Two patients take identical doses of isoniazid. Patient X is a rapid acetylator (NAT2 fast metabolizer) and Patient Y is a slow acetylator. Which pairing of genotype and characteristic toxicity risk is correct?

• A Rapid acetylators have higher risk of peripheral neuropathy
• B Slow acetylators have higher risk of hepatotoxicity
• C Rapid acetylators have higher risk of isoniazid-induced hepatitis ✓
• D Acetylator status affects neither neuropathy nor hepatitis risk

Explanation

Rapid acetylators convert isoniazid to acetylisoniazid quickly, generating more monoacetylhydrazine, the hepatotoxic metabolite, so they carry a higher risk of hepatitis. Slow acetylators sustain higher plasma concentrations of unmetabolized isoniazid, which increases their risk of peripheral neuropathy. This reciprocal relationship between the two phenotypes is the discriminating fact examined here.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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