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# ACE Inhibitors ## Overview ACE inhibitors (ACEIs) are a class of medications that block the action of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. This results in a decrease in blood pressure. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (for selected patients) * Diabetic nephropathy (in patients with type 1 diabetes and hypertension or proteinuria) * Chronic kidney disease (in patients with hypertension or proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Typical starting doses and maximum doses are listed below for common agents. Titration is guided by blood pressure response and tolerability. * **Benazepril:** Start 10 mg once daily. Max 40 mg once daily. * **Captopril:** Start 25 mg twice daily. Max 150 mg three times daily. (Requires more frequent dosing) * **Enalapril:** Start 5 mg once daily. Max 40 mg once daily. (Can be given IV: 1.25 mg every 6 hours) * **Fosinopril:** Start 10 mg once daily. Max 80 mg once daily. * **Lisinopril:** Start 10 mg once daily. Max 40 mg once daily. * **Moexipril:** Start 7.5 mg once daily. Max 30 mg once daily. * **Perindopril:** Start 2.5-5 mg once daily. Max 10 mg once daily. * **Quinapril:** Start 10 mg once daily or twice daily. Max 80 mg once daily or twice daily. * **Ramipril:** Start 2.5 mg once daily. Max 10 mg once daily. * **Trandolapril:** Start 1 mg once daily. Max 8 mg once daily. For heart failure, ACEIs are often initiated at lower doses and titrated more slowly to a target dose or the maximum tolerated dose. ## Pediatric Dosing ACE inhibitors are approved for hypertension in pediatric patients. Dosing is highly variable and should be based on body weight. * **Enalapril:** 0.07 mg/kg/day to 0.5 mg/kg/day divided once or twice daily. Maximum dose varies by indication and age. * **Lisinopril:** 0.07 mg/kg/day to 0.21 mg/kg/day once daily. Maximum dose 40 mg/day. Refer to specific pediatric guidelines for precise dosing based on age and weight. ## Dose Adjustments * **Renal Impairment:** Initial doses should be reduced in patients with significant renal impairment (creatinine clearance < 30 mL/min). Dose titration should be cautious. * **Hepatic Impairment:** Captopril and enalapril may require dose reduction. ## Contraindications * History of angioedema related to prior ACEI treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (Category D in 2nd and 3rd trimesters; Category C in 1st trimester). * Known hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Less Common/Serious:** Angioedema (can be life-threatening), hypotension, renal dysfunction (especially in patients with bilateral renal artery stenosis or severe heart failure), rash, dysgeusia, neutropenia, agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics & Potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Lithium:** ACEIs can increase serum lithium levels, leading to toxicity. * **Diuretics (thiazide/loop):** Additive hypotensive effect; increased risk of symptomatic hypotension, especially with first-dose therapy. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. Do not use ACEIs concurrently; initiate sacubitril/valsartan at least 36 hours after the last dose of an ACEI. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction; contraindicated in patients with diabetes. ## Monitoring * **Blood Pressure:** Regularly monitor before and during treatment. * **Serum Potassium:** Monitor periodically, especially in patients with renal impairment or those taking potassium supplements/sparing diuretics. * **Renal Function (BUN, Creatinine):** Monitor periodically, especially in patients with pre-existing renal disease or risk factors. * **Signs of Angioedema:** Educate patients on symptoms and to seek immediate medical attention. * **Complete Blood Count (CBC):** Consider in patients at risk for neutropenia (e.g., those with collagen vascular disease). ## Clinical Pearls * Cough is a common side effect, often dose-limiting, and usually resolves after discontinuation. Consider switching to an angiotensin II receptor blocker (ARB). * First-dose hypotension can occur, particularly in volume-depleted patients or those on diuretics. Start at a lower dose, especially for heart failure patients, and monitor closely after initiation. * ACEIs are generally safe in pregnancy up to the first trimester but are contraindicated in the second and third trimesters due to the risk of fetal harm. * Discontinue ACEIs immediately if angioedema occurs. * Patients with bilateral renal artery stenosis or severe heart failure are at increased risk of renal deterioration. *** **Disclaimer:** This information is for educational purposes only and does not substitute for professional medical advice. Always consult current prescribing information, drug monographs, and institutional protocols for complete and up-to-date details before making any treatment decisions.