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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (in patients with proteinuria) * Chronic kidney disease (in patients with proteinuria) ## Adult Dosing Dosing varies significantly by specific ACE inhibitor, indication, and patient response. Titration is typically guided by blood pressure response and tolerability. * **Hypertension:** Initial doses are generally low, with titration to a maximum dose based on the specific agent and blood pressure goal. Examples: * Lisinopril: 10 mg once daily, titrate up to 40 mg once daily. * Enalapril: 5 mg once or twice daily, titrate up to 40 mg once daily (or 20 mg twice daily). * Ramipril: 2.5 mg once daily, titrate up to 10 mg once daily. * **Heart Failure:** Dosing often starts lower and is titrated more slowly than for hypertension. * Enalapril: 2.5 mg twice daily, titrate up to 10-20 mg twice daily. * Lisinopril: 5 mg once daily, titrate up to 40 mg once daily. * Captopril: 6.25 mg three times daily, titrate up to 50 mg three times daily. * **Post-MI:** Typically initiated within 24 hours of MI in patients without contraindications. * Captopril: 6.25 mg three times daily, increasing to 12.5 mg three times daily, then 25 mg three times daily. * Ramipril: 2.5 mg twice daily, increasing to 5 mg twice daily, then 10 mg twice daily. ## Pediatric Dosing ACE inhibitor dosing in pediatric populations is less standardized and often based on weight. Specific recommendations vary by agent and indication. * **Hypertension:** * Enalapril: 0.1 mg/kg/dose once daily, may titrate up to 0.5 mg/kg/day divided BID. Maximum dose varies by agent. * Lisinopril: 0.07 mg/kg/dose once daily, may titrate up to 0.6 mg/kg/day (maximum 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate slowly. Monitoring of renal function and potassium is crucial. Specific recommendations vary by agent and degree of renal impairment (e.g., CrCl <30 mL/min). * **Hepatic Impairment:** Use with caution. ## Contraindications * History of angioedema related to ACE inhibitor therapy * Concomitant use with aliskiren in patients with diabetes * Pregnancy (especially second and third trimesters) * Known hypersensitivity to ACE inhibitors ## Adverse Effects * **Angioedema:** Rare but potentially life-threatening swelling of the face, lips, tongue, throat, or intestines. * **Cough:** Dry, persistent cough (most common adverse effect). * **Hyperkalemia:** Increased serum potassium levels. * **Hypotension:** Especially with the first dose or in volume-depleted patients. * **Renal dysfunction:** Can cause acute kidney injury, particularly in patients with bilateral renal artery stenosis or severe heart failure. * Dizziness, fatigue, headache, rash. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment. * **Lithium:** Increased lithium levels and risk of toxicity. * **Diuretics:** Increased risk of symptomatic hypotension. * **mTOR inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. ## Monitoring * Blood pressure * Serum potassium and creatinine (renal function) * Signs and symptoms of angioedema and cough ## Clinical Pearls * Initiate at low doses and titrate slowly, especially in elderly patients, those with heart failure, or renal impairment. * Consider alternatives for patients who develop a persistent cough. * Angioedema is a medical emergency; discontinue ACE inhibitor immediately and manage airway. * Monitor renal function and potassium closely, especially when used with other medications that affect the renin-angiotensin-aldosterone system or potassium levels. * Discontinue ACE inhibitors at least 3 days before starting an ARB or if pregnancy is detected. *** *This information is intended for healthcare professionals. Please consult the most current prescribing information and relevant clinical guidelines for complete details and to verify dosage and safety information before use.*