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# ACE Inhibitors ## Overview ACE inhibitors (ACEIs) are a class of medications primarily used to manage cardiovascular disease. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival and reduce remodeling) * Diabetic nephropathy (proteinuria reduction) * Chronic kidney disease (proteinuria reduction) ## Adult Dosing Dosing varies significantly by agent. Doses are typically started low and titrated upwards based on patient response and tolerability. * **Benazepril:** Hypertension: 10-40 mg once daily. Heart failure: 5-20 mg twice daily. * **Captopril:** Hypertension: 25-150 mg twice daily. Heart failure: 6.25-12.5 mg three times daily. Post-MI: 6.25-12.5 mg three times daily. * **Enalapril:** Hypertension: 10-40 mg once daily. Heart failure: 2.5-20 mg twice daily. * **Fosinopril:** Hypertension: 20-40 mg once daily. Heart failure: 5-20 mg once daily. * **Lisinopril:** Hypertension: 10-40 mg once daily. Heart failure: 2.5-35 mg once daily. Post-MI: 5-35 mg once daily. * **Moexipril:** Hypertension: 7.5-30 mg once daily. * **Perindopril:** Hypertension: 2.5-10 mg once daily. Heart failure: 2.5-10 mg once daily. Post-MI: 2.5-10 mg once daily. * **Quinapril:** Hypertension: 10-80 mg once daily or divided twice daily. Heart failure: 5-40 mg twice daily. * **Ramipril:** Hypertension: 2.5-20 mg once daily. Heart failure: 2.5-10 mg once daily. Post-MI: 5-10 mg once daily. * **Trandolapril:** Hypertension: 1-4 mg once daily. Heart failure: 0.5-2 mg once daily. Maximum doses are agent-specific and should be guided by clinical response. ## Pediatric Dosing * **Hypertension:** Dosing is highly variable. * **Captopril:** 0.3-0.5 mg/kg/dose every 8-12 hours. Max: 2 mg/kg/day or 50 mg/day. * **Enalapril:** 0.07-0.1 mg/kg/dose every 12-24 hours. Max: 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07-0.2 mg/kg/day once daily. Max: 40 mg/day. * **Ramipril:** 0.05-0.1 mg/kg/day once daily. Max: 10 mg/day. * **Other indications:** Specific pediatric dosing for heart failure or kidney disease is less established and may require specialist consultation. ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary, particularly for renally eliminated ACEIs (e.g., captopril, lisinopril). Specific guidelines vary by agent and degree of renal impairment. * **Hepatic Impairment:** Generally, no dose adjustment is required for most ACEIs, though caution may be warranted with agents that undergo significant hepatic metabolism. ## Contraindications * History of angioedema related to ACEI therapy. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (especially second and third trimesters, due to risk of fetal injury or death). * Known hypersensitivity to the specific ACEI. ## Adverse Effects * **Common:** Dry cough, dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (facial, lip, tongue, throat swelling; potentially life-threatening), acute kidney injury (especially in susceptible individuals), hypotension, hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction, especially in patients with volume depletion. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use in patients with diabetes or renal impairment. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. * **Lithium:** ACEIs can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly assess for hypotension and adequate blood pressure control. * **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and with dose changes. * **Electrolytes:** Monitor serum potassium, especially in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics. * **Angioedema:** Educate patients to report any signs/symptoms immediately. ## Clinical Pearls * The characteristic dry cough is dose-dependent and usually resolves upon discontinuation. If persistent and bothersome, consider switching to an ARB. * Initiate at a low dose and titrate slowly, particularly in elderly patients, those with volume depletion, or significant renal impairment. * ACEIs are generally well-tolerated and are cornerstone medications for many cardiovascular and renal conditions. * Discontinue immediately if angioedema occurs. * Avoid use in pregnancy. *** **Disclaimer:** This information is intended for clinical use and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before making any treatment decisions.