A 28-year-old woman with newly diagnosed pulmonary TB is started on RHZE. Her acetylator status is tested and she is found to be a slow acetylator. Which statement is correct regarding this finding?

• A She has higher risk of rifampicin-induced orange discoloration of body fluids
• B She has higher risk of isoniazid-induced hepatotoxicity and peripheral neuropathy ✓
• C She requires a higher dose of isoniazid to achieve therapeutic levels
• D She is more likely to develop pyrazinamide-induced hyperuricaemia

Explanation

Slow acetylators (homozygous for NAT2 slow alleles) have reduced clearance of isoniazid, leading to higher plasma levels. This increases risk of dose-dependent toxicities: hepatotoxicity (via accumulation of acetylhydrazine) and peripheral neuropathy (via pyridoxine depletion). Routine acetylator testing is not recommended in current guidelines as standard dosing is safe for both phenotypes, but the concept is frequently tested in Indian PG exams.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.