A 30-year-old man develops peripheral neuropathy on isoniazid therapy. The MECHANISM of this toxicity and its prevention:

• A Isoniazid chelates calcium from myelin sheaths; calcium supplementation prevents neuropathy
• B Toxic acetylhydrazine metabolite accumulates in neurons; N-acetylcysteine prevents neuropathy
• C Isoniazid induces CYP450 in Schwann cells; rifampicin prevents this by competing for CYP binding
• D Isoniazid inhibits pyridoxine phosphokinase; pyridoxine supplementation prevents neuropathy ✓

Explanation

Isoniazid competes with pyridoxal phosphate (active vitamin B6) for the enzyme pyridoxine phosphokinase, and it also combines directly with pyridoxal to form inactive hydrazones, depleting active vitamin B6. Pyridoxal phosphate is essential for the synthesis of GABA (glutamate decarboxylase) and other neurotransmitters. Depletion causes sensory peripheral neuropathy, especially in slow acetylators, malnourished patients, alcoholics, and pregnant women who have higher pyridoxine requirements. Prophylactic pyridoxine (10–50 mg/day) prevents this complication. Acetylhydrazine metabolite (from isoniazid hydrolysis) causes hepatotoxicity, not neuropathy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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