Lecture on ACE Inhibitors, ARBs, and ARNIs

Objectives

• Describe the usage and effects of ACE inhibitors, ARBs, and ARNIs.
• Understand how they affect cardiac status and care.

Overview of ACE Inhibitors and ARBs

• Vasodilator Drugs: Mixed vasodilators affecting both arterial and venous systems.

The RAS System (Renin-Angiotensin-Aldosterone System)

• Activated via kidneys when lower glomerular filtration pressure is detected.
• Increases water retention and vasoconstriction to maintain kidney perfusion.
• Key Components:
  • Renin converts angiotensinogen to Angiotensin I.
  • ACE converts Angiotensin I to Angiotensin II.
  • Angiotensin II stimulates AT1 receptors causing:
    • Vasoconstriction
    • Increased aldosterone
    • Increased sodium retention
    • Increased sympathetic activity

ACE Inhibitors

• Function: Block ACE from converting Angiotensin I to Angiotensin II.
  • Prevent stimulation of AT1 receptors.
  • Prevent breakdown of bradykinin.
• Effects:
  • Fail to increase aldosterone, sodium and water retention, vasoconstriction, and sympathetic activity.
• Groups of ACE Inhibitors:
  • Class 1: Captopril and similar agents.
  • Class 2: Water-soluble agents like linil.
  • Class 3: Prodrugs like enalopril activated after hepatic metabolism.

Indications for ACE Inhibitor Therapy

• Heart failure (all stages)
• Hypertension (especially high-risk patients)
• Diabetes and proteinuria
• Early phase acute MI
• Left ventricular dysfunction

Mechanism and Effects

• Reduce afterload and preload, and increase cardiac output.
• Dual vasodilatory effect:
  • Block formation of Angiotensin II.
  • Block degradation of bradykinin.
• Adverse Effects:
  • Hypotension, renal failure, hyperkalemia.
  • ACE inhibitor-induced cough, angioedema, rash.

Angiotensin II Receptor Blockers (ARBs)

• Function: Block AT1 receptor, preventing Angiotensin II from exerting effects.
• Effects: Similar to ACE inhibitors but do not cause cough due to bradykinin breakdown.
• Indications: Used when ACE inhibitors are not tolerated.
• Adverse Effects: Hypotension, renal failure, hyperkalemia.

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• Function: Combination of ARB and neprilysin inhibitor.
  • Block breakdown of natriuretic peptides, prolonging vasodilatory effects.
• Indications: Heart failure with reduced ejection fraction, persistent NYHA Class 2 or 3 symptoms despite other therapies.

Conclusion

• ARBs avoid ACE inhibitor-induced cough because they do not inhibit the breakdown of bradykinin.

Note: ARNI example mentioned: Entresto (combination of Sacubitril and Valsartan).

This concludes the presentation on ACE inhibitors and ARBs.