Tetracyclines TETRACYCLINES AND CHLORAMPHENICOL Bacteriostatic NOT bactericidal Modified from Dr Lebreton 1 II Mechanism of antimicrobial activity competes with tRNA for the A site on 30s ribosome III Bacterial active transport system increases the intracellular concentration of antibiotic 50x more than surrounding medium This results in enhanced antibacterial activity and specificity at a dose which is harmless to animal tissues Tetracycline 2 III II Spectrum very wide includes Gram and Gram Mycoplasma Rickettsia Chamydia spp spirochaetes and some protozoa amoeba Resistance to antimicrobial activity i inhibition of protein mediated transport of antibiotic into bacterial cell ii developed resistance usually affects all tetracycline derivatives Minocycline is also effective against N meningitidis 3 IV Absorption V Distribution Oral i ready access to most tissues absorbed in GI tract mostly from stomach and upper small intestine ii cross placental barrier and enter fetal circulation and amniotic fluid absorption impaired by milk products aluminum hydroxide gels calcium and magnesium salts and iron preparations due to chelating action of tetracycline Minocycline and doxycycline are completely absorbed iii high concentration can appear in milk iv can reach significant concentrations in CSF when given I V v accumulate in dentine and enamel of unerupted teeth and in liver spleen bone marrow and bone 4 XI Side Effects VI Excretion i excreted in urine and feces ii primary route of elimination is glomerular filtration iii exceptions are minocycline which is excreted in urine to a much smaller extent and doxycycline which is not excreted in urine iv doxycycline can be of value in treating patients with impaired renal function GI irritation Phototoxicity Sun burn more particularly with demeclocycline Minocycline can produce dose related vestibular disturbances such as dizziness and nausea hepatic toxicity renal toxicity High doses of tetracycline can decrease protein synthesis in the host cellsan anti anabolic effect 5 discoloration of teeth in children drug interaction with penicillins do not use concurrently Superinfection with yeast or resistant pathogenic bacteria may occur with the tetracyclines Chloramphenicol Chloramycetin 6 II Mechanism Inhibits transpeptidases Chloramphenicol III Because of potential toxicity should be employed only in well defined and indicated conditions can also block mitochondrial protein synthesis in mammalian cells especially in erythropoetic cells 7 IV Spectrum Gram H influenzae bacteriocidal N meningitidis N gonorrhoea Salmonella typhis Brucella and Bordetella pertussis anaerobic bacteria Gram cocci clostridium Gram rods E coli V cholerae Shingella Chlamydia and Mycoplasma V Resistance i acetylation of chloramphenicol by acetyltranferase ribosome ii decreased cellular permeability iii mutation leading to ribosomal insensitivity not effective against pseudomonas histolylica Entamoeba 8 VI Absorption i parent drug readily absorbed in GI tract ii prodrug chloramphenicol palmitate hydrolyzed in duodenum iii chloramphenicol succinate used for parenteral administration V Distribution i readily accessible to tissues and bodily fluids ii high concentration achieved in brain iii enters CSF at therapeutic concentrations iv crosses placental barrier v present in milk and bile enzyme vi acetylated form cannot bind 9 VI Excretion i metabolized in liver and inactive glucuronide metabolite excreted in urine ii exercise caution in treating patients with hepatic cirrhosis iii reduced renal function can increase half life of chloramphenicol succinate VII Side effects Hematological toxicity most important side effect is on bone marrow irreversible idiosynchratic reactions aplastic anemia reversible interferes with iron metabolism Neonatal toxicity gray baby syndrome 10 Therapeutic use of antibiotics for common or important microorganisms condition microorganism Ist choice Iind choice Staphylococcus lacatamase sensitive Penicillin G or V Cephalosporin or vancomycin lacatamase insensitive lacatamase resistant penicillin flucloxacillin Cephalosporin or vancomycinor macrolide Methicillin resistant Vancomycin Ciprofloxacin or a gentamicin macrolide Gram cocci boils infection of wounds etc Penicillin G or V Cephalosporin or vancomycin an aminoglycoside septic infections e g bacteremia scarlet fever toxic shock syndrome Staphylococcus hemolytic types endocarditis Enterococcus Penicillin G gentamicin vancomycin pneumonia Pneumococcus Penicillin G or V or ampicillin or a macrolide Cephalosporin or macrolide condition microorganism Ist choice Iind choice Gram cocci sinusitis M orasella catarrhalis Amoxicillin clavulanic acid Ciprofloxacin gonorrhoea Neisseria gonorrhoea Amoxicillin clavulanic acid or ceftriaxone Cefotaxime or a quinolone meningitis Neisseria m eningitidis Penicillin V Chloramphenicol or Cefotaxime or minocycline pneumonia Pneum ococcus Penicillin G or V or ampicillin or a macrolide Cephalosporin condition microorganism Ist choice Iind choice A macrolide Penicillin V Tetanus gangrene Clostridium Penicillin V Tetracycline or a cephalosprins Rare cause of meningitis and generalized infection in neonates Amoxycillin an aminoglycoside Erythromycin an aminoglycoside Gram rods diphtheria Corynebacterium Listeria monocytogenes condition microorganism Ist choice Iind choice Gram rods Infections of urinary tract Enterobacteriaceae E coli An oral Extended spectrum Enterobacter Klebsiella Cephalosporin or a penicilin quinolone septicaemia Enterobacteriaceae E coli An Enterobacter Klebsiella aminoglycoside i v or cefuroxime Imipenem or a quinolone dysentry Shigella A quinolone Ampicillin or trimethoprim Typhoid paratyphoid Salmonella Quinolone or ceftriaxone Amoxycillin or chloramphenicol trimethoprim Infections of the respiratory tract ear sinuses meningitis Haemophillus influenzae Ampicillin or cefuroxime chloramphenicol condition microorganism Ist choice Iind choice A macrolide Ampicillin Wound infections Pasteurella multocida abscess Amoxycillin clavulanic acid Ampicillin cholera Vibrio cholerae A tetracycline A quinolone Pneumonia Legionnaires disease Legionella pneumophila A macrolide rifampicin Peptic ulcer Associated with Helicobacter pylori Amoxycillin ranitidine Metronidazole Clarithromycin methoprim Urinary tract infection Pseudomonas aeruginosa A quinolone Antipseudomonal penicillin Other infections of burns Pseudomonas aeruginosa Antipseudomonal penicillin tobramycin
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