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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications used to treat hypertension, heart failure, and certain kidney diseases. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (left ventricular dysfunction) * Diabetic nephropathy * Proteinuric chronic kidney disease ## Adult Dosing Dosing is highly variable depending on the specific ACE inhibitor and indication. Titration is typically required. * **Hypertension:** Common starting doses include: * Lisinopril: 10 mg orally once daily * Enalapril: 5 mg orally once or twice daily * Ramipril: 2.5 mg orally once daily * Benazepril: 10 mg orally once daily * Maximum doses vary but often range from 40 mg (lisinopril, enalapril) to 20 mg (ramipril, benazepril) daily. * **Heart Failure:** * Lisinopril: Start at 5 mg orally once daily, titrate up to 40 mg once daily. * Enalapril: Start at 2.5 mg orally twice daily, titrate up to 10 mg twice daily. * Ramipril: Start at 1.25 mg orally once daily, titrate up to 10 mg once daily. * **Post-Myocardial Infarction:** * Lisinopril: Start at 5 mg orally once daily, with additional doses of 5 mg and 10 mg after 24 hours and then continue at 10 mg once daily. * Ramipril: Start at 2.5 mg orally twice daily, increase to 5 mg twice daily after 1 week, and then to a target of 10 mg twice daily. * **Diabetic Nephropathy:** Dosing is often guided by blood pressure response and ACE inhibitor specific guidelines. ## Pediatric Dosing ACE inhibitors are approved for pediatric hypertension. Dosing is weight-based and varies by agent. * **Enalapril:** 0.07 to 0.1 mg/kg/dose orally every 24 hours. Maximum 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07 to 0.2 mg/kg/dose orally every 24 hours. Maximum 40 mg/day. * **Captopril:** 0.3 mg/kg/dose orally every 8 hours. Maximum 4.5 mg/kg/day or 150 mg/day. ## Dose Adjustments * **Renal Impairment:** Initial doses should be reduced in patients with significantly impaired renal function (e.g., creatinine clearance < 30 mL/min). Dose titration should be more gradual. Specific recommendations vary by drug and renal function. * **Hepatic Impairment:** No specific dose adjustments are usually recommended, but caution is advised. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (contraindicated during the second and third trimesters). ## Adverse Effects * **Dry Cough:** Common, often dose-limiting. * **Hypotension:** Especially with the first dose or in volume-depleted patients. * **Hyperkalemia:** Risk increased in renal impairment, with potassium supplements, or potassium-sparing diuretics. * **Angioedema:** Rare but life-threatening. More common in Black patients. * **Renal dysfunction:** Can occur, especially in patients with pre-existing renal artery stenosis. * **Dizziness, fatigue, headache.** * **Rash.** ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) and Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce the antihypertensive effect and increase the risk of renal dysfunction. * **Diuretics:** Additive hypotensive effect. May require dose reduction of ACE inhibitor. * **Lithium:** ACE inhibitors may reduce lithium clearance, leading to increased lithium levels and toxicity. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in patients with diabetes. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Generally avoided in combination. ## Monitoring * **Blood Pressure:** Regular monitoring for efficacy and to assess for hypotension. * **Renal Function (Serum Creatinine and BUN):** Baseline and periodically, especially in patients with renal impairment or risk factors. * **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment, on potassium supplements, or potassium-sparing diuretics. * **Angioedema:** Patients should be educated to report any signs of angioedema immediately. ## Clinical Pearls * Initiate at a low dose and titrate slowly to minimize hypotension and cough. * Discontinue immediately if angioedema occurs and do not re-challenge. * Patients of African descent may have a less pronounced blood pressure response to ACE inhibitors compared to other antihypertensives; consider a diuretic or calcium channel blocker as first-line therapy. * ACE inhibitors are renoprotective in patients with diabetic nephropathy and proteinuria. * Consider switching to an ARB if cough is persistent and bothersome, although cross-reactivity with angioedema can occur. *** **Disclaimer:** This information is intended for clinical use and does not replace the most current prescribing information or professional medical advice. Always verify drug information with authoritative sources and consider individual patient factors.