Pharmacogenomics: A patient with CYP2D6 poor metaboliser status is prescribed metoprolol. The expected clinical consequence is:

• A Sub-therapeutic metoprolol levels requiring dose escalation
• B Exaggerated and prolonged beta-blockade with bradycardia ✓
• C Increased formation of active hydroxylated metabolite
• D Conversion of metoprolol to cardiotoxic quinone metabolite

Explanation

Metoprolol is primarily metabolised by CYP2D6 to alpha-hydroxymetoprolol, an inactive metabolite. In CYP2D6 poor metabolisers, this elimination pathway is absent, leading to markedly elevated metoprolol plasma concentrations and pronounced, prolonged beta-1 blockade — clinically manifest as severe bradycardia and hypotension. Dose reduction is required in such individuals. The active metabolite concept (option C) is reversed here — the parent drug accumulates.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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