Medicine & USMLE

ACE Inhibitors

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Renal Drugs (New)
  1. Aliskiren
  2. Mannitol
  3. Thiazide Diuretics
  4. ACE Inhibitors
  5. ARBs

Summary

ACE inhibitors are medications that end in -pril, such as captopril, lisinopril, enalapril, ramipril, and benazepril.

They work by inhibiting angiotensin-converting enzyme, leading to decreased levels of angiotensin II. This blocks the constriction of the efferent arterioles of the glomerulus, which can decrease intraglomerular pressure and reduce the glomerular filtration rate.  This can help block any thickening of the glomerular basement membrane. ACE inhibitors can lead to an increase in renin levels. They also prevent the breakdown of bradykinin.

Clinically, ACE inhibitors are used to treat heart failure, where they have been proven to reduce mortality. They are used to treat hypertension and can help prevent unfavorable heart remodeling in chronic hypertension. They may also be used to treat proteinuria, renal failure, and diabetic nephropathy.

Side effects of ACE inhibitors include hypotension, cough, angioedema, hyperkalemia, and increased creatinine levels. They are contraindicated in patients with C1 esterase inhibitor deficiency and should be used with caution in bilateral renal artery stenosis. ACE inhibitors are also teratogenic and can cause fetal renal malformations.

Key Points

  • Angiotensin Converting Enzyme (ACE) inhibitors
    • Drug Names
      • -pril ending
        • Captopril
        • Lisinopril
        • Enalapril
        • Ramipril
        • Benazepril
    • Mechanisms
      • Inhibits ACE
        • ↓ Angiotensin II (AT-II) levels
      • Prevents constriction of efferent arterioles of glomeruli
        • ↓ GFR
        • Decreases intraglomerular pressure
        • Blocks thickening of glomerular basement membrane
      • ↑ Plasma Renin
        • Due to loss of negative feedback
      • Prevents breakdown of bradykinin
        • Can lead to side effects of cough and angioedema
    • Clinical Use
      • Treats hypertension
        • Prevents unfavorable cardiac remodeling (in chronic HTN)
        • ACEI are still first-line, since ACEI are proven to reduce mortality while ARB do not
        • Used in hypertension and heart failure due to left ventricular systolic dysfunction
      • Treats heart failure
        • Reduces mortality
          • Demonstrated to reduce mortality in patients over time
      • Treats chronic kidney disease (renal failure)
      • Treats diabetic nephropathy (diabetic kidney disease)
        • Decreases rate of glomerular basement membrane thickening, prevents progression to chronic kidney disease
      • Treats proteinuria
    • Side Effects
      • Cough
        • Dry cough originates from accumulation of bradykinin
      • Angioedema
        • Potentially life-threatening complication of bradykinin accumulation
        • Presents as rapid-onset swelling of lips and tongue; may close the airway
        • Contraindicated in C1 esterase inhibitor deficiency
          • C1 esterase inhibitor deficiency also causes increase in bradykinin, which can compound with ACE inhibitors to doubly cause angioedema
      • Hypotension
      • Hyperkalemia
        • Decreased angiotensin II signaling causes reduction in aldosterone, which reduces potassium retention from urine
      • Increase creatinine
        • Due to decrease in GFR
      • Teratogen
        • May cause fetal kidney malformations
      • Use with Caution in bilateral renal artery stenosis
        • In bilateral renal artery stenosis, angiotensin II is necessary to maintain GFR. Inhibiting angiotensin II’s effects can lead to rapid renal failure.