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Drug interaction: it induces cytochrome p450 isoenzyme, it hasten metabolism of oral contraceptives, warfarin, protease inhibitors for HIV infection. oIsoniazid: MOA: highly selective for M.tuberculosis and kill tubercle bacilli at concentration 10,000 x lower than those needed to affect gram + or gram – bacteria. Tubercle bacilli can develop resistance to isoniazid so multi-drug therapy is recommended to decrease resistance. Therapeutic use: it is indicated for treating active and latent TB. For latent, it is given alone or with rifapentine. But for active, combined with other agent such as rifampin. Adverse effect: Hepatotoxicity, same as above. Also remember that the younger you are the less the risk for liver damage. Hepatitis signs (anorexia, malaise, fatigue, nausea, yellow of skin,eyes). Monthly check ALT, AST. Also causes peripheral neuropathyInteraction: it is a strong inhibitor of 3 Cytochromes P450 (cypc9, cyp2c19,cyp2e1). By inhibiting these isoenzymes, it can raise the levels of (phenytoin,carbamazepine,diazepam, triazolam.) oPyrazenamide: MOA: bacteriocidal to M.tubercuslos. currently used as combination therapy with rifampin, isoniazid, and ethambutol. The rest just like above.Adverse effects: Hepatoxicity; liver injury with high dose therapybut not hepatic necrosis. The earliest manifestation of liver damage is elevated AST and ALT. liver injury with concurrent therapy. Nongouty polyarthralgia, hyperuricemia, gout (rare), nausea, vomiting, rash, photosensitivity. oEthambutol:MOA: active only against mycobacteria; nearly all strains of M.tuberculosis are sensitive. This drug is bacteriostatic. For
initial treatment of TB and for those who have received treatmentpreviously.It is given as multidrug regimen. Adverse reaction: Optic Neuritis: dose related optic neuritis; blurred vision, constriction of visual field, color discrimination issue. Symptoms resolve with discontinuation of trea’t. Asymptomatic hyperuricemia in 50% of pts with elevated uric acid and gouty arthritis. B.Understand that majority of the drugs (which drugs?) within drug regimen used for active TB can cause hepatotoxicity and it is expected to have elevated LFT levels due tothe benefits of drug treatment for this multi-drug resistant infection. What are the common drugs used in active TB; what should be monitored and major ADRs for each drug.