A 35-year-old HIV-negative patient with newly diagnosed pulmonary tuberculosis is started on first-line DOTS therapy. After 2 months of treatment, he develops bilateral foot drop and paraesthesia in the hands. Which drug is responsible, and what is the mechanism?

• A Rifampicin — inhibits bacterial RNA polymerase causing axonal demyelination
• B Isoniazid — inhibits pyridoxal phosphokinase, causing pyridoxine deficiency and peripheral neuropathy ✓
• C Pyrazinamide — inhibits fatty acid synthesis in neural tissue
• D Ethambutol — chelates zinc required for nerve conduction

Explanation

Isoniazid (INH) inhibits the enzyme pyridoxal phosphokinase, preventing conversion of pyridoxine (vitamin B6) to its active coenzyme form pyridoxal phosphate. This causes a peripheral sensorimotor neuropathy, especially in slow acetylators and malnourished patients. Prophylactic pyridoxine 10 mg/day prevents this complication. Ethambutol causes optic neuritis (retrobulbar), not peripheral neuropathy. Rifampicin's mechanism of inhibiting bacterial DNA-dependent RNA polymerase does not directly affect mammalian nerves.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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