ANTIBIOTICS

By- Dr. V.R. GeethikaPG student

CONTENTS

Introduction History Classification B- lactams Tetracylines Chloramphenicol Aminoglycoslides Macrolides

Sulfanamides Fluoroquinolones Metranidazole Clindamycin Vancomycin Prophylaxis of

bacterial endocarditis

INTRODUCTION

Drug: any substance / product that is used /

is intended to be used to modify / explore physiological systems / pathological states for the benefit of one recipient.

Chemotherapy : it is the treatment of

systemic infection with specific drugs that selectively suppress the infecting microrganism without significantly affecting the host.

Antibiotic agent

(Greek- anti means against and biosis means life).

Chemical substances produced by microorganisms, which selectively suppress the growth of or kill other microrganism at very low concentrations.

Antimicrobial agent :

Substances that will suppress the growth / multiplication of microorganisms.

• It designates synthetic as well as naturally obtained drugs.

• May be antibacterial, antiviral / antifungal.

Antibacterial agent : substances that destroy or suppress the

growth / multiplication of bacteria. They are classified as antibiotic or synthetic agents.

Pharmacodynamics : what the drug does to the body.

Pharmacokinetics : what the body does to the drug.

HISTORY

1) Period of empirical use – 17th century

2) Ehrilich’s phase of dyes and organometallic

compounds (1890 – 1935)

3) Modren era – Domagk in 1935.

1877 – Pasteur - phenomenon of antibiosis

1929 - Fleming – named Pencillin

(unpurified)

1939 – Chain & Florey – clinical use.

1940s – Waksman & his collegues –

discovered streptomycin

A)Mechanism of action :

1. Inhibit cell wall synthesis

• Penicillins

• Cephalosporins

• Vancomycin

• Bacitracin

2. Cause leakage from cell membranes

• Polypeptides – Polymycins, colistin, Bacitracin

• Polyenes – Amphotericin B, Nystatin

CLASSIFICATION

3. Inhibit protien synthesis• Tetracycline• Chloramphenicol• Erythromycin• Clindamycin• Linezolid

4. Cause misleading of m- RNA code and effect permeabilty

• Aminoglcosides – streptomycin, gentamycin

5. Inhibit DNA gyrase

• Fluoroquinolones – Ciprofloxacin

6. Interfere with DNA function

• Rifampacin

• Metronidozole

7. Interfere with DNA synthesis

• Idoxuridine

• Acyclovir

• Zidovudine

8) Interfere with intermediary metabolism

Sulfonamides

Sulfones

Ethambutol

1. Sulfonamides and related drugs

• Sulfadiazine and others

• Sulfones – Dapsone (DDS), Paraaminosalicylic acid

(PAS).

2. Diaminopyrimidines

• Trimethoprim

• Pyrimethamine

3. Quinolones

• Nalidixic acid Ciprofloxacin etc

• Norfloxacin

B) CHEMICAL STRUCTURE

4. Tetracycline's

• Oxytetracycline

• Doxycycline etc

5. Nitrobenzene derivative

• Chloramphenicol

6. -lactam antibiotics

• Penicillins

• Cephalosporins

• Monobactams

• Carbapenems

7. Aminoglycosides• Streptomycin• Gentamicin• Neomycin etc

8. Macrolide antibiotics• Erythromycin• Roxithromycin• Azithromycin etc

9. Polypeptide antibiotics• Polymyxin-B• Colistin• Bacitracin

10.Glycopeptides

• Vancomycin

• Teicoplanin

11.Oxazolidinone

• Linezolid

12.Nitrofuran derivatives

• Nitrofurantoin

• Furazolidone

13.Nitroimidozoles

• Metronidozole

• Tinidazole

14.Nicotinic acid derivatives• Isoniazid• Pyrazinamide• Ethionamide

15.Polyene antibiotics• Nystatin• Amphotericin-B• Hamycin

16.Azole derivatives • Miconazole• Clotrimazole• Ketoconazole

17.Others

• Rifampin

• Lincomycin

• Clindamycin

• Spectinomycin

• Sod. fusidate

• Cycloserine

• Viomycin

• Griseofulvin

1. Antibacterial • Penicillins• Aminoglycosides• Erythromycin etc

2. Antifungal • Griseofulvin• Amphotericin B• Ketoconazole

3. Antiviral• Idoxuridine• Acyclovir• Zidovudine etc

C) TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE

4. Antiprotozoal

• Chloroquine

• Pyrimethamine

• Metronidazole

• Diloxanide etc

5. Anthelmintic

• Mebendazole

• Pyrantel

• Niclosamide

• Diethyl carbamazine etc

1. Narrow spectrum

• Penicillin G

• Streptomycin

• Erythromycin

2. Broad spectrum

• Tetracyclines

• Chloramphenicol

D) SPECTRUM OF ACTIVITY

E) Type of action

1. Primarily bacteriostatic

• Sulfonamides

• Tetracyclines

• Chloramphenicol

• Erythromycin

• Ethambutol

2. Primarily bactericidal

• Penicillins

• Aminoglycosides

• Rifampin

• Cotrimoxazole

• Cephalosporins

• Vancomycin

• Nalidixic acid

• Ciprofloxacin

1. Fungi

• Penicillin

• Cephalosporin

• Griseofulvin

2. Bacteria

• Polymyxin B

• Colistin

• Bacitracin

• Tyrothricin

3. Actinomycetes

• Aminoglycosides

• Tetracyclines

• Chloramphenicol

• Macrolides

• Polyenes

F) ANTIBIOTICS ARE OBTAINED FROM

Β- LACTAM ANTIBIOTICS

Penicillins Cephalosporins

Penicillins – 1st antibiotic in 1941. Least toxic drug. Obtained from penicillium notatum.

CHEMICAL STRUCTURE:

Have ß- lactam ring

Nucleus consists of: fused thiazolidine and ß-lactam ring

Side chains are attached through amide linkage

MECHANIASM OF ACTION

Interfere with synthesis of cell wall Interfere with peptidoglycans by

inhibiting transpeptidases Presence of penicillin binding proteins

(PBP)

Gm -ve Gm +ve

CLASSIFICATION

NATURAL PENICILLIN: Penicillin G Procaine penicillin Benzathine penicillin G SEMISYNTHETIC PENICILLINS Acid resistant: alternative to penicillin G:

Phenoxymethyl penicillin (penicillin V) Penicillinase resistant penicillins:

Methicillin, Oxacillin, Cloxacillin Extended spectrum antibiotics:1. Amino penicillins: Ampicillin, Bacampicillin, Amoxicillin2. Carboxypenicillins: Carbencillin, Ticarcillin3. Ureidopenicillins: Piperacillin, Mezlocillin

Beta-lactamase inhibitors: Clavulanic acid, Sulbactam

SEMISYNTHETIC PENICILLINS

Produced by combining specific side chains

Produced to overcome shortcomings of natural penicillin: Poor oral efficacy Susceptibility to penicillinase Narrow spectrum of activity

Phenoxymethyl penicillin (penicillin V) Similar to penicillin G except that it is acid stable Used in dental infections, trench mouth, strep, &

pnemococcal infections. t1/2 – 30 – 60min. Dose: 250-500mg; infants: 60mg; children: 125-

250mg – 6 hrly

Side chains: protect ß-lactam ring from attack by staph. Penicillinase

Non-penicillinase producing bact are less sensitive

Indication: Penicillinase producing staph.

PENICILLINASE RESISTANT PENICILLINS

ACID RESISTANT

Methicillin: penicillinase resistant but not acid resistant

Adr: haematuria Albuminuria Reversible intestinal nephritis

Cloxacillin: penicillinase as well as acid resistant isoxazolyl side chain

More active.Incompletely absorbed if taken empty

stomach.

t1/2 about 1 hr

Dose: 0.25-0.5g cap orally 6hrly 0.25 – 1g inj. i.v / i.m

Methicillin resistant Staph. aureus – insensitive to all penicillinase resistant Pns as well as to erythromycin, aminoglycoslides, tetracyclins.

DOC – vancomycin, linezolid, ciprofloxacin.

EXTENDED SPECTRUM ANTIBIOTICS:

Amino penicillins AMPICILLIN:

Active against gram +ve & gram -ve - None is resistant to β-lactamases

Oral absorption incomplete but adequate Food interferes absorption t1/2 – 1hr Dose: 0.5 – 2g oral/i.v/i.m – 6hrly Children – 25-50mg/kg/day

ADR - diarrohea

AMOXICILLIN: Similar to ampicillin in all aspects except:

Oral absorption better Food does not interfere absorption Incidence of diarrhoea less Higher and more sustained release of blood

levels Most commonly used in dental treatments.

Dose: 0.25-1gm TDS oral

CARBOXYPENICILLINS

CARBENCILLIN: Activity against Pseudomonas and Proteus

(not inhibited by PnG and aminoPn)

Gm+ve cocci and Klebsiella not inhibited

Neither penicillinase resistant nor acid

resistant

Inactive orally

T1/2 – 1hr

Dose: used as Na salt 1-2gm i.m or 1-5gm i.v

BETA-LACTAMASE INHIBITORS

ß- lactamase enz: produced by many gm +ve and gm-ve bacteria – inactivate ß-lactam antibiotics by opening ß-lactam ring.

Eg; penicillinase

Inhibitors of this enz. are: Clavulanic acid Sulbactam Tazobactam

CLAVULANIC ACID

Obtained from Streptomyces clavuligerus Progressive inhibitor – Rapid oral absorption/can be injected t1/2 – 1hr Uses:

Establishes activity of amox. against ß-lactamase producing strains

Dose: AUGMENTIN: amoxicillin 250mg +

clavulanic acid 125mg tab TDS 6 hrly

SULBACTAM

Semisynnthetic ß- lactamase inhibitor

Less potent than clavulanic acid-

Combined with Ampicillin

Oral absorption inconsistent- given parenterally

Dose:

SULBACIN: ampicillin 1g + sulbactam

0.5g/vial inj: deep IM/IV inj 6-8 hrly (1-2vials)

USES

PnG is DOC – Sequelae of dental caries Peridontal abscess Periapical abscess Acute suppurative pulpitis NUG Oral cellulitis. Medical uses – strep. Infections – pharyngitis,

tonsilitis, otitis media, scarlet fever, rheumatic fever, pnemococcal & meningococcal infections, gonorrhoea, syphilis – benzathine penicillin.

Prpphylactic use- Rheumatic fever – benzathine penicillin 1.2MU

every 4wks upto 18yrs. Surgical prophylaxis – procaine penicillin 1MU,

1hr before surgery Gonorrhoea / syphillis – procaine Pn/

benzathaine Pn 2.4MU Bacterial endocarditis Agranulocytosis pts

ADVERSE EFFECTS Local irritancy and direct toxicity:

Pain at inj. site, nausea on oral ingestion, thrombophlebitis of injected vein

CNS symptoms Intethecal inj- not recommended – causes arachnoiditis

& degenerative changes. Hypersensitivity: more common after parenteral

administration Rash, itching, urticaria, fever, wheezing, angioneurotic edema etc Individual who tolerated Pn earlier may show allergy on

subsequent admnistration and vice vrsea. Scratch test (2-10U) injected intradermally. Benzyl – penicilloyl – polylysine is safer

Diarrhoea Superinfection: rare Jerish-Herxheimer reaction: seen in syphilitic patients

DRUG INTERACTIONS

Concurrent therapy of penicillin & aminoglycosides are not advised because the former may inactivate the later

Probenecid - retards the renal excretion. Hydrocortisone inactivates Pn if mixed in i.v

sol. Given with oral contraceptives, it fails to act.

CEPHALOSPORINS

Semisynthetic antibiotics – obtained from fungus cephalosporium

Chemically related to penicillin Nucleus consists of ß-lactam ring fused

to dihydrothiazine ring MOA similar to penicillin – but bind to

different proteins

parenteral oral

First generation Cephalothincefazolin

CephalexinCephradinecefadroxil

Second generation Cefuroximecefoxitin

CefaclorCefuroxime axetil

Third generation CefotaximeCeftizoximeCef triaxoneCeftazidimecefoperazone

CefiximeCefpodoxime proxetilCefdiuirceftibuten

Fourth generation Cefepimecefpirome

Fifth generation ceftobiprole

CEPHALOSPORIN – IHIGHLY ACIVE: GM+VELESS ACTIVE: GM -VE

PENICILLINGM +VE

CEPHALOSPORIN – IIHIGHLY ACIVE: GM-VEANAEROBES

CEPHALOSPORIN – III AND IVHIGHLY ACIVE: GM-VE (AEROBES)LESS ACTIVE: GM +VE

FIRST GENERATION Developed in 1960’s Spectrum of activity:

High activity against Gm +ve but weaker against Gm -ve bacteria.

Active against most PnG sensitive org. Highly resistant to Staph. ß-lactamase

Cephalothin – 1st cephalosporin i.m – very painful, used only i.v.

Cefazolin – parentral, used in surgical prophylaxis t1/2 – 2hrs. Dose – 0.25g 8hrly, 1hr 6hrly.

Cefalexin – commonly used Dose:– 0.25 – 1g; 6-8hrly Children: 25 – 100mg/kg/day

Cefadroxil - congener of cephalexin. Good tissue penentration

t1/2 – 12hrs Dose- 0.5 – 1g BD

SECOND GENERATION

More active against Gm –ve org. & anaerobes Retain significant activity on Gm +ve cocci Highly resistant to ß-lactamase produced by Gm –ve

org

Cefoxitin – Used in tt of anaerobic and mixed surgical infection. Dose 1-2g i.m/i.v; 6-8hrly

Cefuroxime – tolerated by i.m Have higher CSF levels Dose – 0.75 – 1.5g i.m/i.v; 8hrly. Children – 30-100mg/kg/day.

Cefuroxime axetil – Ester of cefuroxime. Effective orally Used in dental infections. Dose – 125,250,500mg cap

Cefaclor – More a.ctive. Dose – 250mg cap 125mg/5ml dry syr

THIRD GENERATION

Highly augmented activity – Aerobic Gm –ve enterobacteriaceae

Not active on anaerobes Less active against – Gm +ve cocci Highly resistant to ß-lactamase produced by Gm –ve org

Cefotaxime - Prototype Used in life threatening resistant/ hospital – aquired

infections, septicaemias, immunocomprimised patients.

t1/2 – 1hr Dose- 1-2g i.m/i.v 6-12hrly Children 50-100mg/kg/day

Cefixime – Orally active used in respiratory, urinary and

biliary infections. t1/2 – 3hrs Dose – 200 – 400mg BD

FOURTH GENERATION

Developed in 1990’s Antibacterial spectrum similar to third generation Highly resistant to ß-lactamase Only parenteral route

Cefipime – High potency and extended spectrum so effective in

hospital – acquired pneumonia, febrile neutropenia, bacteraemia, septicaemia

Dose 1-2gi.v; 8-12hrly

Cefiprome – zwitterion character permits penentration through porin channels in gram –ve org

FIFTH GENERATION

Newly developed. Ceftobiprole – effective against MRSA &

pseudomonas.

ADVERSE EFFECTS

Well tolerated than penicillins but more toxic Pain: IM route; thrombophlebitis: IV route Diarrhoea Hypersensitivity reactions: rashes common Bleeding occurs with cephalosporins

(cefaperazone; ceftriaxone) Neutropenia Thrombocytopenia Disulfiram like reaction with alcohol.

GUIDING PRINCIPLE FOR THE USE OF CEPHALOSPORINS :

Cephalosporins are expensive and should not be used where an equally effective, alternative antibiotic is available.

None of them is agent of choice of anaerobic infections.

Except for cefotaxime, ceftriazone, the CNS penetration of cephalosporins is poor.

DRUG INTERACTONS

probenecid decreases renal clearance of cefuroxime

Nephrotoxicity with aminoglycosides and furosemide

CARBEPENEMS

Imipenem - Very broad spectrum includes – gram +ve, enterobacteriaceae, anaerobes.

Impenem – rapid hydrolysis by enzyme dehydropepetidase I – wall of renal tubular cells.

Given along with cilastatin – reversible inhibitor of dehydropepetidase I

Dose – 0.5i.v; 6hrly

TETRACYCLINES Broad spectrum antibiotic Obtained from soil actinomyces 1st – chlortetracycline - 1948 Bacteriostatic Active orally MOA:

Inhibit protein synthesis bind to 30s ribosome and inhibit aminoacyl

tRNA attachment to ‘A’ site.

Antimicrobial spectrum:

All gm +ve and –ve Cocci

Gm +ve/ -ve bacilli

Spirochetes are quite sensitive

On the basis of chronology of development, convenience of description, divided into 3 groups.

Group I Group II

Tetracycline Demeclocyline Oxytetracycline Methacycline

Group III

Doxycycline Minocycline

Absorption better in empty stomach

Chelating property: form insoluble complexes

with calcium and other metals

Milk, iron, antacids, sucralfate reduce their

absorption.

Secreted in milk in sufficient amounts to affect

suckling infant

Group I Tetracyclineoxytetracycline

Group IIdemeclocycline

Group IIIDoxycyclineMinocycline

source Oxy T: S. rimosusT: semisynthetic

Deme: S. aureaofaciens

semisynthetic

Potency Low Intermediatae High

Intestinal absorption

Moderate Moderate Complete

Plasma protien binding

Oxy T: LowT: intermediate

High High

Elimination Rapid renal excretion

Partial metabolismSlow

Doxy: in faecesMino: urine & bile

Plasma t1/2 6-10hr 16-18hr 18-24hr

Dosage 250-500mg QID/ TDS

300mg BD 200mg initially; then 100-200mg OD

Alteration of intestinal flora

Marked Moderate Least

Incidence of diarrhoea

High Intermediate Low

Phototoxicity Low Highest high

Specific toxixity Tooth discoloration

Diabetes insipidus Low renal toxicity, vestibular toxicity,

ADVERSE REACTIONS

Liver damage Kidney damage – fancony syndrome phototoxicity Teeth and bones Diabetes insipidus Vestibular toxicity Superinfection Hypersensitivity

EFFECT OF TETRACYCLINE ON TEETH

Due to chelating property, calicium-tetracycline chelate gets deposited in developing teeth Travels in blood to coronal portion of pulp Extends through subodontoblatic layer to

predentin Bonds chemically to Ca-ions Diffuses: site of dentin formation Stable: orthophosphate complex

Discoloration may occur if given during pregnancy or postpartum to child

Critical periods: In deciduous dentition: (first mm of dentin

near DEJ) – 4month IU to 3 months post-partum (max/ mand

incisors) 5 months IU to 9 months post partum (canines)

Permanent max/ mand incisors and canines: 3-5 months post partum to 7 yrs

Oxycycline, Doxycycline – less chances of discoloration

C/F: Yellowish or brown discoloration Becomes more brownish over a period of time Fluoresce under UV light Dentin more heavily stained than enamel

PRECAUTIONS:

Not be used in children, lactating mothers and

pregnancy

Cautiously used in renal and hepatic

insufficiency

Do not mix injectable tetracyclines with

penicillin: inactivation occurs

Preperation beyond expiray date should never

be used.

USES

Acute dental infections Refractory periodontal disease – 1g/day;

2weeks Medical uses – mixed infections, venereal

diseases, atypical pneumonia, cholera, brucellosis, plague, rickettsial infections.

Others- UTI, amoebiasis. Adjuvant to sulfadoxine-pyrimethamine, acne, copd

Pharmacokinetics: Completely absorbed after oral ingestion Penetrates blood brain barrier Crosses placenta and is secreted in bile and milk. Conjugated in liver Neonates and cirrhotic who have low conjugating

ability, lower doses. t1/2 – 3-5hrs

Doses: 250-500mg; 6hrly Children: 25-50mg/kg/day Chloramphenicol palmitate – insoluble tasteless

ester. Chloramphenicol succinate – soluble but inactive

ester.

PRECAUTIONS

Never use for minor infections or of undefined etiology

Do not use if it is treatable by other AMA’s. Avoid repeated doses Daily dose < 2-3g; duration 2-3weeks. Max dose < 28g

USES

Enteric fever. H. influenzae meningitis Anaerobic infections Intraocular infections Topically in conjuctivitis, ear infections

AMINOGLYCOSIDES

Obtained from soil actinomycetes. Streptomycin – 1st discovered – 1944 – by

Waksman MOA – Causes misleading of m-RNA code Binds to 30s & 50s subunits – interfere with the

polysome formation and causes misleading of m-RNA Streptomycin, Gentamycin, Kanamycin, Amikacin, Neomycin, Framycetin

STREPTOMYCIN • Oldest

• Obtained from Streptomyces griseus

• It is a bactericidal agent and effective against mycobacterium.

• Active against aerobic gram -ve, at high conc. gram +ve

Pharmacokinetics- Highly ionized Higher conc in CSF Not metabolized – excreted unchanged in urine T1/2 – 2-4hrs

Adverse effects :

Vestibular disturbances.

lowest nephrotoxicity.

Hypersensitivity reactions are rare

Super infections are not significant.

Paresthesias are occasional.

Topical use is contraindicated

Dosage : .

Acute infections : 1g I.m. BD for 7-10 days for adults.

40mg/kg/day divided into two doses IM

USES

Tuberculosis SABE Plague Tularaemia Brucellosis

GENTAMICIN

Obtained from – Micromonospora purpurea – 1964

Acitve against gram –ve. Relatively more nephrotoxic. Used in acute infections Dose – 3-5mg/kg/day, i.m.; 8hrly

MACROLIDES

Drugs in this category: Erythromycin

Newer macrolides: Roxithromycin Clarithromycin Azithromycin

ERYTHROMYCIN

Obtained from – streptomyces erytherus – 1952 Alternative to Pn. MOA:

Acts by inhibiting bacterial protein synthesis Combines with 50S ribosome and hinder

translocation of elongated peptidde chain back from ‘A’ site to ‘P’ site.

Bacteriostatic Cidal at high concentration More active in alkaline pH

Antibacterial spectrum: Narrow spectrum Mostly gm +ve and few gm –ve (similar to

penicillin)

Pharmacokinetics: Acid labile Acid stable esters are better absorbed To protect for gastric secretion – enteric

coated tablets Food delays absorption t1/2 - 1.5hr

Dose: Children: 30-60mg/kg/day orally in 4 divided

doses Adults: 250-500mg 6 hrly Max. dose - 4g/day

ADR: Mild to severe epigastric pain Reversible hearing impairment Hypersensitivity reac: rashes, fever Hepatitis/ cholestatic jaundice

USES

Second DOC to penicillin. Periodontal/ periapical infections NUG Postextraction instructions Gingival cellulitis Medical uses- pharyngitis, tosilitis, ENT

infections

DRUG INTERACTIONS

Inhibit hepatic oxidation of many drugs May antagonise therapeutic effects of

lincomycin & clindamycin May potentiate actions of neuromuscular

blockers,oral anticoagulants,theophylline,terfenadine,astemizole, cisapride- toxicity increases(inhibition of CYP3A4) - Ventricular arrythmias & death

To overcome backdrops of erythromycin: Narrow spectrum Gastric intolerance Poor tissue penetration Less half life THE SEMISYNTHETIC MACROLIDES WERE

INTRODUCED

ROXITHOROMYCIN: Antibacterial spectrum similar to erythromycin T1/2: 12 hrs: bd or single dose

CLARITHROMYCIN: Active against prevotella melaninogenica and

bacteroides Dose:

Children: 15mg/kg/day BD Adults: 250-500mg/day12 hrly

DRUG INTERACTIONS

Antacids containing Al & Mg salts reduce rate of absorption

Increase risk of ergot toxicity Increase serum concentrations of digoxin&

cyclosporin

SULFONAMIDES

Effective against pyogenic bacterial infectionsClassification *short acting (4-8 hr): sulfadiazine *intermediate acting (8-12 hr):

sulfamethoxazole, sulfamoxole *long acting (~7days): sulfadoxine,

sulfamethopyrazole *special purpose sulfonamides:

sulfacetamide sod, sulfazalazine, mefenide, silver sulfadiazine

Bacteriostatic Active against gram +ve and gram –ve MOA: inhibit bacterial folate synthetase

USES: Systemic use of sulfonamides alone is rare now UTI Pharyngitis Gum infection Second DOC – lymphogranuloma venerum Cotrimazole - trimethoprim + sulfamethoxale Pyritmethamine + sulfamethoxale - malaria

ADVERSE EFFECTS

DOSE DEPENDENT EFFECTS: Crystalluria, Hypersensitivity and Photosensitivity, steven johnson syndrome and exfoliaative dermatitis.

Haemolysis in pts with G6 PD deficiency

Dose independent: nausea, vomiting, epigastric pain, anorexia, hepatitis

CONTRA INDICATIONS

Hypersensitivity Severe renal and hepatic insufficiency Infants < 4 wks Megaloblastic anaemia Pregnancy lactation

DRUG INTERACTIONS

Inhibit metabolism of phenytoin, tolbutamide and warfarin – enhance their action.

Displace methotrexate from binding decrease renal excretion.

FLOUROQUINOLONES

First generation• Norfloxacin• Ofloxcain• Ciprofloxacin

Second generation• Comefloxacin• Levofloxacin• Gatifloxacin• Moxifloxacin

MOA - Inhibit bacterial DNA gyrase

Ciprofloxacin Active against aerobic gram –ve org,

Enterobacteriaceae & Neisseria. Rapid bactericidal activity Long postantibiotic effect Low frequency of mutational resistance Active against b-lactams & aminoglycosides

resistant bacteria. Less active against acidic pH

Pharmacokinetics- Absorbed orally Food delays absorbtion High tissue penetration

Adverse effects- Safety drug GI CNS Hypersensitivity Tendonitis

USES

Broad spectrum activity Employed for blind therapy of any infections Not a suitable drug for majority of orodental

infections may be used in some mixed infections Medical uses – UTI, typhoid, gonorrhoea, skin and

soft tissue infections

Ofloxacin more active against gatifloxaci gm+ve & anerobes Moxifloxacin used in dentistry

Dose – ciprofoxacin – 250 – 750mg; BD oral 100- 200mg; i.v ofloxacin – 200 – 400mg; BD oral 200mg; i.v levofloxacin – 500mg; OD oral; i.v

DRUG INTERACTIONS

Plasma concentration of theophylline, caffeine & warfarin are increased by ciprofloxacin due to inhibition of metabolism - toxicity may occur

Nsaid`s may enhance the CNS toxicity of FQ`S Antacids sucralfate and iron salts given

concurently reduce absorption.

METRONIDAZOLE Nitroimidazole Broad spectrum antiprotozoal drug Has efficacy in anaerobic bacterial infections Other congeners – tinidazole, ornidazole,

secnidazole, satranidazoleMOA - Interferes with DNA functionPharmacokinetics completely absorbed Adequate concentration in CSF, saliva Metabolised in the liver T1/2 ---8hrs Dose – 200-400mg TDS

USES

Especially indicated in Acute periapical abscess Periodontitis ANUG Pericoronitis & Other oral and salivay gland infections Medical uses –pelvic surgery, appendicectomy,

brain abscess,, endocarditis.

ADVERSE EFFECTS

Anorexia, nausea, metallic taste Glossitis, dryness of mouth, dizziness,

rashes,neutropenia Peripheral neuropathy and seizures. On i.v. – thrombophlebitis.

CONTRA INDICATIONS

Neurological disorders Blood dyscrasias Pregnancy (1st trimester)

DRUG INTERACTIONS

can produce disulfuram like reactions Cimitidine, microsomal enzyme inhibitors –

reduce metabolism. Enhances warfarin action by inhitbiting its

metabolism.

CLINDAMYCIN

Lincosamide anatibiotic MOA- Inhibits protein synthesis by binding with

30s ribosome's activity against gm+ve cocci & anaerobes Exhibits partial cross resistance with

erythromycin

Pharmacokinetics – Oral absorption is good Penetrates into skeletal & soft tissues but not

brain & CSF T1/2 -3hrs Dose – 150 – 300mg QID oral 200- 600mg; i.v.; 8hrly

USES

It is a reserve drug – anaerobic bacteria Because of good penetration into bone , given in

dento alveolar abscess & other bone infections Alternative antibiotic prophylaxis of endocarditis

ADVERSE EFFECTS

Rashes, urticaria, abdominal pain Diarrhoea Pseudomembranous enterocolitis – caused by C.

difficile superinfection – fatal

respiratory depression with neuro muscular blockers

DRUG INTERACTIONS

VANCOMYCIN

Glycopeptide antibiotic Bactericidal to gram +ve , anaerobes,

diptheroids. MOA – inhibiting cell wall synthesis Pharmacokinetics – Not absorbed orally i.v. – penetrates into serous cavities, meninges T1/2 – 6hrs. Dose – 125- 500mg; 6hrly; oral 500mg; 6hrly

USES

Second choice drug to pseudomembranous enterocolitis.

MRSA infections Dialysis patients Undergoing cancer chemotherapy Penicillin allergic pts Prophylaxis of endocarditis

ADVERSE EFFECTS

Nerve deafness Kidney damage Skin allergy Fall in b.p Red man syndrome – rapid i.v inj causes chills,

fever, urticaria, flushing

ANTIBIOTIC PROPHYLAXIS FOR MEDICALLY COMPROMISED PATIENTS

Moderate risk:(1) Acquired valvular dysfunction(2) Hypertrophic cardiomyopathy(3) Mitral valve prolapse with regurgitation and/or thickened(3) valve leaflets(4) congenital cardiac malformationsHigh risk:(1) Prosthetic cardiac valves(2) Previous bacterial endocarditis(3) Complex cyanotic congenital heart disease(4) Surgically constructed systemic pulmonary shunts

Dental procedures:

(1) Periodontal procedures, e.g. surgery, scaling and root planing, probing, and recall maintenance(2) Dental implant placement and reimplantation of avulsed teeth(4) Endodontic instrumentation or surgery only beyond the apex(5) Subgingival placement of antibiotic fibers or strips(6) Initial placement of orthodontic bands but not brackets(7) Intraligamentary local anesthetic injections(8) Dental extraction and surgeries

CIRCUMSTANCE ANTIMICROBIAL AGENT

REGIMEN

Standard general prophylaxis

amoxicillin A: 2 gmC: 50 mg/kgOrally 1 hr preoperatively

Unable to take oral medication

Ampicillin, clindamycin 600mg ; 1hr cefazolin 1g i.m;i.v

A: 2 gmC: 50 mg/kgIM/IV 30 min preoperatively

Allergic to penicillin Azithromycin, clarithromycin

A: 500 mgC: 15 mg/kg1 hr preoperatively

Allergic to penicillin & unable to take oral medication

Cephalexin, cefadroxil A; 2 gmC; 50 mg/kg1 hr preoperatively

clindamycin A: 600mgC: 20 mg/kgIV 30 min preoperatively

cephazolin A: 1 gmC:25 mg/kgIM/IV 30 min preoperatively

REFERENCES

Essentials of Medical Pharmacology, K. D. Tripathi, 5th edition

Pharmacology and Pharmacotherapeutics, R.S. Satoskar, S.D. Bhandarkar, Nirmala Rege, 19th edition

Goodman and Gilman’s The pharmacological basis of Therapeutics, 8th edition

Antibiotic selection in head and neck infectionsOral Maxillofacial Surg Clin N Am 15 (2003) 17–38

Antibiotic therapy—managing odontogenic infectionsDent Clin N Am 46 (2002) 623–633

Thank you

CONTENTS IN NEXT SESSION

Anti tubercular drugs Anti fungal Anti viral Anti helementic Anti protozoal Antibiotics in special conditions conclusion