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Milrinone Mechanism — FRCA Primary MCQ

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HardPharmacology - CardiovascularMilrinone MechanismFRCA Primary

A patient with low cardiac output remains poorly responsive to dobutamine because of chronic beta-blockade. Milrinone improves stroke volume but causes hypotension. Which mechanism best accounts for both effects?

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Correct answer: D — Phosphodiesterase-3 inhibition raises cAMP in myocardium and vascular smooth muscle

The best answer is “Phosphodiesterase-3 inhibition raises cAMP in myocardium and vascular smooth muscle”. Milrinone inhibits PDE3, reducing cAMP breakdown. Increased myocardial cAMP augments calcium handling and inotropy, while increased vascular-smooth-muscle cAMP causes vasodilation and hypotension. Unlike dobutamine it does not require beta1-receptor stimulation. Digoxin inhibits Na+/K+-ATPase, and alpha1 agonism produces vasoconstriction rather than the characteristic inodilator profile.

Reference: RCoA, Primary FRCA syllabus: https://www.rcoa.ac.uk/sites/default/files/documents/2026-01/Primary-FRCA-Syllabus.pdf; Cardiac Cyclic Nucleotide Phosphodiesterases: https://pmc.ncbi.nlm.nih.gov/articles/PMC4114334/