Isoniazid
Summary
Isoniazid (INH) is a first-line tuberculosis drug that inhibits mycolic acid synthesis. Major side effects include hepatotoxicity, peripheral neuropathy (prevented by B6), and drug-induced lupus.
Detail
INH is a prodrug activated by mycobacterial KatG to form INH-NAD adducts that inhibit mycolic acid synthesis. Major toxicities: hepatotoxicity (0.1-0.2%, worse >50 years and with alcohol), peripheral neuropathy (dose-related, especially in slow acetylators, prevented with pyridoxine B6 supplementation), drug-induced lupus, and seizures. Slow acetylators (NAT2 variants) accumulate INH, increasing toxicity risk. Monitor LFTs; hold if transaminases >3x ULN.
Sources
- First Aid for the USMLE Step 1
- Katzung Basic & Clinical Pharmacology
- Harrison's Principles of Internal Medicine
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