Antimicrobials general I
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Transcript of Antimicrobials general I
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ANTIMICROBIALS
DR PADMAVATHI S
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ANTIBIOTICS OR ANTIMICROBIALS ???
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HISTORY
• Mouldy curd boils• Chaulmoogra oil leprosy• Mercury syphilis• Cinchona bark fever• Ehrlich’s phase of dye
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• PENICILLIN DISCOVERY
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Classification BASED ON • Chemical structure• Mechanism of action• Type of organism against which primarily active• Spectrum of activity• Type of action• Source
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Chemical StructureSulfonamides – sulfadiazine , dapsoneDiaminopyridines – trimethoprim, pyrimethamineQuinolones – nalidixic acid, ciprofloxacinBeta lactums – penicillins, cephalosporinsNicotinic acid derivative – isoniazid, pyrazinamide, ethionamideAzole derivatives – miconazole, ketoconazoleMacrolides – azithromycin, clarithromycin
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Mechanism of action• Cell wall synthesis inhibitors – penicillin, cephalosporin• Leakage of cell membranes – amphotericin B• Protein synthesis inhibitors – tetracyclines, macrolides• Inhibit DNA gyrase - Fluoroquinolones• Interfere DNA function – rifampicin • Interfere with intermediary metabolism – sulfonamides
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Type of organism against which primarily active• Antibacterial • Antifungal• Antiviral• Antiprotozoal• Anthelmintic
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Spectrum of activity• Narrow spectrum
• Broad spectrum
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Type of action•Bacterio static
•Bacterio cidal
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Sources • Fungi – penicillin
• Bacteria – polymyxin B
• Actinomycetes – aminoglycosides
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Problems • Toxicity• Hypersensitivity reactions• DRUG RESISTANCE• Superinfection• Nutritional deficiencies• Masking of an infection
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Drug resistance• Unresponsiveness of a microorganism to an antimicrobial agent• Natural & acquired • Mutation / gene transfer• Stable & heritable genetic change – spontaneously & randomly
– vertical transfer
• Drug tolerant• Drug destroying• Drug impermeable
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CROSS RESISTANCE
• Resistance to one AMA conferring resistance to another AMA• to which the organism has not been exposed• Complete• Partial
• No indiscriminate use• Prefer narrow spectrum drugs• Combination of drugs
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Superinfection/ Suprainfection • Appearance of new infection as a result of antimicrobial therapy
• Broad & extended spectrum antibiotics
• Tetracycline, chloramphenicol
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Predisposing factors• Corticosteroid therapy• Malignancy• AIDS• Agranulocytosis• Diabetes mellitus
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Examples of superinfection• Candida albicans – oral thrush, vulvovaginitis• Resistant staphylococci enteritis• Clostridium difficile – pseudomembranous enterocolitis
treatment - vancomycin / metronidazole• Proteus – urinary tract infection• Pseudomonas – UTI, enteritis
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Toxicity • Local irritancy
• Systemic toxicity• Aminoglycosides – ototoxicity• Chloramphenicol – bone marrow suppression• Amphotericin B – nephrotoxicity
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Hypersensitivity reactions• Rashes• Anaphylactic shock
• Sulfonamides• Penicillins• Cephalosporins
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Masking of an infection• Syphilis masked by single dose penicillin used for gonorrhea