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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat hypertension and heart failure. 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) * Myocardial infarction (post-MI, to reduce mortality and reinfarction) * Diabetic nephropathy ## Adult Dosing Dosing varies significantly by agent. Titration is typically required based on patient response and tolerance. * **Benazepril:** Start at 5-10 mg once daily, titrate to 20-40 mg daily in 1-2 divided doses. * **Captopril:** Start at 25 mg twice daily, titrate to 50 mg three times daily. Maximum dose: 150 mg three times daily. * **Enalapril:** Start at 2.5-5 mg once or twice daily, titrate to 10-20 mg once or twice daily. Maximum dose: 40 mg daily. * **Fosinopril:** Start at 10 mg once daily, titrate to 20-40 mg once daily. Maximum dose: 80 mg daily. * **Lisinopril:** Start at 5-10 mg once daily, titrate to 20-40 mg once daily. Maximum dose: 80 mg daily. * **Moexipril:** Start at 7.5 mg once daily, titrate to 15 mg twice daily. Maximum dose: 30 mg daily. * **Perindopril:** Start at 2.5-5 mg once daily, titrate to 10 mg once daily. * **Quinapril:** Start at 5-10 mg twice daily, titrate to 20-40 mg twice daily. Maximum dose: 80 mg daily. * **Ramipril:** Start at 2.5 mg once daily, titrate to 5-10 mg once daily. * **Trandolapril:** Start at 0.5-1 mg once daily, titrate to 2-4 mg once daily. ## Pediatric Dosing ACE inhibitors are not typically first-line agents in pediatric hypertension due to less extensive data. Dosing is often weight-based and requires careful monitoring. * **Enalapril:** 0.07-0.1 mg/kg/dose orally once or twice daily. Maximum: 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07-0.2 mg/kg/dose orally once daily. Maximum: 40 mg/day. * **Ramipril:** Data is limited. ## Dose Adjustments * **Renal Impairment:** Dose reduction may be necessary, especially in severe renal impairment. Start with lower doses and titrate cautiously. In patients on dialysis, doses may be given after dialysis. * **Hepatic Impairment:** Caution is advised. Captopril and enalapril may require dose reduction. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (contraindicated; can cause fetal injury or death). ## Adverse Effects * **Common:** Dry cough, dizziness, hypotension, headache, fatigue, hyperkalemia. * **Less Common/Serious:** Angioedema (facial, lingual, laryngeal, intestinal), acute kidney injury, neutropenia, agranulocytosis, hepatotoxicity, Stevens-Johnson syndrome. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May diminish antihypertensive effect and increase risk of renal dysfunction, particularly in patients with compromised renal function. * **Diuretics (especially loop or thiazide):** Increased risk of symptomatic hypotension, particularly after the first dose of the ACE inhibitor. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. * **Racecadotril:** Increased risk of angioedema. * **Neprilysin inhibitors (e.g., sacubitril):** Increased risk of angioedema. Avoid concomitant use; if switching from ACE inhibitor to neprilysin inhibitor, allow at least 36 hours after the last dose of ACE inhibitor. ## Monitoring * Blood pressure (seated, standing). * Serum potassium. * Renal function (serum creatinine, BUN). * Baseline and periodic complete blood count (CBC) with differential, especially in patients at risk for neutropenia. * Signs and symptoms of angioedema. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB). * Initiate therapy with low doses and titrate slowly, especially in patients with volume depletion, hyponatremia, or renal impairment, to minimize the risk of profound hypotension. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * First-dose hypotension can occur, particularly in patients taking diuretics. Consider withholding diuretics or giving a lower first dose of the ACE inhibitor. * Angioedema is a medical emergency and can be fatal. Discontinue ACE inhibitor immediately and do not rechallenge. * Avoid in pregnancy due to risk of fetal harm. *** *This information is intended for educational purposes and does not substitute for professional medical advice. Always consult with a qualified healthcare provider to determine the best course of treatment for your specific condition. Prescribing information for individual agents may vary. Always verify current prescribing information.*