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Wednesday, August 20, 2025

Angiotensin Converting Enzyme Inhibitors


Angiotensin-Converting Enzyme (ACE) inhibitors are one of the most widely prescribed classes of cardiovascular drugs. They form the cornerstone of therapy in hypertension, heart failure, post-myocardial infarction management, and diabetic nephropathy. Their mechanism of action is centered around blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing vascular resistance, blood pressure, and improving cardiac and renal outcomes.

Mechanism of Action

ACE inhibitors inhibit the angiotensin-converting enzyme, preventing the conversion of angiotensin I to angiotensin II. This leads to:

  • Reduced vasoconstriction: Decreases systemic vascular resistance and lowers blood pressure.

  • Reduced aldosterone secretion: Minimizes sodium and water retention, reducing preload.

  • Reduced sympathetic activity: Diminishes catecholamine release.

  • Increased bradykinin levels: Enhances vasodilation but may cause cough and angioedema.

The net effect is vasodilation, decreased blood pressure, reduced cardiac workload, and renoprotection in diabetes and chronic kidney disease.

Clinical Uses

ACE inhibitors are recommended as first-line therapy in several conditions:

  1. Hypertension – Effective as monotherapy or in combination with other agents. Particularly beneficial in patients with diabetes, heart failure, or chronic kidney disease.

  2. Heart Failure with Reduced Ejection Fraction (HFrEF) – Improves survival, reduces hospitalizations, and alleviates symptoms.

  3. Post-Myocardial Infarction (MI) – Decreases remodeling of the left ventricle, lowers risk of recurrent ischemia, and improves survival.

  4. Diabetic Nephropathy & Chronic Kidney Disease – Slows progression of renal disease by reducing intraglomerular pressure.

  5. Left Ventricular Dysfunction – Provides cardioprotection by reducing afterload and preventing remodeling.

Commonly Used ACE Inhibitors, Generic Names, and Doses

1. Captopril

  • Initial: 12.5–25 mg orally two or three times daily

  • Usual: 25–50 mg orally two or three times daily

  • Maximum: 450 mg/day

  • Notes: Short-acting; requires multiple daily dosing; often used in acute settings.

2. Enalapril

  • Initial: 5 mg once daily

  • Usual: 10–20 mg once or twice daily

  • Maximum: 40 mg/day

  • Notes: Widely prescribed; available as intravenous enalaprilat for hypertensive emergencies.

3. Lisinopril

  • Initial: 5–10 mg once daily

  • Usual: 10–40 mg once daily

  • Maximum: 80 mg/day (hypertension)

  • Notes: Long half-life; convenient once-daily dosing.

4. Ramipril

  • Initial: 2.5 mg once daily

  • Usual: 2.5–10 mg once or twice daily

  • Maximum: 20 mg/day

  • Notes: Strong evidence for post-MI and high-risk cardiovascular patients.

5. Perindopril

  • Initial: 2 mg once daily

  • Usual: 4–8 mg once daily

  • Maximum: 16 mg/day

  • Notes: Demonstrated mortality benefits in stable coronary artery disease.

6. Quinapril

  • Initial: 10–20 mg once daily

  • Usual: 20–40 mg once or twice daily

  • Maximum: 80 mg/day

7. Benazepril

  • Initial: 5–10 mg once daily

  • Usual: 20–40 mg once daily or divided doses

  • Maximum: 80 mg/day

8. Trandolapril

  • Initial: 1 mg once daily

  • Usual: 2–4 mg once daily

  • Maximum: 8 mg/day

9. Moexipril

  • Initial: 7.5 mg once daily

  • Usual: 7.5–30 mg once daily

  • Maximum: 30 mg/day

10. Fosinopril

  • Initial: 10 mg once daily

  • Usual: 20–40 mg once daily

  • Maximum: 80 mg/day

  • Notes: Dual excretion via kidney and liver; preferred in patients with renal dysfunction.

Contraindications

  • History of angioedema related to ACE inhibitor use

  • Bilateral renal artery stenosis or stenosis in a solitary kidney

  • Pregnancy (Category D) – teratogenic, may cause fetal renal damage

  • Severe hyperkalemia

  • Concomitant use with aliskiren in diabetic patients

Side Effects

  • Dry cough – due to increased bradykinin (10–20% of patients)

  • Hyperkalemia – especially in renal insufficiency or with potassium-sparing diuretics

  • Hypotension – marked fall in BP in volume-depleted patients

  • Angioedema – rare but potentially fatal; requires immediate discontinuation

  • Renal impairment – worsening kidney function in bilateral renal artery stenosis

  • Taste disturbances, rash, fatigue (less common)

Precautions

  • Monitor renal function and serum potassium before and during treatment.

  • Use with caution in patients with renal insufficiency, elderly, and volume-depleted states.

  • Gradual dose titration is recommended to minimize first-dose hypotension.

  • Avoid abrupt withdrawal in patients with heart failure.

Drug Interactions

  • Potassium-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene): Increased risk of hyperkalemia.

  • NSAIDs (ibuprofen, naproxen, diclofenac): May reduce antihypertensive effect and increase risk of renal impairment.

  • Diuretics (thiazides, loop diuretics): May enhance first-dose hypotension.

  • Lithium: ACE inhibitors reduce lithium clearance → risk of lithium toxicity.

  • Aliskiren: Contraindicated in diabetes and renal impairment due to increased risk of renal failure and hyperkalemia.

  • ARBs (Angiotensin Receptor Blockers): Combination increases risk of renal dysfunction and hyperkalemia, generally avoided.

Advantages of ACE Inhibitors

  • Proven mortality benefit in heart failure and post-MI patients.

  • Renoprotective effects in diabetes and proteinuric kidney disease.

  • Suitable for long-term use with a favorable safety profile.

Limitations

  • Not tolerated by all patients due to cough and angioedema.

  • Contraindicated in pregnancy and advanced kidney disease with hyperkalemia.

  • Sometimes requires switching to an Angiotensin Receptor Blocker (ARB) if intolerance develops.




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