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What is A patient on anti-tubercular drug therapy developed tingling sensation on lower limb. Which of the following drug should be used for the treatment? and explain in detail?
Patient is developing tingling sensation (peripheral neuropathy) which is a side effect of Isoniazid (INH) a first line antitubercular drug. INH is extensively metabolized in liver; most impoant pathway being N-acetylation by NAT2. The acetylated metabolite is excreted in urine. The rate of INH acetylation shows genetic variation. There are either: Fast acetylators: (30-40% of Indians) t1/2 of INH 1 hr. Slow acetylators: (60-70% of Indians) t1/2 of INH 3 hr. Slow acetylators will not be able to metabolize the drug quickly and there will be accumulation of isoniazid. Isoniazid inhibits pyridoxal phosphokinase enzyme and hence causes peripheral neuritis, paraesthesias, numbness etc. Pyridoxine given prophylactically (10mg/day) prevents this neurotoxicity. On the other hand, fast acetylators are more prone to develop.