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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Post-Myocardial Infarction (left ventricular dysfunction) * Diabetic Nephropathy (proteinuria) ## Adult Dosing * **Hypertension:** Initial doses vary by agent. Common starting doses include: * Benazepril: 5-10 mg once daily. Max: 40 mg/day. * Captopril: 12.5-25 mg twice daily. Max: 150 mg twice daily. * Enalapril: 5-10 mg once daily. Max: 40 mg/day. * Lisinopril: 10 mg once daily. Max: 40 mg/day. * Ramipril: 2.5-5 mg once daily. Max: 20 mg/day. * **Heart Failure:** Initial doses are typically lower than for hypertension. * Enalapril: 2.5-5 mg twice daily. Max: 20 mg twice daily. * Lisinopril: 5 mg once daily. Max: 35 mg/day. * Ramipril: 1.25-2.5 mg twice daily. Max: 10 mg twice daily. * **Post-Myocardial Infarction:** * Captopril: 6.25 mg three times daily. Max: 50 mg three times daily. * Enalapril: 2.5 mg twice daily, titrate up to 10 mg twice daily over several weeks. * Lisinopril: 5 mg once daily, titrate up to 10 mg once daily over several weeks. * **Diabetic Nephropathy:** * Benazepril: 10 mg once daily. Max: 20 mg/day. * Enalapril: 5-10 mg once daily. Max: 20 mg/day. * Lisinopril: 10 mg once daily. Max: 20 mg/day. * Ramipril: 5 mg once daily. Max: 10 mg/day. Dose titration should be individualized based on patient response and tolerability. ## Pediatric Dosing * **Hypertension:** Dosing is highly variable and often based on weight. Specific agents and dosages should be confirmed with pediatric guidelines. * Enalapril: 0.07 mg/kg/day once daily, max 0.61 mg/kg/day or 40 mg/day. * Captopril: 0.3 mg/kg/dose every 8 hours, max 6 mg/kg/day or 450 mg/day. * Lisinopril: 0.07 mg/kg/day once daily, max 0.61 mg/kg/day or 40 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce dose and/or increase dosing interval, especially in severe impairment (CrCl < 30 mL/min). Captopril and enalaprilat are renally excreted; others are renally eliminated as active metabolites. * **Hepatic Impairment:** Use with caution, especially prodrugs like enalapril and ramipril, as hepatic metabolism is required for activation. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes. * Concomitant use with sacubitril/valsartan within 36 hours of the last dose of an ACE inhibitor. * Pregnancy (teratogenic). * Known hypersensitivity. ## Adverse Effects * **Common:** Dry cough, hyperkalemia, dizziness, fatigue, hypotension. * **Less Common/Serious:** Angioedema, acute kidney injury, elevated liver enzymes, rash. ## Key Drug Interactions * **Potassium-Sparing Diuretics & Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs & COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Aliskiren:** Increased risk of hyperkalemia and hypotension; contraindicated in diabetes. * **ARBs:** Increased risk of hyperkalemia and renal dysfunction; generally avoid combination unless in specific heart failure protocols. * **Sacubitril/Valsartan:** Increased risk of angioedema. Do not initiate ACE inhibitors within 36 hours of stopping sacubitril/valsartan. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing risk of lithium toxicity. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During Therapy:** Serum creatinine, electrolytes (especially potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. Blood pressure. Monitor for cough and angioedema. ## Clinical Pearls * Cough is dose-dependent and typically resolves after discontinuation. * Angioedema is a medical emergency and requires immediate discontinuation. * Initiate at low doses and titrate slowly, especially in patients with heart failure, renal impairment, or those on diuretics. * Orthostatic hypotension can occur, particularly after the first dose or dose increase. * Avoid use in pregnancy. *** *Please verify this information with the most current prescribing information or relevant clinical guidelines.*