Milrinone is a positive inotrope used for acute decompensated heart failure. Its mechanism of action is:

• A Beta-1 receptor agonism increasing cAMP via Gs-coupled adenylyl cyclase activation
• B Selective inhibition of phosphodiesterase-3 (PDE-3), preventing cAMP degradation in cardiomyocytes and vascular smooth muscle ✓
• C Activation of myosin light chain kinase via calmodulin-independent pathway
• D Cardiac glycoside-like Na+/K+-ATPase inhibition increasing intracellular calcium

Explanation

Milrinone is a bipyridine phosphodiesterase-3 (PDE-3) inhibitor — a 'non-glycoside, non-catecholamine positive inotrope' also called an inodilator. PDE-3 is the predominant cAMP-hydrolyzing enzyme in cardiomyocytes and vascular smooth muscle. By inhibiting PDE-3, milrinone increases cAMP levels in cardiomyocytes (enhancing L-type calcium channel activity, increasing contractility) and in vascular smooth muscle (activating PKA → MLCK inhibition, causing vasodilation). The combined inotropic and vasodilatory (pulmonary and systemic) effects reduce preload, afterload, and improve cardiac output, particularly useful in cardiogenic shock with high SVR.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.