ANTIBIOTICS

ByDr. V.R. Geethika PG 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 multiplication of microorganisms. the growth /

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) Ehrilichs 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

CLASSIFICATION
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

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

B) CHEMICAL STRUCTURE 1. Sulfonamides and related drugs Sulfadiazine and others Sulfones Dapsone (DDS), Paraaminosalicylic acid (PAS). Trimethoprim Pyrimethamine

2. Diaminopyrimidines

3. Quinolones
Nalidixic acid Norfloxacin Ciprofloxacin etc

4. Tetracycline's Oxytetracycline

Doxycycline etc
Chloramphenicol

5. Nitrobenzene derivative

6. -lactam antibiotics
Penicillins Cephalosporins Monobactams Carbapenems

7. Aminoglycosides

Streptomycin
Gentamicin Neomycin etc Erythromycin Roxithromycin

8. Macrolide antibiotics

Azithromycin etc
Polymyxin-B Colistin Bacitracin

9. Polypeptide antibiotics

10. Glycopeptides Vancomycin Teicoplanin

11. Oxazolidinone Linezolid

12. Nitrofuran derivatives

Nitrofurantoin Furazolidone

13. Nitroimidozoles
Metronidozole Tinidazole

14. Nicotinic acid derivatives Isoniazid Pyrazinamide Ethionamide Nystatin Amphotericin-B Hamycin

15. Polyene antibiotics

16. Azole derivatives

Miconazole
Clotrimazole Ketoconazole

17. Others Rifampin

Lincomycin
Clindamycin Spectinomycin

Sod. fusidate
Cycloserine Viomycin Griseofulvin

C) TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE 1. Antibacterial Penicillins Aminoglycosides Erythromycin etc Griseofulvin Amphotericin B Ketoconazole Idoxuridine Acyclovir

2. Antifungal

3. Antiviral

Zidovudine etc

4. Antiprotozoal
Chloroquine Pyrimethamine

Metronidazole
Diloxanide etc

5. Anthelmintic Mebendazole Pyrantel

Niclosamide
Diethyl carbamazine etc

D) SPECTRUM OF ACTIVITY

1. Narrow spectrum

Penicillin G
Streptomycin

Erythromycin

2. Broad spectrum

Tetracyclines
Chloramphenicol

E) Type of action 1. Primarily bacteriostatic Sulfonamides Tetracyclines Chloramphenicol Erythromycin 2. Primarily bactericidal Penicillins Aminoglycosides Rifampin Cotrimoxazole Cephalosporins Vancomycin

Ethambutol

Nalidixic acid
Ciprofloxacin

F) ANTIBIOTICS ARE OBTAINED FROM

1. Fungi Penicillin 3. Actinomycetes Aminoglycosides Tetracyclines Chloramphenicol Macrolides

Cephalosporin
Griseofulvin

2. Bacteria

Polymyxin B
Colistin Bacitracin Tyrothricin

Polyenes

- LACTAM ANTIBIOTICS
Penicillins Cephalosporins

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

CHEMICAL STRUCTURE:

Have - lactam ring

consists of: fused thiazolidine and lactam ring Side chains are attached through amide linkage
Nucleus

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

1. 2. 3.

SEMISYNTHETIC PENICILLINS Acid resistant: alternative to penicillin G:

Phenoxymethyl penicillin (penicillin V)

Methicillin, Oxacillin, Cloxacillin

Penicillinase resistant penicillins:

Extended spectrum antibiotics: Amino penicillins: Ampicillin, Bacampicillin, Amoxicillin Carboxypenicillins: Carbencillin, Ticarcillin 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

ACID RESISTANT

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

PENICILLINASE RESISTANT PENICILLINS

Side chains: protect -lactam ring from attack by staph. Penicillinase Non-penicillinase producing bact are less sensitive Indication:

Penicillinase producing staph.

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:

AMPICILLIN:

Amino penicillins

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

- lactamase enz: produced by many gm +ve and gmve bacteria inactivate -lactam antibiotics by opening -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 -lactamase producing strains Dose: AUGMENTIN: amoxicillin 250mg + clavulanic acid 125mg tab TDS 6 hrly

SULBACTAM

Semisynnthetic - lactamase inhibitor Less potent than clavulanic acidCombined 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 useRheumatic 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 -lactam ring fused to dihydrothiazine ring MOA similar to penicillin but bind to different proteins

parenteral First generation Cephalothin cefazolin Cefuroxime cefoxitin Cefotaxime Ceftizoxime Cef triaxone Ceftazidime cefoperazone Cefepime cefpirome ceftobiprole

oral Cephalexin Cephradine cefadroxil Cefaclor Cefuroxime axetil Cefixime Cefpodoxime proxetil Cefdiuir ceftibuten

Second generation Third generation

Fourth generation Fifth generation

CEPHALOSPORIN III AND IV HIGHLY ACIVE: GM-VE (AEROBES) LESS ACTIVE: GM +VE CEPHALOSPORIN II HIGHLY ACIVE: GM-VE ANAEROBES CEPHALOSPORIN I HIGHLY ACIVE: GM+VE LESS ACTIVE: GM -VE

PENICILLIN GM +VE

FIRST GENERATION
Developed in 1960s Spectrum of activity:

High activity against Gm +ve but weaker against Gm ve bacteria. Active against most PnG sensitive org. Highly resistant to Staph. -lactamase

Cephalothin 1st cephalosporin Cefazolin

i.m very painful, used only i.v. 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 -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 -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 1990s Antibacterial spectrum similar to third generation Highly resistant to -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 Oxytetracycline Group III

Doxycycline Minocycline

Demeclocyline Methacycline

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

Tetracycline oxytetracycline source Potency Intestinal absorption Oxy T: S. rimosus T: semisynthetic Low Moderate

demeclocycline Deme: S. aureaofaciens Intermediatae Moderate

Doxycycline Minocycline semisynthetic High Complete

Plasma protien binding

Elimination Plasma t1/2 Dosage Alteration of intestinal flora Incidence of diarrhoea Phototoxicity

Oxy T: Low T: intermediate

Rapid renal excretion 6-10hr 250-500mg QID/ TDS Marked High Low

High
Partial metabolism Slow 16-18hr 300mg BD Moderate Intermediate Highest

High
Doxy: in faeces Mino: urine & bile 18-24hr 200mg initially; then 100-200mg OD Least Low high

Specific toxixity

Tooth discoloration

Diabetes insipidus

Low renal 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 used in renal and hepatic insufficiency

pregnancy
Cautiously Do

not mix injectable tetracyclines with penicillin: beyond expiray date should never be

inactivation occurs
Preperation

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 sulfadoxinepyrimethamine, 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 AMAs. 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

PharmacokineticsHighly 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 infections Classification *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

Norfloxacin Ofloxcain Ciprofloxacin

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 gatifloxaci Moxifloxacin

more active against gm+ve & anerobes 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, satranidazole MOA Interferes with DNA function Pharmacokinetics 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

DRUG INTERACTIONS

respiratory depression with neuro muscular blockers

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 malformations High 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
Standard general prophylaxis Unable to take oral medication

ANTIMICROBIAL AGENT
amoxicillin

REGIMEN
A: 2 gm C: 50 mg/kg Orally 1 hr preoperatively A: 2 gm C: 50 mg/kg IM/IV 30 min preoperatively

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

Allergic to penicillin

Azithromycin, clarithromycin

A: 500 mg C: 15 mg/kg 1 hr preoperatively

A; 2 gm C; 50 mg/kg 1 hr preoperatively A: 600mg C: 20 mg/kg IV 30 min preoperatively A: 1 gm C:25 mg/kg IM/IV 30 min preoperatively

Allergic to penicillin & unable to take oral medication

Cephalexin, cefadroxil

clindamycin

cephazolin

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 Gilmans The pharmacological basis of Therapeutics, 8th edition Antibiotic selection in head and neck infectionsOral Maxillofacial Surg Clin N Am 15 (2003) 1738 Antibiotic therapymanaging odontogenic infectionsDent Clin N Am 46 (2002) 623633

Thank you

CONTENTS IN NEXT SESSION

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