A 55-year-old with hypertension is started on sacubitril/valsartan (Entresto). Sacubitril works by inhibiting neprilysin. Which of the following peptides most accurately summarizes the substrates whose degradation is inhibited by neprilysin?
- A BNP, ANP, adrenomedullin, substance P, bradykinin — vasodilatory and natriuretic peptides ✓
- B Angiotensin II and aldosterone — vasoconstrictive hormones
- C Endothelin-1 and thromboxane A2 — vasoconstrictors
- D Renin and ACE — components of RAAS pathway
Explanation
Neprilysin is a neutral endopeptidase that degrades multiple vasoactive peptides including natriuretic peptides (ANP, BNP, CNP), bradykinin, adrenomedullin, and substance P. Inhibiting neprilysin with sacubitril preserves these endogenous vasodilatory and natriuretic peptides, reducing preload, afterload, and fibrosis. Because neprilysin also degrades angiotensin I/II, sacubitril must always be co-administered with an ARB (valsartan) to prevent accumulation of angiotensin II; ACE inhibitors are contraindicated with sacubitril due to severe angioedema risk from excess bradykinin.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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