Hydralazine causes lupus-like syndrome with chronic use. The pharmacogenomic factor that predicts this adverse effect is:
- A Poor metabolizer status for CYP2D6
- B HLA-B*5701 carrier status
- C Slow acetylator phenotype of N-acetyltransferase 2 (NAT2) ✓
- D G6PD deficiency
Explanation
Hydralazine is acetylated by NAT2 in the liver. Slow acetylators (who have reduced NAT2 activity, more common in Caucasians) accumulate higher levels of hydralazine and its reactive metabolites, which form adducts with histones and trigger drug-induced lupus erythematosus (DILE). Slow acetylators have a 5-10 times higher risk of developing DILE with hydralazine than fast acetylators. The acetylator phenotype also affects the toxicity of isoniazid (peripheral neuropathy higher in slow acetylators) and procainamide (another drug that causes DILE predominantly in slow acetylators). HLA-B*5701 is linked to abacavir hypersensitivity.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.