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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) 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 (NYHA Class II-IV) * Left ventricular dysfunction post-myocardial infarction * Diabetic nephropathy (in patients with type 1 diabetes and proteinuria) ## Adult Dosing Dosing varies significantly by specific ACE inhibitor. General starting doses are typically low and titrated upwards based on patient response and tolerability. Maximum daily doses are also specific to each agent. * **Hypertension:** Starting doses commonly range from captopril 12.5-25 mg BID, enalapril 2.5-5 mg daily, lisinopril 5-10 mg daily, ramipril 2.5 mg daily. Titration to effective blood pressure control is typical. * **Heart Failure:** Starting doses often are lower than for hypertension. For example, enalapril 2.5-5 mg BID, lisinopril 2.5-5 mg daily, ramipril 1.25-2.5 mg daily. Titration is guided by symptoms and tolerability. * **Post-MI:** Enalapril 2.5-5 mg BID, lisinopril 5 mg daily, ramipril 1.25-2.5 mg BID. * **Diabetic Nephropathy:** Captopril 25 mg TID or enalapril 5-10 mg daily. ## Pediatric Dosing ACE inhibitors are generally not recommended as first-line therapy for pediatric hypertension unless specific compelling indications exist (e.g., certain renal diseases, specific congenital heart disease). Dosing is weight-based and requires careful monitoring. * **Hypertension:** * Enalapril: 0.08 mg/kg/day divided BID, max 0.59 mg/kg/day or 40 mg/day. * Lisinopril: 0.07 mg/kg/day once daily, max 20 mg/day. * Captopril: 0.3 mg/kg/day divided TID, max 6 mg/kg/day or 450 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce dose and/or increase dosing interval. Initial doses should be lower in patients with moderate to severe renal impairment (e.g., CrCl < 30 mL/min). * **Hepatic Impairment:** Use with caution, may require dose reduction. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters, Category X in 1st trimester). ## Adverse Effects * **Common:** Dry cough (up to 20%), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Less Common/Serious:** Angioedema (can be fatal), acute kidney injury, rash, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs, NSAIDs:** Increased risk of hyperkalemia. * **Diuretics (especially thiazides):** Increased risk of hypotension, particularly with the first dose. * **Lithium:** Increased lithium levels and risk of toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., saxagliptin, linagliptin):** Increased risk of angioedema. ## Monitoring * Blood pressure (before and after initiation/titration). * Serum creatinine and potassium (within 1-2 weeks of initiation or dose increase, and periodically thereafter). * Renal function in patients with underlying renal disease or at risk. * Signs and symptoms of angioedema or hypersensitivity. * WBC count (rarely, if risk factors for neutropenia exist). ## Clinical Pearls * The characteristic dry cough is typically reversible upon discontinuation. * Angioedema is a medical emergency and requires immediate discontinuation and management. * Initiate at low doses in elderly patients, those with volume depletion, or renal impairment. * ACE inhibitors are generally preferred over ARBs in patients with heart failure and post-MI unless angioedema or significant cough occurs. * Avoid use in pregnancy. *** *This information is intended for healthcare professionals. Please verify current prescribing information for complete details before making clinical decisions.*