tetracyclines, chloramphenicol, mitronidazol
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| 3 tetracyclines used mainly in clinical practice | tetracycline, doxycycline, minocycline
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| tetracyclines bind these | divalent and trivalent metal ions
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| tetracycline activity/spectrum | Bacteriostatic, broad-spectrumgram-positive; gram-negative; Spirochetes; rickettsiae; chlamydiae; mycoplasma; L-form (protoplast); Some protozoa
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| tetracycline mechanism of action | ihibit protein synthesis; Binds to 30S ribosomes, prevents tRNA binding; Relatively selective to bacteria; uptake system, energy dependent
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| mechanism of tetracycline resistance (3) | 1) enzymatic inactivation of tetracycline (rarest type) 2) efflux, a resistance gene encodes a membrane protein that actively pumps tetracycline out of the cell (** most important); 3) ribosomal protection
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| transport protein important for tetracycline resistance | TetA
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| tetracycline PKs | Absorbed from GI tract; Distributed widely to tissues and body fluid, except CSF; Bound to growing bones and teeth; Excreted in urine or/and bile depends on individual compound.
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| tetracycline SEs | Bony structures and teeth; GI functional disturbance; Liver and kidney toxicity; Photosensitization; Superinfection (esp yeast); Vestibular disturbance (minocycline)
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| tetracycline drug interactions (4) | 1) Antacids (impair the oral absorption of tets); 2) Anticonvulsant, Barbiturates, long-term alcohol use; 3) Anticoagulant, due to competition of binding/inhibition on metabolism; 4) oral contraceptives (req normal flora)
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| Tetracycline specifics | short acting; renal elimination; commonly used for acute UTI, anogenital, pharyngeal and pelvic infection.
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| Doxycycline specifics | long acting; more lipophilic and better absorption than tetracycline; Hepatic elimination; is the tetracycline of choice for many infection (no UTIs)
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| Minocycline specifics | same as doxycycline; has been widely used for the chemoprophylaxis of meningococcal disease
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| Tigecycline specifics | new class: glycylcycline, inhibits the bacterial 30S ribosome and is bacteriostatic; activity against MRSA and multi-drug resistant strains of Acinetobacter baumannii. approved for skin, soft-tissue and intrabdominal infections
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| Chloramphenicol activity | bacteria, spirochetes, rickettsia, chlamydiae, mycoplasmas
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| Chloramphenicol chemistry | very small; lipophillic; high bioavailability, distribution and absorption; very severe SEs due to mechanism
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| Chloramphenicol mechanism | Reversibly binds 50S subunit of 70S ribosome inhibitting protein synthesis; humans have 70S in mitochondria so dose-related bone marrow suppression
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| Chloramphenicol is bactericidal against these 3 common organisms causing meningitis in childhood. | H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis
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| Chloramphenicol uses | not considered first-line, but used in Childhood meningitis; Brain abscess; Richettsial infections; Typhoid fever and invasive salmonellosis
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| dose related adverse events of chloramphenicol | Gray Baby Syndrome and bone marrow suppression
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| non-dose related adverse events of chloramphenicol | Aplastic anemia
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| Metronidazole chemistry | nitroimidazole that diffuses well into all tissues, including the CNS; hydroxyl metabolite retains activity; acidic metabolite has poor activity
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| Metronidazole spectrum | active against variety of strains of protazoa and obligate anaerobes
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| Metronidazole mechanism of action | prodrug; converted in anaerobic organisms by the redox enzyme; reduced by ferredoxin; products are cytotoxic - disrupts DNA structure
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| Metronidazole resistance | Resistance develops rarely
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| Metronidazole adverse rxns | metallic taste, dark or red-brown urine; Metabolites may be mutagenic;. avoid first trimester in pregnancy.
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| Metronidazole interactions (3) | 1) no alcohol; 2)inhibits warfarin; 3) falsely low SGOT
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| Metronidazole clinical use | Clostridium species (vancomycin also works for this, but metronidazole pref by some since more narrow spectrum)
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