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TETRACYCLINES Mechanism of action Inhibit protein synthesis by binding reversibly to 30 s subunit Short acting Tetracycline Oxytetracycline t1/2 6-8 hr Intermediate Demeclocycline Methacycline t1/2 12 hr Long acting Doxycycline Minocycline t1/2 16-18 hr
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Tetracyclines ( Cont. ) Antibacterial activity Broad spectrum antibiotics > G+ bacteria Chlamydia V. cholera Rickettsiae Brucella Mycoplasma H. pylori
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Tetracyclines ( Cont. ) Pharmacokinetics Usually given orally Absorption adequate but incomplete ( except doxy- & mino- cycline 90-100% ) Absorbed in the upper s. intestine & best in absence of food Food & di & tri-valent cations ( Ca, Mg, Fe, AL) impair absorption Protein binding 40-80 % Distributed well, except CSF. Exception : minocycline,doxycycline Cross placenta and excreted in milk Excretion – bile-10-40% ( enterohepatic)and kidney-10-50%. Exception : doxycycline-Largely metabolized in the liver
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Tetracyclines ( Cont. ) Clinical uses 1. Rickettsial infections – Drug of choice 2. Chlamydial infection – Drug of choice 3. Mycoplasma pneumonia – Drug of choice 4. Bacillary infections Brucellosis in combination with rifampin or streptomycin - Drug of choice Cholera - Drug of choice 5. Traveller’s diarrhea 6. H.pylori ( in combination with bismuth & metronidazole or clarithromycin ). 7. Miscellaneous - Acne
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Tetracyclines ( Cont. ) Side effects 1. nausea, vomiting and diarrhea 2. Thrombophlebitis – i.v 3. Phototoxicity ( systemic administration) – low incidence 4. Hepatic toxicity ( prolonged therapy with high dose ) 5. Kidney toxicity (duration & dose related)( except,doxycycline) 6. Brown discolouration of teeth – children 7. Deformity or growth inhibition of bones – children 8. Vertigo – minocycline(200-400mg/d)& doxycycline 100mg/d 9. Suprainfection
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