A patient on anti-TB therapy develops peripheral neuropathy. The biochemical mechanism of isoniazid-induced neuropathy is:

• A Direct demyelination by reactive oxygen species generated during INH activation
• B Inhibition of mycolic acid synthesis in peripheral Schwann cells
• C Competitive inhibition of pyridoxal kinase, depleting active pyridoxal 5'-phosphate (PLP) ✓
• D Chelation of intracellular magnesium by INH hydrazide moieties

Explanation

Isoniazid (INH) and its metabolites compete with pyridoxal phosphate (PLP) for pyridoxal kinase and pyridoxine phosphate oxidase, both needed to generate active PLP (vitamin B6). PLP is an essential cofactor for aminotransferases and decarboxylases involved in neurotransmitter synthesis (GABA, serotonin, dopamine). PLP deficiency disrupts axonal transport proteins and causes peripheral neuropathy, prevented by co-administration of pyridoxine 10–25 mg/day.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.