Milrinone is used in acute decompensated heart failure to increase cardiac contractility. Its intracellular mechanism distinguishes it from digoxin because milrinone:

• A Inhibits phosphodiesterase 3, preventing cAMP degradation in cardiomyocytes ✓
• B Inhibits Na-K ATPase, raising intracellular calcium indirectly
• C Activates adenylate cyclase directly through a Gs-coupled receptor
• D Blocks beta-adrenergic receptor internalization via beta-arrestin

Explanation

Milrinone inhibits phosphodiesterase 3, the isoform dominant in cardiac and vascular smooth muscle, so cAMP generated by endogenous beta-adrenergic stimulation is preserved. Elevated cAMP activates PKA, phosphorylating L-type calcium channels to enhance inotropy and promoting vasodilation in smooth muscle. Digoxin works entirely differently, by poisoning Na-K ATPase and raising intracellular calcium through the sodium-calcium exchanger. Milrinone does not require a receptor or G-protein, acting purely at the level of second messenger breakdown.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.