Pharmacogenomic testing reveals that a patient is a CYP2D6 ultra-rapid metabolizer. Which pharmacodynamic consequence is most relevant when prescribing metoprolol for hypertension in this patient?
- A Increased risk of metoprolol-induced bronchoconstriction due to drug accumulation
- B Markedly reduced plasma levels leading to inadequate beta-1 blockade and poor blood pressure control ✓
- C Conversion of metoprolol to a toxic reactive intermediate by CYP2D6
- D Enhanced beta-2 stimulation causing paradoxical tachycardia
Correct answer: B. Markedly reduced plasma levels leading to inadequate beta-1 blockade and poor blood pressure control
Explanation
Metoprolol is extensively metabolised by CYP2D6; ultra-rapid metabolisers (gene duplication, e.g. CYP2D6*1xN) achieve 3–5-fold lower plasma concentrations than extensive metabolisers, resulting in sub-therapeutic beta-1 blockade and inadequate antihypertensive effect. The opposite — poor metabolisers — accumulate metoprolol and risk bradycardia/bronchospasm. There is no significant toxic reactive intermediate from CYP2D6 for metoprolol.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.