A patient receiving isoniazid (INH) for tuberculosis develops peripheral neuropathy. The mechanism is:

• A INH directly demyelinates peripheral nerves via oxidative stress
• B INH inhibits folate absorption in the intestine
• C INH causes mitochondrial DNA depletion in Schwann cells
• D INH inhibits pyridoxal kinase and forms hydrazone complexes with pyridoxal phosphate (PLP), causing functional vitamin B6 deficiency ✓

Explanation

INH forms a stable hydrazone complex with pyridoxal-5-phosphate and also inhibits pyridoxal kinase (which converts pyridoxine to PLP), causing functional vitamin B6 deficiency; PLP is the coenzyme for aminotransferases, decarboxylases (including DOPA decarboxylase), and transsulfuration enzymes — its deficiency produces peripheral neuropathy and sideroblastic anaemia. Pyridoxine 25 mg/day is co-administered to prevent this. Folate and mitochondrial DNA are not the INH targets.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.