USMLE

Sacubitril

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Cardiovascular Pharm
  1. Adenosine
  2. Magnesium
  3. Nitroprusside
  4. Nitrates
  5. Ivabradine
  6. Digoxin/Digitalis
  7. Class IA Antiarrhythmics
  8. Class IB Antiarrhythmics
  9. Class IC Antiarrhythmics
  10. Class II Antiarrhythmics
  11. Class III Antiarrhythmics - Amiodarone
  12. Class III Antiarrythmics - Sotalol
  13. Class III Antiarrhythmics - Ibutilide, Dofetilide
  14. Class IV Antiarrhythmics - Verapamil, Diltiazem
  15. HMG-CoA Reductase Inhibitors (Statins)
  16. Ezetimibe
  17. Fibrates
  18. PCSK9 Inhibitors (Alirocumab, Evolocumab)
  19. Fish Oil and Omega-3s
  20. Milrinone
  21. Aliskiren
  22. Hydralazine
  23. Ranolazine
  24. Sacubitril

Summary

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