Transcript Antimicrobial Agents (General Considerations 2 )

Antimicrobial Agents
(General Considerations)
Prof. R. K. Dixit
Pharmacology and Therapeutics
K.G.M.U. Lucknow
[email protected]
Objectives
• After this lecture you will be able to answer
– General adverse effects of antimicrobials
– Specific adverse effects of important antimicrobial
groups
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,
•Gastrointestinal symptoms•Nausea,
•Gastric irritation,
•Anorexia,
•Flatulence, indigestion,
•Altered GI motility,
•Mouth ulcers, Glossititis, Stomatitis, Chelitis
•Esophagitis,
•Mal-absorption syndrome
•Tetracyclines, Quinolones, Ampicilline,
Metronidazole
•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
Superinfections
New infection
• Most common organisms
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Pseudomonas
Candida
Proteus
Clostridium difficle- Pseudomembranous Colitis
Due to removal of inhibitory mechanisms
(Bacteriocins and competition for nutrition)
–
Common
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Clindamycin, Cotrimoxazole, Chloramphenicol,
Ampicillin, Tetracyclines (CAT)
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Immunosuppressant, Diabetes mellitus
Abdominal surgery
Treated by Metronidazole, Vancomycin, Bacitracin
•CNS•Headache,
•Irritability,
•Sedation,
•Tinnitus ,
•Ataxia,
•Slurred speech,
•Blurring of vision,
•.
•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
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
Antibiotics in Pregnancy
FDA Category
Antibiotics in Category
A
B
Penicillins, Cephalosporins, Carbapenems (except Imipenem),
Daptomycin, Vancomycin (oral), Clindamycin, Erythromycin,
Azithromycin, Metronidazole (avoid first trimester), Nitrofurantoin,
Acyclovir, Amphoterocin B, Ethambutol
C
Quinolones, Chloramphenicol, Clarithromycin, Imipenem, Linezolid,
Trimethoprim/Sulfa (D if used near term), Vancomycin (IV), Rifampin,
INH, PZA, PAS, Fluconazole, Caspofungin
D
Tetracyclines (Doxy, Tige, Mino), Voriconazole, Aminoglycosides (some
put gentamicin as a category C)
X
Ribavarin
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,
•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)
•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)
•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
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,
S
P
•Haemolysis occurs
I
N
Delivery
G-6-P-D
NADPH
NADP
Glutathion reductase
Glutathione
Glutathione disulphide
•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)
•Crystaluria•Sulphonamides
•Antianabolic effect•Tetracycllines
•Cholestatic jaundice•Erythromycin estolate, Nitrofurantoin, Fosfomycin,
•Optic neuritis•Ethambutol
•Tendon rupture•Fluroquinolones
•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
•Pseudotumor cerebri- and bulging fontanelles•Tetracyclines
•Vestibular toxicity•Minocycline
•Disulfiram like reaction – (Good Chief Minister)
•Griseofulvin,
•Cefoperazone, Cefotetan, Cefamandole,
•Metronidazole,
•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)
•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
Thanks