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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat hypertension and heart failure 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. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Left ventricular dysfunction post-myocardial infarction * Diabetic nephropathy (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor used, indication, and patient response. Common starting doses are often low and titrated upwards. * **Hypertension:** * Benazepril: Start 10 mg once daily, usual range 20-40 mg daily, max 80 mg daily. * Captopril: Start 12.5-25 mg twice daily, usual range 25-50 mg twice daily, max 150 mg twice daily. * Enalapril: Start 5-10 mg once daily, usual range 10-40 mg daily, max 40 mg daily. * Fosinopril: Start 10 mg once daily, usual range 20-40 mg daily, max 80 mg daily. * Lisinopril: Start 10 mg once daily, usual range 10-40 mg daily, max 80 mg daily. * Moexipril: Start 7.5 mg once daily, usual range 15-30 mg daily, max 30 mg daily. * Perindopril: Start 5 mg once daily, usual range 10-20 mg daily, max 20 mg daily. * Ramipril: Start 2.5 mg once daily, usual range 5-10 mg daily, max 20 mg daily. * Trandolapril: Start 1 mg once daily, usual range 2-4 mg daily, max 8 mg daily. * Quinapril: Start 10 mg once or twice daily, usual range 20-40 mg daily, max 80 mg daily. * **Heart Failure:** Dosing often starts lower and is titrated more slowly. Refer to specific guidelines for initiation and titration protocols (e.g., ACEI-CHF-10). * **Post-MI:** Typically started within 24 hours in hemodynamically stable patients. Common starting dose for Lisinopril is 5 mg daily, titrating to 10 mg daily. ## Pediatric Dosing * **Hypertension:** Dosing varies significantly by age and weight. * Enalapril: Neonates/Infants: 0.04-0.2 mg/kg/day divided every 12-24 hours. Children: 0.1-0.5 mg/kg/day divided every 12-24 hours, max 1 mg/kg/day or 40 mg/day. * Lisinopril: Children: 0.07-0.2 mg/kg/day once daily, max 40 mg/day. * **Other indications:** Consult specific pediatric guidelines. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in severe renal impairment (CrCl < 30 mL/min). Captopril and Fosinopril are often preferred in renal impairment as they are less dependent on renal excretion. * **Hepatic Impairment:** Generally no dose adjustment needed, but caution is advised. ## 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 (teratogenic risk, especially in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, fatigue, hyperkalemia, headache, rash. * **Serious:** Angioedema (including laryngeal edema), acute kidney injury, hyperkalemia, neutropenia/agranulocytosis (rare), hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, Potassium supplements, Salt substitutes containing potassium:** Increased risk of hyperkalemia. * **Diuretics (especially thiazides):** Increased risk of hypotension, particularly orthostatic hypotension. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid combination in patients with diabetes or renal impairment. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid routine combination. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. ## Monitoring * **Baseline:** Serum creatinine, BUN, electrolytes (especially potassium), blood pressure. * **During therapy:** * Renal function and electrolytes (especially potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Blood pressure regularly. * Monitor for signs/symptoms of angioedema. * If neutropenia is suspected (e.g., in patients with collagen vascular disease or renal impairment), monitor CBC. ## Clinical Pearls * Cough is a common side effect and often resolves upon discontinuation. Switching to an ARB may be an option if cough is bothersome. * First-dose hypotension is a risk, especially in volume-depleted patients or those on diuretics. Monitor closely after the first dose. * Angioedema is a rare but life-threatening side effect. Patients should be educated to stop the medication immediately and seek emergency care if swelling occurs. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Use with caution in patients with bilateral renal artery stenosis. *** **Disclaimer:** This information is intended for healthcare professionals and does not replace comprehensive drug information resources or clinical judgment. Always consult the most current prescribing information for the specific drug and indication before making treatment decisions.