Sacubitril-valsartan is used in HFrEF. The component sacubitril acts by:
- A Inhibiting neprilysin, an endopeptidase that degrades natriuretic peptides, bradykinin, and substance P ✓
- B Blocking angiotensin II type 1 (AT1) receptors, preventing vasoconstriction and aldosterone release
- C Inhibiting angiotensin-converting enzyme, preventing angiotensin I to II conversion
- D Activating guanylate cyclase in vascular smooth muscle cells, producing vasodilation
Correct answer: A. Inhibiting neprilysin, an endopeptidase that degrades natriuretic peptides, bradykinin, and substance P
Explanation
Sacubitril is a prodrug (converted to LBQ657) that inhibits neprilysin (neutral endopeptidase 24.11), which normally degrades natriuretic peptides (ANP, BNP), bradykinin, and other vasoactive peptides. Inhibiting neprilysin increases natriuretic peptide levels, promoting natriuresis, diuresis, and vasodilation. It is combined with valsartan (AT1 blocker) to prevent the concurrent angiotensin II rise from neprilysin inhibition; the combination reduces mortality in HFrEF.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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