A 65-year-old man with heart failure (EF 30%) is on optimal medical therapy including lisinopril and carvedilol. He develops symptomatic hypotension with each dose of carvedilol. Which property of carvedilol, compared to metoprolol, accounts for this additional haemodynamic effect?

• A Carvedilol has intrinsic sympathomimetic activity causing vasodilation
• B Carvedilol has greater beta-2 blockade causing vascular constriction and reflex hypotension
• C Carvedilol additionally blocks alpha-1 adrenoceptors, causing peripheral vasodilation ✓
• D Carvedilol inhibits phosphodiesterase, increasing cAMP-mediated vasodilation

Explanation

Carvedilol is a non-selective beta-blocker (beta-1 and beta-2) that also blocks alpha-1 adrenoceptors, producing peripheral vasodilation. This combined action is responsible for additional blood pressure lowering and can cause symptomatic hypotension, especially when combined with ACE inhibitors. Metoprolol is a selective beta-1 blocker without alpha-blocking activity. Intrinsic sympathomimetic activity (ISA), seen with pindolol, would mitigate rather than cause hypotension.

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

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