Which medication used to treat TB increases risk in slow acetylators?

• A. Isoniazid
• B. Rifampin
• C. Pyrazinamide
• D. Ethambutol

Answer: (A)

The key idea is how genetic differences in drug metabolism affect toxicity. Isoniazid is primarily cleared by the enzyme NAT2, which acetylates it. People who are slow acetylators have reduced NAT2 activity, so isoniazid stays in the body longer and at higher levels. That increased exposure raises the risk of adverse effects, especially hepatotoxicity and peripheral neuropathy. Because of this, slow acetylators are more prone to toxicity from isoniazid, and clinicians often monitor liver function and may give pyridoxine (vitamin B6) to help prevent neuropathy.

The other TB drugs—rifampin, pyrazinamide, and ethambutol—are not primarily metabolized by NAT2, so their toxicity risk isn’t specifically amplified in slow acetylators. They have their own toxicity profiles, but the increased risk tied to the slow acetylator phenotype points to isoniazid.