Sacubitril is an antihypertensive medication used for treatment of heart failure. It works by inactivating neprilysin, a compound that normally inhibits peptides such as ANP, BNP, and angiotensin II. This ultimately will increase the amounts of these peptides, resulting in vasodilation , natriuresis, and diuresis, effectively reducing blood pressure as well as the volume load on the heart. Adverse effects include hypotension, dizziness, and is contraindicated with the use of ace inhibitors due to exacerbation of side effects such as angioedema.

Key Points

  • Sacubitril
    • Mechanism
      • Inhibits neprilysinincreases ANP
        • Neprilysn is an endogenous endopeptidase that breaks down and inactivates various peptide hormones
        • Also increases levels of BNP, angiotensin II, bradykinin, glucagon, substance P, etc
          • So lots of random side effects
    • Clinical Use
      • Heart Failure with Reduced Ejection Fraction (HFrEF)
        • Increased ANP leads to decreased BP through peripheral vasodilation (blood vessels), natriuresis (inhibiting aldosterone secretion by adrenals), and diuresis (dilates afferent arterioles → increased GFR)
    • Adverse Effects
      • Increases angioedema risk for ACE inhibitors
        • Contraindicated with ACE inhibitors
      • Hypotension
      • Hyperkalemia
      • Cough
      • Dizziness