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AntiMtb Drugs
lecture 24 goodman
| Question | Answer |
|---|---|
| MDR Mtb | multi-drug resistant Mtb - resistant to isoniazid (INH) and rifampin |
| XDR Mtb | extra-drug resistant Mtb - resistant to INH, rifampin, fluoroquinolones and @ least one injectable 2nd line drug (aminoglycosides or capreomycin) |
| When does single drug therapy suffice? | when pt is asymptomatic with a (+) PPD - prophylaxis in latent phase |
| RIPE therapy, first-line drugs | rifampin, isoniazid, pyrazinamide and ethambutol (or streptomycin). once drug sensitivity is known, may drop it down to 3 for @ least 2 months |
| protocol for treating active TB | first 2 mo: isoniazid, rifampin and pyrazinamide (initial phase)THEN next 4 mo: just isoniazid and rifampin (continuation phase) |
| how to treat prophylactically those who are in households with TB contact, recently converted PPD (+) or inadequately treated old inactive cases | isoniazid for 6 mo |
| INH mechanism of action | bactericidal or -static, prodrug that must be activated by Mtb catalase-peroxidase into reactive radical that makes adducts that block DHFR and stop mycolic acid synthesis |
| INH pharmacokinetics | well-absorbed and distributed. it's inactivated by acetylation, but 50% of pts will have slow acetylation enzyme = toxic accumulation of drug if kidney function is impaired |
| adverse effects of INH | peripheral & optical neuropathy caused by "vitB6 deficiency-like" syndrome (INH is a competitive analog); hepatic toxicity (multilobular necrosis) especially in > 50 y/o |
| rifampin | RNA polymerase inhibitor, give with INH whenever possible, turns all bodily secretions orange, potent inducer of P450s! |
| pyrazinamide | stops protein synthesis in growing bacteria & disallows trans-translation of semi-dormant ones. adverse effect: hepatic damage in 15% of pts, inhibits urate secretion |
| ethambutol | stops the first step in cell wall synthesis - arabinose incorporation. causes optic neuritis in up to 15% of pts (check visual acuity and color differentiation!) |
| streptomycin | IV aminoglycoside that causes mRNA misreading/incorporation of mutated proteins into the PM which lyses cell from ion leakage. adverse effects: oto- and nephrotoxicity, may block the NMJ in susceptible pts |
| moxifloxacin | fluoroquinolone that may be new 1st line Mtb drug, binds DNA gyrase/topoisomerase to stop DNA transcription & replication. may weaken cartilage in children or cause phototoxicity. NO milk or antacids. |
| drugs for MAC infection, especially in AIDS pts | clarithromycin, azithromycin (macrolides) or rifabutin |
| macrolide (clarithro-/azithromycin) mechanism of action | bind 23S RNA in the 50S subunit and block the peptide export channel |
Created by:
sirprakes
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