A patient on long-term isoniazid therapy develops peripheral neuropathy. The mechanism relates to isoniazid's interference with which vitamin pathway?
- A Isoniazid forms a hydrazone complex with pyridoxal phosphate (PLP), depleting active B6 and impairing PLP-dependent neurotransmitter synthesis ✓
- B Isoniazid depletes folate by inhibiting dihydrofolate reductase
- C Isoniazid inhibits vitamin B12 absorption in the terminal ileum
- D Isoniazid increases oxidative stress depleting vitamin E in peripheral nerves
Explanation
Isoniazid (INH) is a structural analogue of nicotinamide and forms a covalent hydrazone with pyridoxal phosphate (PLP), the active form of vitamin B6. The INH-PLP complex is pharmacologically inactive and is excreted, functionally depleting PLP. PLP is the essential cofactor for DOPA decarboxylase (dopamine synthesis), aromatic amino acid decarboxylase (serotonin synthesis), GABA transaminase, cystathionine beta-synthase, and many other reactions. In neurons, PLP depletion impairs these pathways and contributes to peripheral neuropathy. Co-administration of pyridoxine 25–50 mg/day prevents this toxicity. Folate inhibition is the mechanism of methotrexate and trimethoprim, not INH.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.