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MICABI - Exam 1

tetracyclines, chloramphenicol, mitronidazol

3 tetracyclines used mainly in clinical practice tetracycline, doxycycline, minocycline
tetracyclines bind these divalent and trivalent metal ions
tetracycline activity/spectrum Bacteriostatic, broad-spectrumgram-positive; gram-negative; Spirochetes; rickettsiae; chlamydiae; mycoplasma; L-form (protoplast); Some protozoa
tetracycline mechanism of action ihibit protein synthesis; Binds to 30S ribosomes, prevents tRNA binding; Relatively selective to bacteria; uptake system, energy dependent
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
transport protein important for tetracycline resistance TetA
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.
tetracycline SEs Bony structures and teeth; GI functional disturbance; Liver and kidney toxicity; Photosensitization; Superinfection (esp yeast); Vestibular disturbance (minocycline)
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)
Tetracycline specifics short acting; renal elimination; commonly used for acute UTI, anogenital, pharyngeal and pelvic infection.
Doxycycline specifics long acting; more lipophilic and better absorption than tetracycline; Hepatic elimination; is the tetracycline of choice for many infection (no UTIs)
Minocycline specifics same as doxycycline; has been widely used for the chemoprophylaxis of meningococcal disease
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
Chloramphenicol activity bacteria, spirochetes, rickettsia, chlamydiae, mycoplasmas
Chloramphenicol chemistry very small; lipophillic; high bioavailability, distribution and absorption; very severe SEs due to mechanism
Chloramphenicol mechanism Reversibly binds 50S subunit of 70S ribosome inhibitting protein synthesis; humans have 70S in mitochondria so dose-related bone marrow suppression
Chloramphenicol is bactericidal against these 3 common organisms causing meningitis in childhood. H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis
Chloramphenicol uses not considered first-line, but used in Childhood meningitis; Brain abscess; Richettsial infections; Typhoid fever and invasive salmonellosis
dose related adverse events of chloramphenicol Gray Baby Syndrome and bone marrow suppression
non-dose related adverse events of chloramphenicol Aplastic anemia
Metronidazole chemistry nitroimidazole that diffuses well into all tissues, including the CNS; hydroxyl metabolite retains activity; acidic metabolite has poor activity
Metronidazole spectrum active against variety of strains of protazoa and obligate anaerobes
Metronidazole mechanism of action prodrug; converted in anaerobic organisms by the redox enzyme; reduced by ferredoxin; products are cytotoxic - disrupts DNA structure
Metronidazole resistance Resistance develops rarely
Metronidazole adverse rxns metallic taste, dark or red-brown urine; Metabolites may be mutagenic;. avoid first trimester in pregnancy.
Metronidazole interactions (3) 1) no alcohol; 2)inhibits warfarin; 3) falsely low SGOT
Metronidazole clinical use Clostridium species (vancomycin also works for this, but metronidazole pref by some since more narrow spectrum)
Created by: Krafty