Slow acetylators of isoniazid are more prone to develop:
Isoniazid is the antitubercular drug parexcellence, and an essential component of all antitubercular regimens, unless the patient is not able to tolerate it or bacilli are resistant. lt is primarily tuberculocidal. Fast multiplying organisms are rapidly killed, but quiescent ones are only inhibited. It acts on extracellular as well as on intracellular TB (bacilli present within macrophages); is equally active in acidic and alkaline medium. It is one of the cheapest antitubercular drugs. However, most atypical mycobacteria are not inhibited by INH. Peripheral neuritis and a variety of neurological manifestations (paresthesias, numbness, mental disturbances, rarely convulsions) are the most impoant dose-dependent toxic effects. These are due to interference with utilization of pyridoxine and its increased excretion in urine.Pyridoxine given prophylactically 1 10 mg I day) prevents the neurotoxicity even with higher doses, but routine use is not mandatory. INH neurotoxicity is treated by pyridoxine 100 mg/day.INH is completely absorbed orally and penetrates all body tissues, tubercular cavities, placenta and meninges. It is extensively metabolized in liver; most impoant pathway being acetylation-metabolites are excreted in urine. The rate of INH acetylation shows genetic variation. There are either: Fast acetylators (30--40% of Indians) Ph of INH 1 hr. Slow acetylators (60-70% of Indians) flh of INH 3 hr_ The propoion of fast and slow acetylators differs in different pas of the world. However, acetylator status does not matter if INH is taken daily, but biweekly regimens are less effective in fast acetylators. Isoniazid induced peripheral neuritis appears to be more common in slow acetylators. ESSENTIALS OF MEDICAL PHARMACOLOGY T.D.TRIPATHI SIXTH EDITION Page No:740,741
Failure of therapy
Peripheral neuropathy
Hepatotoxicity
Allergic reactionsl
Chemotherapy