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Antimicrobial Agents (General Considerations)

Antimicrobial Agents (General Considerations). Prof. R. K. Dixit Pharmacology and Therapeutics K.G.M.U. Lucknow dixitkumarrakesh@gmail.com. Objectives. After this lecture you will be able to answer General adverse effects of antimicrobials

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Antimicrobial Agents (General Considerations)

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  1. Antimicrobial Agents(General Considerations) Prof. R. K. Dixit Pharmacology and Therapeutics K.G.M.U. Lucknow dixitkumarrakesh@gmail.com

  2. Objectives • After this lecture you will be able to answer • General adverse effects of antimicrobials • Specific adverse effects of important antimicrobial groups

  3. General-Adverse effects of antimicrobials • Hypersensitivity reaction- • Penicllins, Sulphonamides, Fluoroquinolones, Tetracyclines, Nitrofurantoin • Skin rashes , Angioedema, Bronchospasm • Anaphylaxis, • Management with OASIS • Oxygen, • Adrenaline {Physiological antagonist of histamine} • Antihistaminics • Steroid, • IV fluid • Supportive,

  4. Gastrointestinal symptoms- • Nausea, • Gastric irritation, • Anorexia, • Flatulence, indigestion, • Altered GI motility, • Mouth ulcers, Glossititis, Stomatitis, Chelitis • Esophagitis, • Mal-absorption syndrome • Tetracyclines, Quinolones, Ampicilline, Metronidazole

  5. Injectable Side effects- • Pain, Abscess formation, • Thrombo-phlebitis in case of IV • Flushing, redness in case of rapid IV, • Deficiency- • Vitamin B complex and Vitamin K, • Deficiency of drugs which need • entero-hepatic recirculation for their effect e.g. Oral contraceptives

  6. Superinfections New infection • Most common organisms • Pseudomonas • Candida • Proteus • Clostridium difficle- Pseudomembranous Colitis • Due to removal of inhibitory mechanisms (Bacteriocins and competition for nutrition) • Common • Clindamycin, Cotrimoxazole, Chloramphenicol, Ampicillin, Tetracyclines (CAT) • Immunosuppressant, Diabetes mellitus • Abdominal surgery Treated by Metronidazole, Vancomycin, Bacitracin

  7. CNS- • Headache, • Irritability, • Sedation, • Tinnitus , • Ataxia, • Slurred speech, • Blurring of vision, • .

  8. Masking of infections- • eg. Tt Gonorrhea mask Syphilis • Idiosyncratic and Intolerance- • Drug Fever- • Electrolyte imbalance- • Teratogenic- • No antimicrobial is absolutely safe during pregnancy • No one is Category A. • Category B, C and D can be given under special situation. • Category X absolutely contraindicated to pregnant

  9. FDA Categorization of Drugs in Pregnancy • Category A (No antibiotic is under this) • Controlled studies in women fail to demonstrate a risk • Category B (Safe can be prescribed) • Either animal-reproduction studies have not demonstrated or not confirmed in controlled studies in women • Category C (Under special circumstance) • Either studies in animals have revealed or studies in women and animals are not available. • Category D (Under special circumstance with consent) • There is positive evidence of human fetal risk, but the benefits may be acceptable despite the risk • Category X (Not prescribed) • Studies in animals or human beings have demonstrated fetal abnormalities and contraindicated

  10. Antibiotics in Pregnancy

  11. Specific Side effects of antimicrobials • Bone marrow suppression- • Chloramphenicol, • Thrombocytopenia- • Sulphonamides • Cephalosporins, (Cefamandole, Cefoperazone, Cefotetam), • Chloramphenicol • Renal toxicity- • Aminoglycosides, • Tetracyclines except Doxycycline, • Cephalothin, • Talampicillin, • Nitrofurantoin, Nalidixic acid, Amphotericin B, • Vancomycin, Ethambutol, Flucytosine, Methacillin,

  12. Hepatotoxicity- • Rifampicin, • Isoniazide (in fast acetylators due to accumulation of Acetyl – isoniazide and acetyl – hydrazine) • Pyrazinamide, Tetracycline, • Erythromycin estolate, • Talampicillin, Nalidixic acid, Trovafloxacin • Oxacillin, • Photoxicity- • Tetracyclines (Demeclocycline, Doxycycline), • Quinolones (Sparfloxacin)

  13. Ototoxicty- • Aminoglycosides, Vancomycin • Diabetes insipidus- • Demeclocycline • Neuromuscular block- • Amino-glycosides, • Polymyxin- B, Colistin (May cause respiratory paralysis in patients of Myasthenia gravis, Gaping of wound)

  14. Retinal damage- • Chloroquine • Neuropathy- • Isoniazide- more in slow acetylators • Due to increased excretion of pyridoxine in urine and • Accumulated INH inhibits pyridoxine-kinase • (Pyridoxine Kinase converts pyridoxine to active form pyridoxyl phosphate) • Polypeptide antimicrobials, • Amphotericin B, • Nitrofurantoin, • Carbenicillin

  15. Haemolysis (G-6-PD deficiency), - • X-Linked recessive. • G-6-P-D is required for regeneration of NADPH. • NADPH is required for reduction of oxidized glutathione • Reduced glutathione protects –against oxidative injury • In presence of pro-oxidants like • Naphthalene, Methylene Blue, Beans (Favism) • Drugs- Sulfa drugs, Primaquine, Isoniazide, Nitrofurantoin, Nalidixic acid, Dapsone, Furazolidione, Quinolones, Chloramphenicol, Chloroquine, Aspirin, • Haemolysis occurs S P I N Delivery G-6-P-D NADPH NADP Glutathion reductase Glutathione Glutathione disulphide

  16. Discolouration of Teeth and bone damage- • Tetracyclines • Redman (Red neck) Syndrome- • Vancomycin, Teicoplanin, • Discolouration of secretions (saliva, sweat, urine)- • Rifampicin, Clofazimine, Nitrofurantoin • Kernicterus- • Sulphonamides, Rifampicin • Flu-like syndrome- • Rifampicin • Antitestosterone effect- • Ketoconazole (reduces synthesis of testosterone and estradiol which leads to gynaecomastia)

  17. Crystaluria- • Sulphonamides • Antianabolic effect- • Tetracycllines • Cholestatic jaundice- • Erythromycin estolate, Nitrofurantoin, Fosfomycin, • Optic neuritis- • Ethambutol • Tendon rupture- • Fluroquinolones

  18. Hyperuricemia- • Pyrazinamide (Gout) • Jarisch Herxheimer Reaction- • Penicillin in syphilis • Neuromuscular blockadage- • Amino-glycosides • Alopecia- • All anti-cancer drugs • Fanconi’s Syndrome- (Renal toxicity)- • Expiry date tetracyclines- due to toxic metabolites epitetracycline • Teratogenic- • Aminoglycosides, Tetracyclines • Pulmonary eosonophilic syndrome- • Tetracylines

  19. Pseudotumor cerebri- and bulging fontanelles- • Tetracyclines • Vestibular toxicity- • Minocycline • Disulfiram like reaction – (Good Chief Minister) • Griseofulvin, • Cefoperazone, Cefotetan, Cefamandole, • Metronidazole,

  20. Grey Baby Syndrome- (Ashen Grey Cyanosis)- • Chloramphenicol • Pulmonary Fibrosis- • Bleomycin, Nitrofurantoin • Special- • Gatifloxacin • Prolongs QT interval and arrhythmia • Hypo or hyperglycemia in patients of diabetes. • Aminoglcosides have NONE side effects- • Neuromuscular block (more with Neomycin and Streptomycin), • Ototoxicity (Vestibular by Streptomycin, Gentamicin while Cochlear by Neomycin, Amikacin), • Nephrotoxicity least with Streptomycin, • Etc. Teratogenic) • High dose of Ceftriaxone • Pseudo-lithiasis (Gall bladder sludge)

  21. Mafenide • Has carbonic anhydrase inhibitor activity- • May alkalinize urine and cause acidosis • Hyperventilation. • 8-Hydroxy-quinoines (Iodochloro-hydroxyquinol,) • SMON (Subacute myelo-optic neuropathy) • Arrhythmia- • Quinolones, Macrolides • Antianabolic effect (reduce protein synthesis)- • Tetracyclines

  22. Thanks

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