Which pharmacogenomic variation is most clinically relevant when prescribing metoprolol in a patient who reports excessive bradycardia at standard doses?

• A CYP2C9 poor metabolizer status
• B UGT1A1 polymorphism causing reduced glucuronidation
• C P-glycoprotein overexpression reducing CNS penetration
• D CYP2D6 poor metabolizer status ✓

Explanation

Metoprolol is extensively metabolized by CYP2D6. CYP2D6 poor metabolizers (approximately 7–10% of Caucasians, lower prevalence in Asians) accumulate much higher plasma concentrations at standard doses, leading to excessive bradycardia, hypotension, and fatigue. CYP2C9 is not primarily involved in metoprolol metabolism. UGT1A1 affects drugs like irinotecan and bilirubin conjugation. P-gp affects CNS penetration but not the degree of beta-blockade for metoprolol's cardiac effects.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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