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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs primarily used to treat cardiovascular conditions like hypertension, heart failure, and myocardial infarction. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thus leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Congestive heart failure (CHF) * Left ventricular dysfunction post-myocardial infarction (MI) * Diabetic nephropathy (certain agents) * Proteinuric chronic kidney disease (certain agents) ## Adult Dosing Dosing varies significantly by agent and indication. Doses should be titrated upwards based on patient response and tolerability. * **Hypertension:** * Benazepril: Start 10 mg PO once daily, titrate to 20-40 mg/day. Max 80 mg/day. * Captopril: Start 25 mg PO BID, titrate to 50 mg TID. Max 150 mg TID. * Enalapril: Start 5 mg PO once daily, titrate to 10-40 mg/day. Max 40 mg/day. * Fosinopril: Start 10 mg PO once daily, titrate to 20-40 mg/day. Max 80 mg/day. * Lisinopril: Start 10 mg PO once daily, titrate to 20-40 mg/day. Max 80 mg/day. * Moexipril: Start 7.5 mg PO once daily, titrate to 15 mg/day. Max 30 mg/day. * Perindopril: Start 2.5-5 mg PO once daily, titrate to 10 mg/day. Max 10 mg/day. * Ramipril: Start 2.5 mg PO once daily, titrate to 10 mg/day. Max 10 mg/day. * Trandolapril: Start 1 mg PO once daily, titrate to 2-4 mg/day. Max 8 mg/day. * **Congestive Heart Failure (CHF):** * Enalapril: Start 2.5 mg PO BID, titrate to 10-20 mg BID. Max 20 mg BID. * Lisinopril: Start 5 mg PO once daily, titrate to 10-20 mg once daily. Max 40 mg/day. * Captopril: Start 6.25 mg PO TID, titrate to 50 mg TID. Max 150 mg TID. * Ramipril: Start 1.25 mg PO once daily, titrate to 5 mg BID. Max 10 mg BID. * **Post-MI:** * Captopril: Start 6.25 mg PO TID, titrate to 50 mg TID. Start within 24 hours of MI. Max 150 mg TID. * Enalapril: Start 2.5 mg PO BID, titrate to 5 mg BID. Start within 24 hours of MI. Max 10 mg BID. * Lisinopril: Start 5 mg PO once daily, titrate to 10 mg once daily. Start within 24 hours of MI. Max 10 mg/day. * Ramipril: Start 1.25 mg PO once daily, titrate to 5 mg BID. Start within 24 hours of MI. Max 10 mg BID. * **Diabetic Nephropathy/Proteinuric CKD:** Dosing is highly individualized and dependent on the specific ACE inhibitor and patient characteristics. Generally start low and titrate as tolerated to achieve proteinuria reduction. ## Pediatric Dosing Dosing in children is less established and should be guided by expert consultation and specific product labeling. Doses are often weight-based. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/dose PO BID. Max 0.61 mg/kg/day (or 40 mg/day). * Lisinopril: 0.07-0.2 mg/kg/dose PO once daily. Max 20 mg/day. * Captopril: 0.3 mg/kg/dose PO TID. Max 6 mg/kg/day (or 150 mg/day). ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate slowly. Specific dose adjustments depend on the agent and creatinine clearance. Monitor potassium closely. * **Hepatic Impairment:** Caution is advised, as hepatic metabolism can be affected. Start with lower doses. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters; Category C in 1st trimester). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (rare but life-threatening), acute kidney injury (especially in patients with bilateral renal artery stenosis), hypotension, rash, liver enzyme elevations. ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride), potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in elderly or volume-depleted patients. * **Diuretics (especially thiazides):** Increased risk of hypotension, particularly after the first dose of ACE inhibitor. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., everolimus, sirolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. * **Aliskiren:** Increased risk of hyperkalemia and hypotension; contraindicated in patients with diabetes or renal impairment. ## Monitoring * **Blood Pressure:** Regularly monitor for symptomatic hypotension. * **Renal Function:** Baseline and periodic monitoring of serum creatinine and BUN. * **Serum Potassium:** Baseline and periodic monitoring, especially in patients with renal impairment or on potassium-sparing agents. * **Angioedema:** Educate patients on signs and symptoms and to seek immediate medical attention. ## Clinical Pearls * Cough is a common, dose-limiting side effect, occurring in up to 20% of patients. If cough is bothersome, consider switching to an ARB. * Start low and titrate slowly, especially in elderly patients, those with heart failure, or renal impairment. * Administer with or without food, but consistency is advised. * Discontinue immediately if angioedema occurs. * Avoid use in pregnancy due to potential fetal harm. *** *This information is intended for healthcare professionals and does not replace comprehensive drug prescribing information. Always consult the most current product labeling and relevant clinical guidelines for complete and up-to-date information before prescribing.*