Milrinone PDE3 Mechanism — EECC MCQ

Correct answer: D — Milrinone is a phosphodiesterase-3 (PDE3) inhibitor that increases intracellular cAMP in cardiomyocytes (positive inotropy) and vascular smooth muscle (vasodilation — reducing preload and afterload); it is an 'inodilator' with no beta-receptor dependency

Milrinone (and enoximone) are PDE3 inhibitors — they prevent the breakdown of cAMP, increasing its intracellular concentration. Effects: (1) In cardiomyocytes: increased cAMP → increased PKA → increased calcium channel phosphorylation → increased contractility (positive inotropy) + increased lusitropy (improved relaxation); (2) In vascular smooth muscle: increased cAMP → vasodilation (both arterial and venous — reducing afterload and preload). This 'inodilator' profile is particularly useful in: (1) patients already on beta-blockers (milrinone's effect is independent of beta-receptors, unlike dobutamine which acts on beta-1); (2) RV failure (afterload reduction); (3) post-cardiac surgery low output. The ESC HF Guidelines include milrinone as a short-term inotropic option (Class IIb) for acute HF with low output. Adverse effects: hypotension, arrhythmias (increased cAMP is pro-arrhythmic), thrombocytopenia.

Reference: ESC (2023): HF Guidelines