An epileptic patient stabilised on phenytoin starts anti-TB therapy. Two weeks later she develops ataxia and nystagmus, and her INH level is found to be low. The most likely explanation is:

• A She is a slow acetylator, so INH accumulates competitively displacing phenytoin
• B Rifampicin has induced metabolism of both drugs
• C She is a rapid acetylator, and INH inhibits phenytoin metabolism causing toxicity despite low INH levels ✓
• D Ethambutol has displaced phenytoin from plasma proteins

Explanation

INH is inactivated mainly by N-acetyltransferase 2 (NAT2), producing fast and slow acetylator phenotypes. INH inhibits the metabolism of phenytoin, raising phenytoin levels and causing cerebellar toxicity regardless of acetylator status. Rapid acetylators clear INH quickly, explaining her low INH level, yet the inhibition of phenytoin hydroxylation persists. Rifampicin induces rather than inhibits metabolism.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.