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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications primarily 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 (reduced ejection fraction) * Post-Myocardial Infarction (to improve survival) * Diabetic Nephropathy (in patients with type 1 diabetes and proteinuria) * Chronic Kidney Disease (in select patients) ## Adult Dosing Dosing varies significantly by specific agent, indication, and patient response. Titration is common. * **Benazepril:** Hypertension: 10-40 mg once daily. Heart Failure: 10 mg once daily, titrate up to 40 mg once daily. * **Captopril:** Hypertension: 25 mg twice daily, titrate up to 150 mg twice daily. Heart Failure: 6.25 mg three times daily, titrate up to 50 mg three times daily. Post-MI: 6.25 mg three times daily, titrate up to 12.5 mg three times daily. * **Enalapril:** Hypertension: 5 mg once daily, titrate up to 40 mg once daily. Heart Failure: 2.5 mg twice daily, titrate up to 10 mg twice daily. * **Fosinopril:** Hypertension: 10-40 mg once daily. Heart Failure: 5 mg once daily, titrate up to 40 mg once daily. * **Lisinopril:** Hypertension: 10 mg once daily, titrate up to 40 mg once daily. Heart Failure: 5 mg once daily, titrate up to 40 mg once daily. Post-MI: 5 mg once daily, titrate up to 40 mg once daily. * **Moexipril:** Hypertension: 7.5-30 mg once daily. * **Perindopril:** Hypertension: 2.5-10 mg once daily. Heart Failure: 2.5 mg once daily, titrate up to 10 mg once daily. * **Quinapril:** Hypertension: 10-80 mg once daily (divided BID if >40mg). Heart Failure: 5 mg once daily, titrate up to 20 mg twice daily. * **Ramipril:** Hypertension: 2.5-20 mg once daily. Heart Failure: 2.5 mg once daily, titrate up to 10 mg once daily. Post-MI: 2.5 mg twice daily, titrate up to 5 mg twice daily. * **Trandolapril:** Hypertension: 1-4 mg once daily. Heart Failure: 1 mg once daily, titrate up to 4 mg once daily. ## Pediatric Dosing Dosing in children is typically weight-based and requires careful monitoring. Specific protocols may vary. * **Benazepril:** Hypertension: 0.1-0.6 mg/kg/day divided once or twice daily (max 40 mg/day). * **Enalapril:** Hypertension: 0.07-0.1 mg/kg/day divided once or twice daily (max 40 mg/day). * **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/day once daily (max 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Dosage reduction is generally recommended, especially for drugs renally cleared (e.g., captopril, lisinopril, enalapril). Specific recommendations vary by agent and degree of renal impairment. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Caution is advised; dosage may need to be reduced for some agents (e.g., enalaprilat). ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue. * **Serious:** Angioedema (face, lips, tongue, throat, intestines), hyperkalemia, acute kidney injury, hypotension, rash, dysgeusia. ## Key Drug Interactions * **Diuretics (especially potassium-sparing):** Increased risk of hyperkalemia and hypotension. * **Potassium Supplements/Potassium-Containing Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment and hyperkalemia. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema; ACE inhibitors should not be used within 36 hours of switching to or initiating sacubitril/valsartan. ## Monitoring * Blood pressure (regularly). * Serum creatinine and blood urea nitrogen (BUN). * Serum potassium (especially with renal impairment, potassium supplements, or other potassium-retaining drugs). * Signs and symptoms of angioedema. * Renal function should be assessed before initiating and periodically thereafter. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. Switching to an angiotensin II receptor blocker (ARB) is often successful in patients who develop cough. * Start at low doses and titrate slowly, especially in volume-depleted patients, those with heart failure, or the elderly, to minimize the risk of profound hypotension. * First-dose hypotension can occur, particularly with diuretics or in patients with high renin levels. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Monitor for signs of hyperkalemia, especially in patients with impaired renal function or those on other medications that increase potassium. *** *This information is intended for clinical decision support and does not replace a thorough review of the current prescribing information for the specific agent being used.*