A 55-year-old man with heart failure (EF 30%) is started on sacubitril/valsartan. The sacubitril component acts as:

• A A direct angiotensin receptor blocker more potent than valsartan alone
• B An aldosterone receptor antagonist reducing sodium retention
• C A phosphodiesterase-3 inhibitor increasing cAMP in cardiomyocytes
• D A prodrug that, after conversion to LBQ657, inhibits neprilysin — the enzyme degrading natriuretic peptides ✓

Explanation

Sacubitril is a prodrug converted by esterases to LBQ657, which inhibits neprilysin — the neutral endopeptidase that degrades natriuretic peptides (BNP, ANP), bradykinin, and other vasodilatory peptides. The resulting elevation in natriuretic peptides promotes natriuresis, vasodilation, and reduces cardiac fibrosis. Valsartan in the combination prevents the angiotensin II buildup that would otherwise occur from neprilysin inhibition alone.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.