Sacubitril/valsartan (LCZ696) reduces mortality in HFrEF. The sacubitril component acts as a prodrug; its active metabolite LBQ657 inhibits which enzyme?

• A Angiotensin-converting enzyme (ACE)
• B Renin
• C Neprilysin (neutral endopeptidase, NEP) ✓
• D Aldosterone synthase (CYP11B2)

Explanation

Sacubitril is a prodrug converted to LBQ657, which inhibits neprilysin (neutral endopeptidase NEP). Neprilysin degrades natriuretic peptides (ANP, BNP), bradykinin, and adrenomedullin. Inhibiting neprilysin increases these beneficial vasoactive peptides, reducing preload and afterload. Combined with valsartan (ARB) to block angiotensin II, the combination reduces hospitalization and cardiovascular death in HFrEF. It is contraindicated with ACE inhibitors due to risk of angioedema.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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