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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 (reduced ejection fraction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (in patients with type 1 diabetes and proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is usually performed every 1-4 weeks. * **Hypertension:** * Benazepril: Start at 10 mg once daily, titrate up to 40 mg/day. * Captopril: Start at 25 mg twice daily, titrate up to 150 mg twice daily. * Enalapril: Start at 5 mg once daily, titrate up to 40 mg/day. * Fosinopril: Start at 10 mg once daily, titrate up to 40 mg/day. * Lisinopril: Start at 10 mg once daily, titrate up to 40 mg/day. * Moexipril: Start at 7.5 mg once daily, titrate up to 30 mg/day. * Perindopril: Start at 2.5-5 mg once daily, titrate up to 10 mg/day. * Quinapril: Start at 10 mg once or twice daily, titrate up to 80 mg/day. * Ramipril: Start at 2.5-5 mg once daily, titrate up to 10 mg/day. * Trandolapril: Start at 1 mg once daily, titrate up to 4 mg/day. * **Heart Failure:** * Benazepril: Start at 10 mg once daily, titrate up to 40 mg/day. * Captopril: Start at 6.25 mg three times daily, titrate up to 50 mg three times daily. * Enalapril: Start at 2.5 mg twice daily, titrate up to 10 mg twice daily. * Lisinopril: Start at 5 mg once daily, titrate up to 40 mg/day. * Ramipril: Start at 1.25-2.5 mg twice daily, titrate up to 10 mg/day. * **Post-Myocardial Infarction:** * Lisinopril: Start 5 mg within 24 hours of MI, then 5 mg daily for 6 days, then 10 mg daily. * Ramipril: Start 1.25 mg once daily, titrate up to 5 mg twice daily. * **Diabetic Nephropathy (Type 1, with proteinuria):** * Lisinopril: Start at 10 mg once daily, may increase to 20 mg once daily. ## Pediatric Dosing Established pediatric dosing varies by agent and indication. Consult specific pediatric guidelines for precise dosing. * **Hypertension:** * Enalapril: 200 mcg/kg once daily, may increase to 400 mcg/kg/day. Maximum 40 mg/day. * Lisinopril: 7-10 years: 2.5 mg once daily; 11-16 years: 5 mg once daily. Maximum 20 mg/day. * Ramipril: 2.5 mg once daily for children > 50 kg, or 0.05 mg/kg/day for children < 50 kg. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Captopril and Moexipril require more significant dose adjustments. Monitor potassium and renal function. * **Hepatic Impairment:** Generally no dose adjustment needed for most, but use with caution. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Less Common/Serious:** Angioedema (potentially life-threatening), acute kidney injury, rash, taste disturbances, neutropenia, elevated liver enzymes. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs, spironolactone:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May decrease antihypertensive effect and increase risk of renal impairment. * **Diuretics (thiazide, loop):** Increased risk of symptomatic hypotension, especially after the first dose. * **Lithium:** Increased lithium levels and toxicity. * **Mammalian target of rapamycin (mTOR) inhibitors (e.g., sirolimus, everolimus), racecadotril, neprilysin inhibitors:** Increased risk of angioedema. ## Monitoring * Blood pressure (before and after initiation/titration). * Serum potassium and creatinine (baseline, 1-2 weeks after initiation/titration, then periodically). * Renal function. * Signs and symptoms of angioedema or hypersensitivity reactions. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an ARB. * Risk of first-dose hypotension is higher in patients who are volume-depleted, have heart failure, or are taking diuretics. Consider a lower starting dose and careful monitoring. * Angioedema can occur at any time during therapy and is a medical emergency. * ACE inhibitors are generally considered renoprotective in diabetic patients with proteinuria. *** This information is intended for healthcare professionals and does not replace current prescribing information or clinical judgment. Always verify the most up-to-date drug information with official product labeling and relevant guidelines.