Best_Pharmacology-dentistry.pdf

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Practical Review of Pharmacologyfor Dentistry

Michigan Dental Association Annual SessionMay 3, 2014

Joseph A. Best, D.D.S., Ph.D.Assistant ProfessorDivision of Oral and Maxillofacial SurgeryMarquette University School of Dentistry

Private PracticeOral and Maxillofacial Surgery Associates Ltd

Waukesha*Waukesha*Oconomowoc*Mukwonago*Johnson Creek


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Practical Review of Pharmacology for Dentistry J.A. Best1

Understanding Pain

The dental team as pain specialists Developing pain control strategies based on an understanding of the basic science If you only use one local anesthetic and one analgesic and no adjunctive techniques, you are not

reaching your potential in pain control

Highly variable Strong emotional component Complex neurologic pathways involved with both peripheral and central components

Basic pain pathwayInflammation and pain


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Why does this matter?

Inflammatory mediatorsActivate/sensitize nerve terminalsIncrease in spontaneous activityDecrease in threshold

Hyperalgesia

Once tissue injury occurs, a cascade of events occurs that produces a heightened responsiveness of theinjured and surrounding tissue termed hyperalgesia

The hot tooth

The Big picture

Understanding the pathways of pain and where in the pathway your management strategies aretargeting

Can we target at more than one level and is this a more effective pain control strategy Local Anesthetics How do local anesthetics work Prevent the generation and propagation of nerve action potentials Blocking the sodium channel to prevent sodium influx

Local Anesthetics

How do local anesthetics work

Prevent the generation and propagation of nerve action potentials Blocking the sodium channel to prevent sodium influx

To be effective, local anesthetics must penetrate the nerve because it is thought that they blocksodium conduction from the inside

pKa helps determine how well an anesthetic can penetrate a nerve


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Why is the pKa of a local anesthetic important?

To be effective, local anesthetics must penetrate the nerve pKa helps determine how well an anesthetic can penetrate a nerve

Inflamed tissues tend to have decreased pH, therefore there is a tendency for local anesthetics tobe in the charged (hydrophilic) form pKa determines the % of molecules that are charged

pKa of selective agentsMepivacaine 7.6Lidocaine 7.7Articaine 7.8Etidocaine 7.9Prilocaine 7.9Bupivacaine 8.1Procaine 9.1

We also must consider nerve anatomy

Onset of Action

Time from when anesthetic is delivered to when pulpal anesthesia is achieved (Induction time) Effected by:

Concentration of anestheticpH of the tissues to be anesthetizedpKa of the anestheticThickness of the tissue and size of the nerveBlood supply to the areaPotency of the anesthetic

Duration of Action Time during which the patient has pulpal anesthesia

Blood supply to the areaDegree of protein bindingVasodilating activity of the agentVasoconstrictor activityPatient to patient variability

Toxicity

Remember that local anesthetics are non-selectiveo Can interfere with impulse conduction in any body system

CNS PNS Muscle (skeletal, cardiac, smooth)

More likely to occur with topical agents and in pediatric (or small) patients Toxicity

o Dose dependent Prevent systemic toxicity by good technique

o Aspirationo Careful dosingo Being aware of medical considerations


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o Being aware of drug interactions

Methemoglobinemia

Local anesthetic metabolites can sometimes oxidate hemoglobin to methemoglobin in susceptibleindividuals

Patient presents with cyanosis (blue lips, nail beds) that does not improve with oxygen Rarely fatal Seen with prilocaine (Citanest), articane (Septocaine) and the topical agent benzocaine Treated with intravenous methylene blue

Allergy

Patient reports of local anesthetic allergy are fairly common TRUE local anesthetic allergies are exceedingly rare Be VERY careful NOT to tell a patient that they have an allergy to a local anesthetic if they simply

have a bad experience (syncope, palpations, anxiety attack)Esters

Esters more commonly cause allergy as a result of the formation ofp-aminobenzoic acidIf allergic to an ester, the patient is allergic to all esters

AmidesMost investigators consider amides essentially non-allergicAnesthesiol Rev3:13-16, 1976If concerned about allergy to one amide, it is ok to try another (no cross-reactivity)Epinephrine

It is inconsistent with life to be allergic to epinephrine, it is simply impossible

What if someone has a true local anesthetic allergy?Options?-Confirm with allergist-Infiltrate with 50 mg of benadryl (diphenhydramine)-Oral sedation and nitrous oxide-I.V. sedation or general anesthetic

Metabisulfites

Used in local anesthetics with vasoconstrictor Evidence that certain patients (mostly asthmatics) can be hyper-reactive to sulfites that are inhaled

or ingested but usually not injected Probably not immunologic in nature If very severe asthmatics or persons with metabisulfite allergy, better to avoid local with

vasoconstrictors There is NO contraindication to the use of local anesthetics which contain metabisulfite in patients

with a history of allergy to sulfonamide antibiotics (so called sulfa allergy)

Methylparaben

NOT AN ISSUE FOR DENTISTS! Only used as a preservative in multi-dose vials

No longer used in dental single-use packaging

Malignant Hyperthermia (MH)

Previously thought to be induced by local anesthetics NO EVIDENCE in the literature to support this view It is now considered safe to use all commercially available local anesthetics in patients with a

history of MHJ Can Dent Assoc 68:546-51 2002

Metabolism


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Amide

Metabolized in the liverEsters

Metabolized by plasma pseudocholinesterasesPara-aminobutyric acid is a metabolite (allergen)

Liver disease and local anesthesia

Does not effect duration of local anesthetic (remember what determines duration of action) Only important with significant liver disease Best to limit dosing (quadrant dentistry) when dealing with patients with severe liver disease Also important for esters since plasma pseudocholinesterases are synthesized in the liver

VasoconstrictorsWhy?

Prolong durationAntagonize vasodilation of local anestheticsDecrease bleeding

Decrease systemic toxicityHow?

Alpha-1 agonistsProduces vasoconstrictionAgents

EpinephrineLevonordefrin (Neo-Cobefrin)

Possibly less cardiac and pressor side effects than epinephrine

NorepinephrineSympathomimetics

Activate the sympathetic nervous system

VasoconstrictorsContraindications

Untreated pheochromocytomaUncontrolled or unstable anginaUncontrolled hyperthyroidismMI within last 6 mo.

Use with caution (limit use of epinephrine to 0.04 mg, 2 carpules of 1:100,000)

Moderate to severe cardiovascular diseaseCVA historyModerate to severe hypertension

Adverse reactions to vasoconstrictorsLow dose epinephrine

Can produce syncope-like symptomsHigh dose epinephrine

Palpitations

Low Dose Epinephrine


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Increased PP

Decreased DBPHigh Dose Epinephrine

Increased PP

Increased DBP, SBP

Specific Local AnestheticsSelection of anesthetic is based upon

Patient medical historyDuration of action desiredNeed for vasoconstrictorClinical situation (i.e. active infection)Availability

Vasoconstrictor drug interactionsBeta-blockers

Nonselective blockers like propranolol, nadolol and timolol can cause an increased alpha response fromsystemic epi dose resulting in systemic vasoconstriction with increased BP

Not a problem with selective blockers like atenolol, metoprolol, acebutolol, betaxolol

Adrenergic ReceptorsAlpha 1

Constriction arterioles and veinsBeta 1

Heart: increased rate, contractility, conduction and automaticityBeta 2

Trachea and Bronchiole relaxationArteriole and vein dilation (except skin and brain)

Patient on Non-selective Beta-BlockerAlpha 1




Patient on Cardio-selective Beta-BlockerAlpha 1





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lidocaine(Xylocaine, Alphacaine, Lignospan, Octocaine)

Class: Amide Onset: 2-4 min Duration: 60-120 min (180-240 with epi)

Max dose: 4.4 mg/kg Available as: 2.0% +/- 1:100,000 or 1:50,000 (36 mg per 1.8 cc) Also available without epi (not very effective due to very short duration) Popular for a reason: cheap, effective and safe

bupivacaine(Marcaine, Sensorcaine)

Class: Amide Onset: 2-10 min Duration: 240-540 min Max dose: 1.3 mg/kg Available as:

0.5% +/- 1:200,000 epinephrine(9 mg per 1.8 cc) May not be ideal for pediatric patients Great for procedures with significant post-operative pain (3rd molars)

mepivacaine(Carbocaine, Polocaine, Isocaine, Scandonest)

Class: Amide Onset: rapid 1-2 min Duration: 120-180 min Max dose: 4.4 mg/kg Available as: 3.0% without vasoconstrictor 2.0% with1:20,000 neo-cobefrin (120-240 min duration) Nice drug for cardiovascular compromised (less vasodilating) patients and infected tissues (pKa

7.6)prilocaine(Citanest)

Class: Amide Onset: rapid 2-5 min Duration: 100-240 min (120-240+epi) Max dose: 6 mg/kg Available as: 4.0% without epi 4.0% (Citanest Forte) with 1:200,000 epi Methemoglobinemia

etidocaine

(Duranest) Class: Amide Onset: rapid 2-3 min Duration: 240-540 min (+epi) Max dose: 6 mg/kg Available as: 1.5% without epi 1.5% with 1:200,000 epi Long duration with relatively quick onset


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No longer available in U.S.

articaine(Ultracaine, Septocaine)

Class: Amide Onset: rapid 2-3 min

Duration: 180-300 min (+epi) Max dose: 7 mg/kg Available as: 4% with 1:100,000 or 1:200,000 epi Claims of better soft-tissue and hard-tissue diffusion Contraindicated in patients with Sulfa allergy??? Methemoglobinemia/ neurotoxicity questions?

Evidence for articaine over lidocaine?EFFICACY OF ARTICAINE: A NEW AMIDE LOCAL ANESTHETICStanley F. Malamed, D.D.S.;Suzanne Gagnon, M.D.; Dominique LeBlanc, D.Pharm JADA, Vol. 131, May 2000, Pgs. 635-642ABSTRACTIn three identical randomized, double-blind, multicenter studies, the authors compared thesafety and efficacy of articaine 4% with epinephrine 1:100,000 to lidocaine 2% with epinephrine

1:100,000. A total of 1,325 subjects, ages 4 to 80 years old were treated for simple or complex dentalprocedures and received either articaine 4% with epinephrine 1:100,000 or lidocaine 2% with epinephrine1:100,000. The subjects were randomly selected in a 2:1 ratio to receive articaine (882 subjects) orlidocaine (443 subjects). The authors found that articaine 4% with epinephrine 1:100,000 providedclinically effective pain control during most dental procedures and was well tolerated by the 882 subjectsreceiving it. The onset and duration of anesthesia compared favorably with other available dentalanesthetics.

Cost2% Lidocaine with 1:100,000 epi

1 can (50 carp) $23.951 case (500 carp) $229.504% Septocaine with 1:100,000 epi

1 can (50 carp) $39.751 case (500 carp) $377.50The onset and duration of anesthesia compared favorably with other available dental anesthetics.

articaine and neural toxicityGoogle search Septocaine

First hit: Septocaine LawyerEvidence:

In laboratory studies articaine found to be neurotoxicClinically has been associated with slight increase in nerve injuryInt J Oral Maxillofac Surg.2006 May;35(5):437-43. Epub 2005 Dec 15: J Can Dent Assoc.1995 Apr;61(4):319-20, 323-6, 329-30.Incidence very low (1:785,000)

Application of Articaine- Avoid as primary drug for IAN blocks?- Great for minor procedures for maxillary infiltration to avoid palatal injection- Pediatric patients for all maxillary extractions to avoid palatal injections- Lower anterior central incisors- Back-up for failed blocks

If using articaine for blocks- Be sure to document any zingers


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o Physical interaction of the needle with the lingual or inferior alveolar nerveo When this happens either remove the needle or move the needle without injection, do not

want to inject anesthetic into the structure of the perineurium- ballooning the nerve leads to bad outcomes including permanent anesthesia or worse

Topical agents

Benzocaine (Hurricane) topical gelo 20% benzocaineo Usually approximately 9 mg per doseo methemoglobinemia

Benzocaine topical sprayo 50 mg benzocaine per metered sprayo methemoglobinemia

Tetracaine (Cetacaine) REMEMBER: these are ester anesthetics

Topical Agents

Lidocaine Patch Lioderm (5%)

Neuropathic painTMD applications ( other transdermal medication for TMD) ?

Duration of Pulpal anesthesia2% Lidocaine without epi 10 min3% Mepivacaine without epi 40 min3% Prilocaine without epi 60 min2% Lidocaine with 1:100,000 epi 60 min4% Articaine with 1:100,000 epi 75 min0.5% Bupivacaine with 1:200,000 epi >90 min0.5% Etidocaine with 1:200,000 epi >90 min

Relative vasodilating effects

Prilocaine 0.5Mepivacaine 0.8Articaine 1Lidocaine 1Bupivacaine 2.5Etidocaine 2.5

Dealing with Anesthetic Failures

Managing the hot tooth

Understanding pH and local anesthesiaUnderstanding hyperalgesiaWhen is it better to localize, give antibiotics and let things cool down?

Consider conscious sedationPatient variation

Is it wrong to assume that all anesthetics are equipotent in all patients?There are no drugs that do not have a bell-shaped response to drug therapyHave a plan

A secondary delivery techniqueGow-Gates and field blocksPDLIntraosseous techniques


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Abort procedure in elective situations

Evaluate the anatomyPanorex, clinical exam

Is sedation an option?Patience

We generally do not allow enough time for local to work, especially for profound pulpal anesthesiaPatients with low pain thresholds and anxiety

Remember the central nervous system links to pain perceptionAnxiety control measures significantly augment pain management

Local anesthetic adjunct equipment

PDL injections

Liga-jet Local anesthetic warmers Computerized injection wands Counter-pressure devices Intra-osseous injection devices

Intraosseous TechniquesDifferent systemsSuccess

Primary technique45-93% effective with short duration

Supplemental technique80-90% effective with longer durationVasoconstrictor

40-100% patients with increased HR

Analgesic Strategies

Classes of AnalgesicsNon-opioid analgesics

SalicylatesNonsteroidal anti-inflammatory drugs (NSAIDs)AcetaminophenPeripherally actingOpioid analgesics

AgonistsMixed agonist-antagonistCentrally acting

Non-opioid analgesics (NSAIDs)

Excellent oral efficacy Relatively low incidence of side-effects Low abuse potential Low cost First line drugs for post-operative dental pain


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NSAIDS: Mechanism of actionCyclo-oxygenase (two isoforms)

COX-1 ubiquitous, formed in normal quiescent

COX-2 inducible form expressed in cells after trauma

role in inflammation

COX selectivityCox-2 selective agents

These agents are likely to have fewer G.I., renal, and platelet related side effects Expensive Acute vs. Chronic pain Excellent dosing schedules Same contraindications as other NSAIDs Increased risk for stroke or M.I.

JAMA 2001 Aug 22-29;286(8):954-9

Cox-2 selective agents

Vioxx (rofecoxib) off the market Celebrex (celecoxib) Bextra (valdecoxib) off the market Prexige (lumiracoxib) Not approved in US Arcoxia (etoricoxib) FDA approval application withdrawn Mobic (meloxicam) Parecoxib (injectable prodrug of valdecoxib) Cox-189


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Cox-3

Splice variant of Cox-1 in mice Human? Involved with fever mechanism Site of acetaminophen activity Cross reactive with Cox-1 inhibition

Therapeutic role/use unknown PNAS | October 15, 2002 | vol. 99 | no. 21 | 13926-13931

Salicylates

Aspirin650 mg q 4 hoursMild pain

Diflunisal (Dolubid) Longer half-life, slow onset 1000 mg load then 500 mg BID Equipotent to Tylenol #3 Adverse reactions

G.I. upsetInhibition of platelet functionContraindications

History of allergyPeptic ulcer diseaseSevere AsthmaticsPregnancy (Dolubid)Children with influenza or chicken pox (Reyes syndrome)Patients on coumadinRenal diseaseLiver disease

Proprionic acids

Ibuprofen (Motrin, Advil, others)o 400-800 mg Q 4-6 hours

Ketoprofen (Orudis, Actron)o 50-75 mg Q 8 hours

Flurbiprofen (Ansaid)o 50-150 mg Q 8 hours

Fenoprofen (Nalfon)o 200-600 mg Q 8 hours

Naproxen (Naprosyn)o 250-500 mg Q 12 hours

Oxaprozin (Daypro)o 1200 mg Q day

Adverse reactions

G.I. upsetInhibition of platelet functionContraindications

History of allergy to aspirin or NSAIDsPeptic ulcer diseaseSevere AsthmaticsPregnancyLiver diseaseRenal disease


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IndoleEtodolac (Lodine)

More Cox-2 selective?Has been shown to be an effective analgesic in dental pain models

Heteroaryl acetic acids

Ketorolac (Toradol)

Can be given parenterallyExpensive orallyRole in dentistry?Para-aminophenol

acetaminophen (Tylenol)

Weak anti-inflammatory Analgesic/anti-pyretic

OpioidsAgonists

codeine hydrocodone (Vicodin) hydromorphone (Dilaudid) meperidine (Demerol) methadone (Dolophine) Morphine (MS Contin) oxycodone (Percodan, Percocet) propoxyphene (Darvon, Darvocet) tramadol (Ultram)*

tramadol (Ultram)Mechanism of action

Weak opioid agonist

Serotonin/NE reuptake inhibitor100 mg = two Tylenol #3 in dental pain studyDosage 50-100 mg Q 4-6 hoursCannot be used in patients with seizure historyExcellent in patients with long list of drug sensitivitiesAlso available in combination with acetaminophen (Ultracet)

OpioidsMixed agonist/antagonist

pentazocine (Talwin) Less mu effectspentazocine + naloxone (Talwin Nx)nalbuphine (Nubaine)Antagonistnaloxone (Narcan)naltrexone (Trexan)

Analgesic Strategy

Indication NSAID Opioid

Mild pain ibuprofen 400-600 mg Q.I.D. tramadol 50 mg T..I.D.


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naproxen 200-400 mg T.I.D.etodolac 200-300 mg T.I.D.

Moderate pain ibuprofen 600-800 mg Q.I.D. hydrocodone 5 mg,naproxen 300-400 mg T.I.D. Tylenol 325 mg Q4hetodolac 300-400 mg T.I.D pentazocine 50 mg

Severe pain ibuprofen 800 mg Q.I.D. hydrocodone 7.5-10 mg,naproxen 500 mg T.I.D. Tylenol 325 mg Q4hetodolac 400 mg T.I.D

NSAID Cost

NSAID Frequency Cost/dayNNaapprrooxxeenn555500mmgg BBIIDD $$00..6644

Ibuprofen 600 mg QID $1.27Etodolac 400 mg BID $1.36Diclofenac 50 mg BID $1.69Ketoprofen SR 200 mg QD $1.97Diclofenac ER 100 mg QD $2.91Ketoprofen 75 mg QID $3.39Ketorolac 10 mg QID $3.46Celecoxib 100 mg BID $4.56Rofecoxib 50 mg QD $4.74

Whats NewNew Cox-2 or Cox-3 Selective AgentsNK1 receptor antagonists (block substance P)

CP-99,994Opiates in anesthetics?

Articaine with epinephrine and morphine (inflammation)Caffeine as an additive

Synalgos DC (dihydrocodone, aspirin, caffeine combination)Panlor DCNociceptine/Orphan FQ

New opioid peptide and receptorUltra-long acting local anesthetics

Preemptive analgesiaPrevent the formation of proinflammatory cytokines before they are established

NSAID premedicationSteroidsSignificant evidence in both medical and dental literature supporting the use of presurgical anti-inflammatory medications to decrease post-operative painBleeding is not an issueThis strategy should also include the use of long-acting local anesthetics (Marcaine/Duranest)


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Nausea and VomitingGood post operative instructions are the best way to prevent this complicationMechanism

Stimulation of the chemoreceptor trigger zone in the medullaVestibular component (ambulatory vs. recumbent patients)Treatment

Stop taking the opiate analgesicChange to a less nausea provoking medicationHave the patient lay stillAntiemetics

AntiemeticsPhenothiazines (dopamine antagonists)

Phenergan (promethazine) 12.5-50 mg q 4-6Compazine (prochlorperazine) 5-10 mg tidZofran ODT (ondansetron)

5-HT3 (serotonin) receptor blockerOral Dissolvable Tablet (ODT)Adult dose 16 mg ODT tablets 1 hour prior to anesthesiaexpensive

Oral SedationIts nothing personal doctor, but I hate dentists.

Between 6% to 14% of the U.S. population are estimated to VOLUNTARILY avoid dental carebecause of anxiety (Milgrom P et al. Treating fearful dental patients, Reston VA, 1985, RestonPublishing)

The difficult patient

In a survey of dentists, 57% reported that the most stressful factor in dental practice is managing the

difficult patient (Kahn RL etal. Dentistry: What causes it to be a stressful profession?Int Rev ApplPsych29:307, 1980)

Can we do anything to help the anxious patient and at the same time help ourselves? Pain and Anxiety Anxiety is known to decrease a patients pain threshold (Pain: Clinical and Experimental Perspectives,

St. Louis, 1975, Mosby) Pain perception has a strong emotional component Controlling anxiety is critical in managing peri-operative pain


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Anxiety as a medical problem

It helps to think of dental phobia and anxiety as a medical diagnosis

Would you blame a diabetic for not being able to control their blood sugar?If your perspective toward a patient with anxiety is that the patient has a treatable medical problem, youmay find it easier to deal with the inherent difficulties in managing these patients.Anxiety and PainPharmacology, in the form of oral sedation, cannot replace good chair-side mannerAnxiety and Pain control in dentistry must be multi faceted and aimed at maximum patient comfort with

behavioral management, sedation, good local anesthesia and adequate post-operative analgesia

The Big pictureIf you control anxiety in your practice you will be better able to control painReducing anxiety with oral sedation can clearly improve pain control during dental proceduresAvoid the pain-anxiety paradox: Pain is a source of anxiety, anxiety is a factor that increases pain, andincreased pain incites further anxiety (Schottestraedt W. )Failing to control anxiety

Increases stress for the practitioner

Increases incidence for medical emergency situations

SyncopeAnginaHyperventilationBronchospasmAnxiety attacksIncrease appointment failure ratesWhen patients simply cannot be managed with local anesthetics alone

What are the options

Nitrous oxideOral SedationIntramuscular Sedation

Intravenous SedationGeneral Anesthesia

So you have a patient with significant anxiety, now what?Deciding on a management strategyDecision making based on

Level of anxietyMild-iatrosedation, nitrousModerate-oral sedation, nitrous, intramuscular, intravenousSevere-intravenous, general anesthesia

Coexisting diseaseASA scale

AgeBe careful with extremes of age (65)

Your level of training/experienceResidency v. weekend coursesACLS, BCLS, PALSStaff experience

Procedure to be preformedScaling v. full-bony impaction

The state of your office


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Are you prepared to deal with complications

Equipment for emergenciesOffice layout/infrastructureWhats the use of ACLSIf you dont.

Have equipment or know how to start an I.V.?Have equipment or know how to place an endotracheal tube?Delivery of ACLS protocols is dependent on both.

Defining termsFrom the ADA Guidelines for the use of Conscious Sedation, Deep Sedation, and General Anesthesia forDentistsAnalgesia- diminution or elimination of painAnxiolysis- diminution or elimination of anxietyLocal Anesthesia- elimination of sensation, in particular pain, in a localized area of the body by topicalapplication or regional injection of local anestheticConscious sedation- minimally depressed level of consciousness that retains the patients ability toindependently and continuously maintain an airway and respond appropriately to physical stimulation and

verbal command and that is produced by a pharmacologic or non-pharmacologic method or combinationthereof.Deep Sedation- an induced state of depressed consciousness accompanied by partial loss of protectivereflexes, including the inability to continually maintain an airway independently and/or respond

purposefully to physical stimulation or verbal command, and is produced by a pharmacological or non-pharmacological method or a combination thereof.General Anesthesia- an induced state of unconsciousness accompanied by partial or complete loss of

protective reflexes, including the inability to continually maintain an airway independently and respondpurposefully to physical stimulation or verbal command, and is produced by a pharmacological or non-pharmacological method or a combination thereof.What can a dentist without advanced training do safely?Without advanced training in either dental anesthesia, general practice residency or oral andmaxillofacial surgery, dentists should never intentionally take any patient beyond conscious sedationSkill in this area CANNOT be attained in a weekend or evening courseWhy?????

Its all about the airwayAirway managementIf you do not have the experience, ability and equipment to manage a patient that loses an airway, youhave no business taking people beyond conscious sedation

EquipmentLaryngoscopeEndotracheal tubes of various sizesOxygenLaryngeal mask airwaysNasal and oral airwaysBag-valve mask

Emergency surgical airway equipment

Airway ManagementTechnical skills required

Ability and experience maintaining an airwayAbility and experience in laryngoscopy and intubationAbility and experience in managing the difficulty airwayAbility and experience with providing a surgical airway if necessaryACLS: what is the use of being ACLS certified if you cannot start an I.V. or intubate someone!?


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Therefore the goal is..Anxiolysis

A controlled level of conscious sedation with minimal to no risk for patients to lose the ability to maintaina patent airwayIntentionally taking people to deeper levels of sedation without proper training or equipment is not

only cavalier it puts patients lives in jeopardyLow risk does not equal no risk!

The long and short.

Dentists can market sleep dentistry Dentists can imply that patients are asleep or sleep away the hours in comfort while your

dentistry is completed But in reality, to attempt to genuinely take patients to levels beyond anxiolysis/conscious sedation

without formal training is dangerous

What does this mean???

If you use oral sedation, and a patient genuinely does not respond at all to giving a local anestheticinjection, they are deeper than conscious sedation and the airway is potentially at risk

Remember: low risk does not equal no risk

Patient AssessmentASA ClassificationAmerican Society of Anesthesiologists

ASA I : normal healthy patient, no systemic diseaseASA II: mild systemic diseaseASA III: severe systemic disease that limits activityASA IV: Incapacitating systemic disease that is constant threat to lifeASA V: patient not expected to survive 24 hours without surgery

Assessment

Generally you want to limit yourself to providing oral sedation to ASA I and ASA II patientsYou especially want to be careful with patients that have

COPDCongestive heart failureAngina PectorisHeavy smokersModerate to severe asthmaticsPatients with significant cardiac or pulmonary disease

ASA IIIManaging these cases is a balancing act of risks

-Premium on pain and anxiety control-Want to avoid stress

-Can this be achieved with local only?-Nitrous oxide and/or valium can be potentially safer than local only or general anesthesia-Even I.V. sedation with versed is appropriate in some cases

Now what?Once you have assessed the patient

What level of anxiety control does the patient need?Local anesthesiaLocal anesthesia with oral sedationLocal anesthesia with nitrous oxide


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Local anesthesia with oral sedation and nitrous oxideIntravenous deep sedationGeneral anesthesia

Oral SedationAdvantages

SafeAlmost universally acceptedConvenientEconomicalLow incidence of adverse reactionsDecrease severity of adverse reactionsNo needles or syringes or specialized equipmentWhen done properly, it is well within the scope of a practicing general dentist without need for advancedresidency trainingDisadvantage

Requires a knowledge of pharmacologyPatient compliance

Slow onset/recoveryMore UnpredictableCannot titrate or tightly control (titration by appointment possible, but not without risk)Loss of some level of controlTitration within an appointment is potentially dangerous and is not recommended (intentional over-dose)Indications for Oral Sedation

Provide sedation and ensure a restful sleep during the night prior to anxiety provoking appointment To provide light levels of sedation for preoperative anxiety reduction To aid in the anxiety control just prior to utilizing other anesthesia techniques (I.V. sedation)Drugs used in oral sedationOpiates

Potent analgesic drugs

Rarely used for oral sedationSometimes used in combination with benzodiazepines, but should be done so with caution due to thepotential for deeper levels of sedation

Significant respiratory depression possible

Other drugs

Zolipen (Ambien)Sedative hypnotic used to treat insomniaOnly mildly anxiolytic

Chloral HydratePopular with pediatric dentistsUnpleasant tasteNo analgesic properties

AntihistaminesBarbiturates

Benzodiazepines

The most widely used oral agents for anxiolysis in dentistry Safe, effective, cheap Tolerated well orally Minimal hang-over Extremely effective antianxiety medications


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Wide therapeutic safety margin

Mechanism of ActionGABA receptors

Cerebral cortexLimbic system

Cerebellar cortexGlycine receptors

BrainstemSpinal cord

MetabolismPlasma protein boundMetabolized in the liver

OxidativeConjugationMetabolites can be pharmacologically active leading to longer half-lives for some agentsMetabolites excreted in the urine

Diazepam (Valium)Pharmacology

Insoluble in water (phlebitis)Large volume of distribution and low hepatic clearance

Organ effects

Decreased anxiety, sedation, hypnosis and amnesiaPotent anticonvulsantMild respiratory depressionMinimal cardiovascular effectsDecreases muscle tone

Clinical IndicationsPreoperative and intraoperative sedationManagement of anxiety disordersAcute alcohol withdrawalRelief of skeletal muscle spasmStatus epileptics

Contraindications

Glaucoma (acute narrow angle)Previous hypersensitivityPregnancy (first trimester)Administered with extreme care

ElderlyChildrenPatients with limited Pulmonary reserve

Adverse Reactions

Phlebitis (when given intravenous)CNS depressionconstipation, nausea, incontinence


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bradycardia, hypotensionblurred vision, diplopia, nystagmusuticariahiccupsparadoxical reactions

Dosage

Oral: 5-10 mg for 70 kg adult (decreased for elderly); 0.2 to 0.5 mg/kg for childrenMidazolam (Versed)

96% protein boundMetabolized in liver to active metabolites, one-tenth the potencyAbsorbed orally, 30-50% bioavailabilityElimination half-life of 2-2.5 hours

Midazolam (Versed)Organ effects

Decreased anxiety, sedation, hypnosis and amnesiaStable intracranial pressureMild respiratory depressionMinimal cardiovascular effectsDecreases muscle tone% protein bound, less lipid solubleMetabolized in liver to inactive metabolitesElimination half-life of 10-20 hoursClinical Indications

Preoperative and intraoperative sedationManagement of anxiety disordersAcute alcohol withdrawalRelief of skeletal muscle spasm

Status epileptics

Triazolam (Halcion)

Excellent oral sedative Good for the night before the appointment to help with sleep 0.125-0.25 mg one hour prior to appointment (Maximum 0.5mg) Use with caution in elderly patients Care when combining with nitrous in pediatric patients Excellent amnestic qualities

Sonata (zaleplon)

Non-benzodiazepine with benzodiazepine like effects Acts through GABA receptors Used to treat insomnia Some amnesia Dose 5-10 mg Not reversed by romazicon

Nitrous oxide and oral sedation


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When combined with oral sedative hypnotics the level of sedation achieved with nitrous oxide can besignificant

Care should be taken when combining oral and inhalational sedation techniques

Length of procedure

1 hour Sonata (zalepon)

2-3 hours Halcion (triazolam) 4 hours or more Ativan (lorazepam)

Problems with long appointmentsIn the OR, under general anesthesia

Great concern for development of deep venous thrombosis during procedures taking more than 2-3 hoursPneumatic stockings are used to prevent thisIn the dental chair

What precautions need to be taken for long procedures?Unknown.

ConsentAll consent must be obtained prior to patient taking any sedative/hypnotic drug.

Office preparationMust be prepared for a medical emergency

Oxygen with appropriate delivery devicesBag-valve maskRebreather maskNasal cannula

Emergency medical kit

RecoveryPatients may need to stay in the office for an extended period of time to become ambulatory prior todischarge

Additional equipment

Automatic blood pressure cuff Pulse oximeter When to monitor

Medically compromised patientsMulti-drug oral sedationsCombination of oral sedative with nitrous oxide

Instructions to patientsPatients must be escorted to and from the office by a responsible adult

Escort should stay in the officePublic transportaion?Patients should generally take the oral premedication on a relatively empty stomach (faster and more

predictable uptake)Patients need to understand the level of sedation expected

ComplicationsNausea and vomiting

Very rare with oral sedationSedation level not adequate

Increase dose for next appointment


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Giving a second dose of the sedative on the same day is controversial and not recommendedIs the patient a candidate for oral sedation?Over sedation

When using recommended doses, this is rareUsually can be managed by simply monitoring the patientDecrease dose at next visitBe prepared to provide oxygen if necessaryComplicationsAllergic reactions

Very rareShould be prepared for this with emergency kitIdiosyncratic reactions

Removal of inhibitionCrying, semi-uncooperativeSeen much more frequently with I.V. benzodiazepinesTreated with monitoring and avoiding the medication in the futureReversal if available

Benzodiazepine reversalFlumazenil (Romazicon)

This is an I.V. drugUnless you know how to start an I.V., this may not be an optionI.M. use of flumazenil has not been studied in humans (off label use)What dose?Where?How?1/2 life vs. benzodiazepine given

Pediatric patients

Not small adults Diminished pulmonary reserve Small airway

Can desaturate very rapidly Need to be managed very carefully Under the age of 13, best managed by practitioners with advanced training

Final thoughts on sedationExpanded scope of anesthesia requires

Efforts to clearly understand the drugs you are usingComfort in managing the potential complicationsGoal for general dentist or specialist without advanced anesthesia training should by anxiolytic conscioussedationConsider referral or hospital affiliation for patients needing anesthesia scope outside of your expertise

Big picture

Avoid the anxiety and Pain Paradox Managing anxiety can be done safely and effectively in your practice Avoid ASA III and IV patients Use great care in treating children and the elderly

Know your patients and the drugs you prescribe them

AntibioticsGeneral Considerations


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Antibiotics exploit the differences between prokaryotes (bacteria) and eukaryotes (human cells)Selective toxicity

Cell walls Ribosomal structures Unique enzymes

The more selective a drug the wider the therapeutic index

Empiric vs. Organism specific therapy

Generally antibiotics are either bacteriocidal or bacteriostatic Remember the importance of the patients immune and inflammatory defense mechanisms in

combating infection. Antibiotics do not replace prompt surgical or endodontic managementIndications for Antibiotic Therapy Management of head and neck odontogenic infections Prophylaxis for the prevention of SBE or other medical indications Infection prevention?

Compromised host Long procedure or procedure with high infection rate Little or no evidence for routine use

What are the goals of antibiotic therapy?

To prevent or treat odontogenic infections Choice of antibiotic is typically empiric, a best guess of the typical bacteria known to cause

odontogenic infections Odontogenic infection change with time

Gram + Gram-AAeerroobbiicc AAnnaaeerroobbiicc

What Bacteria?

Choosing antibiotics Consider what bacteria your covering

Early mild odontogenic infection Mixed with Predominantly aerobic Alpha-hemolytic gm + strep

Gram + Gram

Cocc

Rods

StaphStrep*Peptostreptococcus*Peptococcus

*Nisseria*Veillonella

*Lactobacillus*Actino*Eubacteria

*Clostridium

EiknellaH. InfluenzaEnterobacteria*Fusobacterium*Bacteroides

*Anaerobe


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Mild to moderate odontogenic infection Mixed aerobic gm + cocci and anaerobic gm - rods

Severe multi-space occupying odontogenic infection Mixed with Predominantly anaerobic gm- rods

Consider patient medical situation Consider expense

Sinus coverage considerations Sinus flora differs from oral flora Hemophilus Influenza Streptococcus pneumonia, viridans strep Staph aureus

Consider sinus coverage if sinus exposure and infectionPenicillins

Mechanism inhibit crosslinking of cell wall components bacteriocidal (gram + cocci)

Penicillin V

Advantages Bacteriocidal

Pen V is appropriate spectrum for the majority of simple odontogenic infections Clearly the drug of choice for most dental applications generally cheap, well tolerated

Disadvantages resistance, hypersensitivity, rare neurotoxicity

Amoxicillin (Ampicillin) first line drug in treating infections involving the maxillary sinus

Augmentin Amoxicillin and clavulinic acid Broad spectrum- reserved for serious odontogenic infections (all anaerobes, all Strep., methicillin-

sensitive S. aureus, S. epidermidis, H. influenza and Enterococcus)

The AHA protocol for SBE prevention Written by cardiologists for surgeries involving the upper respiratory tract and oral cavity

Intention is to cover common bacterial found in both oral and sinus sites Therefore, Amoxicillin is the drug of choice

o Do not translate that to mean that Amoxicillin is the drug of choice for all odontogenicinfections

Cephalosporins Similar mechanism of action to penicillins 10% cross reactivity with true penicillin allergic patients Susceptible to beta lactamases

Penicillin

PCN-sensitivestreptococci

Penicillinase

PCN-streptococci

Clavulinic acid


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In general:FFiirrssttGGeenneerraattiioonn SSeeccoonnddGGeenneerraattiioonn TThhiirrddGGeenneerraattiioonn

Gram + Gram-/+ Gram-Cefadroxil (Duricef) Cefaclor (Ceclor) Cefixime (Suprax)Cefazolin (Ancef) Cefotetan (Cefotan) Ceftriaxone (Rocephin)Cephalexin (Keflex) Cefuroxime (Ceftin)

Cephalexin (Keflex) Tolerated well orally Inexpensive Similar coverage to Pen V with addition of Staph coverage Good alternative in patients with questionable pen allergyCefuroxime (Ceftin)

Mechanism inhibit crosslinking of cell wall components bacteriocidal (gram + cocci, some gram -)

Advantages Broader coverage (B. fragilis) Sinus coverage in PCN allergic

Staph coverage Disadvantages

10% crossreactivity with PCN allergic

Macrolides Mechanism of action

prevent translocation of polypeptide chain by binding the 50s ribosomal subunit Bacteriostatic Effective in bacteria lacking cell walls (mycoplasma, legionella, chlamydia) Effective against gram + aerobes and some gram- aerobes

Erythromycin (E-mycin)

Coverage bacteriostatic (bacteria lacking cell walls, gram + aerobes, except H. Influenza)

Advantages Used for PCN allergic

Disadvantages bacteriostatic, GI upset Hunt et al.*- Erythromycin was ineffective against 50% of Strep and Staph isolates from

odontogenic infectionsAzithromycin (Zithromax) Similar coverage to erythromycin but fewer resistant strains (better gm - coverage, H. flu) Well tolerated orally, less GI side effects Q 24 hour dosing, high compliance Expensive Equipotent in periapical abscess to Amox- clavulinic acid (J Int Med Res 26:275)Clarithromycin (Biaxin)

Similar to azithromycin in spectrum of coverage Can have similar GI upset to erythromycin BID dosing

Clindamycin (Cleocin)

Mechanism of Action Binds to 50s ribosome and prevents chain elongation bacteriostatic (gram+s, most anaerobes)


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Advantages Similar action to erythromycin, but broader coverage appropriate for odontogenic infections Excellent bone penetration

Disadvantage Pseudomembranous Colitis

Metronidazole (Flagyl)

Mechanism inhibit DNA synthesis bacteriocidal against anaerobe

Advantages Adjunct to penicillin V for anaerobe coverage C. diff colitis treatment

Disadvantages reaction with alcohol nausea, urine changes

Flouroquinolones Mechanism of action

o Inhibit DNA gyraseo

Bactericidal Levofloxacin (Levaquin)

o Third generation flouroquinoloneo Good bone penetration (?)o Relatively broad coverage (comparable to Augmentin)o Tendon rupture issueso QD dosingo Expensive

Antibiotic Costs

Antibiotic Frequency Cost/day

Penicillin V 500 mg QID $0.70

Cephalexin 500 mg QID $1.21

Amoxicillin 500 mg TID $1.23

Clarithromycin 500 mg BID $6.98

CClliinnddaammyycciinn330000mmgg QQIIDD $$77..9955

Amoxicillin-clav, TID $10.39

Azithromycin z-pak QD $11.98

Antibiotic Strategies Acute, mild odontogenic infection (PA abscess or local early single space)

Pen V 500 mg QID with 1gm loading dose Keflex 500 mg QID with 1 gm loading dose for questionable Pen allergic patient Azithromax, Z pack, 500 mg first day, with 250 mg each day for 5 days

Mild to Moderate Odontogenic Infections Pen V 500 mg QID with 1 gm load and Metranidazole 500 mg TID Clindamycin 300 mg QID with 450 mg load for pen allergic Amoxicillin-clavulonate 500 mg TID with 1 gm load

Severe Odontogenic Infections with multi space involvement


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Patient require IV antibiotics!! Ampicillin and sulbactam, 3gm load with 1.5 gm Q6h Clindamycin, 600 mg Q 8h for pen allergic

How long?

No hard and fast rules

Generally 5 days after removal of the source Removal of the source, drainage, adequate dose and frequency of antibiotic are keys to good

outcomes Avoid complications by not using long-term broad coverage

REMEMBER Antibiotics do not replace sound surgical or endodontic treatment of infection source!! Prompt removal of source of infection and incision and drainage of swellings associated with infections

is more important than antibiotic choice and dosing!! When you choose to use antibiotics, use adequate dose and frequency Close follow-up is absolutely neccessary

Antibiotics: Whats new?

Antibiotic resistance Oxacillin resistant Staph Aureus (ORSA) Vancomycin resistant enteroccocus (VRE)

Methicillin Resistant Staph aureus (MRSA)

When to refer Refractory infections Worsening symptoms Airway compromise Multispace involvement Crepitus

Severe trismus Dysphagia

Final thoughts

Have good drug references in your officeo Pocket Pharmacopoeia

Cheap, small, very useful resource ISBN 1-882742-06-0

o Pharmacology and Therapeutics for Dentistry Dental student text with recent edition Fairly good reference

ISBN 0-8016-7962o Mosbys Dental Drug Reference ISBN 0-8016-7851 Final Thoughts

o Lexi Comp Onlineo JADA articles on drug interactions

Series of articles appeared in volume 130 No. 1-6o Goodman and Gilmans The Pharmacological Basis of Therapeutics

The pharmacologists bible Very complete, very detailed, very thick!


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o Use the interneto PubMed is a free database for finding current information in the literature

Expand your armamentarium

The right drug for the right situationKnow the drugs you use

Dont marry a technique or drugEstablish strategies for dealing with anesthetic, analgesic or antibiotic failuresRemember: all drug responses are a bell shaped curve, responses can be different for differentpatients

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