding and inability to concentrate
Analgesia
Opioids induce sleep ndash can be used to supplement the sleep inducing properties of benzodiazepines
Treatment of diarrhoea
Relief of cough
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
CODEINE
Less potent than morphine Codeine is metabolized in part to morphine
which is believed to account for its analgesic effect
Used for mild to moderate pain and for antitussive effects
60 mg codeine ge 600 mg aspirin
side effect ndash constipation Abuse liability is lower than that of morphine
Can be taken for relatively longer period of time as less risk of physical dependence
PROPOXYPHENE
bull Half as potent as codeine
bull Abuse liability is lower than codeine
bull Combination with aspirin and paracetamol is supra-additive
bull Doses ndash 60-120 mg tid
Codeine + acetaminophen commonly used for relieving pain of pulpal origin
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Opioids uses in pain of pulpal origin
First line of drugs for
relief of pulpal pain
Also as adjuvants
when additional
pain control is
required
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Abuse liability of opioids
Exaggerated fear of ldquoaddictingrdquo patients exists
Physical dependance on opioids are a consequence of long term medical use
Such long term use is not prevalent for managing pain of pulpal origin
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Drug interactions of opioids
Opioid + CNS depressant supra-additive
Opioid + phenothiazine increased respiratory depression
Tricyclic antidepressant + opioid increased hypotension
Local anaesthetic + opioid safe ( however large doses have supra-additive effect)
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Withdrawal ReactionsAcute Action
bull Analgesiabull Respiratory Depressionbull Euphoriabull Relaxation and sleepbull Tranquilizationbull Decreased blood pressurebull Constipationbull Pupillary constrictionbull Hypothermiabull Drying of secretionsbull Reduced sex drivebull Flushed and warm skin
Withdrawl Sign
bull Pain and irritabilitybull Hyperventilationbull Dysphoria and depressionbull Restlessness and insomniabull Fearfulness and hostilitybull Increased blood pressurebull Diarrhoeabull Pupillary dilationbull Hyperthermiabull Lacrimation runny nosebull Spontaneous ejaculationbull Chilliness and ldquogoosefleshrdquo
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Side Effects of opiods
Short termbull Dulling of Painbull Euphoriabull Slow Nervous system bull Slowed heart ratebull Loss of cough reflexbull Nauseabull Overdoses can lead to deathbull Possibility of strokebull Overall slowdown of
biological systems
Long Termbull Addiction and very strong
withdrawal effectsbull Constipationbull Loss of libidobull Disruptions in menstruationbull ldquoCross-tolerancerdquobull Loss of appetitebull Problems associated with
buying street drugs ie sharing needles AIDS and prostitution
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
OTHER DRUGS WITH ANALGESIC EFFECT
134
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
bull Corticosteroids comprise glucocorticoids and mineral corticoids
bull The adrenal cortex produces approximately 10mgday of cortisol in the non-stressed adult Under severe stress this level may be increased more than 10 fold
MOA of steroids
interfere in arachidonic acid metabolism
a decrease in the release of vasoactive and chemo attractive factors
Decrease the secretion of lipolytic and proteolytic enzymes
decreased extravasation of leukocytes to areas of tissue injury
Thus the pharmacological effects of glucocorticoids oppose many of the inflammatory processes that are known to occur during periapical inflammation
STERIODS
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Steroids in endodontics
Glucocorticoids have been used
1 as a pulp-capping agent
2 as an intracanal medicament either alone or in combination with antibiotics and systemically as a means to decrease pain and inflammation
CI - Peptic ulcer Heart disease Diabetes Osteoporosis Glaucoma
bull Routes amp Dosagesbull If a systemic steroid is to be
administered an intra-oral IM injection or an intraosseous injection would be preferable over an extra-oral IM injection
bull A dose of 6ndash8mg of dexamethasone or 40mg of methylprednisolone has been used
bull If an oral route is chosen 48mg
methylprednisoloneday for 3days and followed by 10ndash12mg dexamethasoneday for 3 days should provide significant post treatment pain relief
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Procedurecondition Initial choice If severe
i Apical periodontitis
ii Canal debridement
iii Overfillingincomplete debridement
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
iv Periapical or amputational surgery with minimal trauma
Aspirin or other NSAIDsEg Ibuprofen 200-400mg orDiclofenac sodium 50mg
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
v Extensive surgery with considerable trauma
Aspirin or other NSAIDEg Ibuprofen 200-400mg orDiclofenac sodium 50mgPreferably pre-op loading dose
NSAIDs
Ibuprofen or diclofenac sodium 600-800mg 50-75mg or valdecoxib 40 mg
Suggested analgesics for endodontic proceduresconditions
Ibuprofen or diclofenac sodium 400-600mg 50-75mg or valdecoxib 20-40 mg
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
During InterventionPreoperative
Pain
Post-Operative
PAIN CONTROL STRATEGY
138
Oral Sedation
Preoperative Analgesics
bull IV Sedation
bull Nitrous Oxide
bull Local Anesthesia
bull Analgesic Prescriptionbull Opioids bull Non-opioids
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Anti-inflammatory drugChymoral
Anti-inflammatory drugsMucolytic (breaks down bronchial secretion)Anti-exudate (reduces swelling)
Used as an adjuvant for oro-dental infections in children Should be taken only on empty stomach or 1hr bfr meal Administered by oral route Dosage 5-12 yrs 1 gastro-resistant tablet tid Recommended dose given 48 hrs before surgery No known clinically significant interactions Side effects very rarely GI upset and allergic manifestations
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Conclusion
Better understanding of pulpal pain mechanism and pharmacotherapy of pain
enables the pedodontist to manage different pain conditions effectively thus reducing public dental phobia in children
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Prescription includes
bullSuperscription- Date the name address and age of the patient and the
symbol Rx
bullInscription - body of the prescription containing the name and amount or
strength of each ingredient
bullSubscription - The directions to the pharmacist usually consisting of a short
sentence such as make a solutionldquo
mix and place into 10 capsules
dispense 10 tablets
bullSignatura- From the Latin signaldquo contains the directions to the patient
take as directedrdquo ldquoavoidedrdquo
bullDoctorrsquos signature
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
Table 1 Common Terms and Abbreviations
Term or Phrase Abbreviation Meaning
ante cibos ac before meals
aqua aq water
bis in die bid twice a day
cum aqua cum aq with water
dispensa disp dispense
et et and
gutta guttae gtt drop drops
hora somni hs at bedtime
misce m mix
non repetatur non rep do not repeat
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
omni die od daily
omni mane om every morning
omni nocte on every night
per os po by mouth
placebo placebo to please
post cibos pc after meals
quantum sufficiat qs sufficient quantity
quater in die qid four times a day
recipe Rx take
si opus sit sos if necessary
ter in die tid three times a day
trochiscus torchisci troch lozenge lozenges
unguentum ungt ointment
ut dictum ut dict as directed
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
REFERENCES Pharmacology and Therapeutics in Dentistry
Yagiela Dowd Niedle 5th edition Endodontics John I Ingle Leif K Balkland 5th Edition Endodontics John I Ingle Leif K Balkland 6th Edition Essentials of Medical Pharmacology KD Tripathi
5th edition Katzung basic and clinical Pharmacology 9th
edition Pathways Of The pulp Stephen CohenKenneth M
Hargreaves9th edition
147
THANK YOU
147
THANK YOU