A patient with chronic heart failure and reduced ejection fraction (HFrEF) is started on sacubitril-valsartan. The mechanism by which sacubitril enhances its cardiovascular benefit is:
- A Direct aldosterone receptor antagonism in the collecting duct
- B Inhibition of neprilysin, increasing natriuretic peptide levels ✓
- C Stimulation of guanylyl cyclase-A receptors in cardiomyocytes
- D Blockade of angiotensin-converting enzyme in pulmonary endothelium
Correct answer: B. Inhibition of neprilysin, increasing natriuretic peptide levels
Explanation
Sacubitril is a prodrug cleaved to sacubitrilat, which inhibits neprilysin (neutral endopeptidase), the enzyme that degrades natriuretic peptides (ANP, BNP), bradykinin and other vasoactive peptides. Elevated natriuretic peptides promote diuresis, natriuresis and vasodilation via particulate guanylyl cyclase. It is combined with valsartan (ARB) to prevent the hypertensive effect of accumulated angiotensin II from neprilysin inhibition.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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