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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used for hypertension and heart failure. They work 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, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (MI) * Diabetic nephropathy * Proteinuric chronic kidney disease ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Starting doses are typically low and titrated upwards. * **Hypertension:** * Benazepril: Start 10 mg once daily, max 40 mg/day. * Captopril: Start 12.5-25 mg twice daily, max 150 mg twice daily. * Enalapril: Start 5-10 mg once daily, max 40 mg/day. * Fosinopril: Start 10 mg once daily, max 80 mg/day. * Lisinopril: Start 10 mg once daily, max 40 mg/day. * Moexipril: Start 7.5 mg once daily, max 30 mg/day. * Perindopril: Start 2.5-5 mg once daily, max 10 mg/day. * Quinapril: Start 10 mg once or twice daily, max 80 mg/day. * Ramipril: Start 2.5-5 mg once daily, max 10 mg/day. * Trandolapril: Start 1 mg once daily, max 8 mg/day. * **Heart Failure:** * Enalapril: Start 2.5 mg twice daily, titrate up to target dose of 10 mg twice daily. Max 40 mg/day. * Lisinopril: Start 5 mg once daily, titrate up to target dose of 10-20 mg once daily. Max 40 mg/day. * Ramipril: Start 1.25-2.5 mg twice daily, titrate up to target dose of 5 mg twice daily. Max 10 mg/day. * Captopril: Start 6.25 mg three times daily, titrate up to target dose of 50 mg three times daily. * Starting doses for other ACE inhibitors in heart failure are generally lower than for hypertension and titration is cautious. * **Post-MI and Diabetic Nephropathy:** Dosing typically follows guidelines for hypertension and heart failure, aiming for target doses where tolerated. ## Pediatric Dosing ACE inhibitors are used in pediatric patients, particularly for hypertension and heart failure. Dosing is often based on weight and requires careful titration. * **Hypertension:** * Enalapril: 0.07-0.2 mg/kg/day in 1-2 divided doses. Max 0.6 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/day once daily. Max 0.6 mg/kg/day or 40 mg/day. * Captopril: 0.3 mg/kg/dose every 8-12 hours. Max 3 mg/kg/day or 150 mg/day. * **Heart Failure:** Dosing is typically initiated at lower doses than for hypertension and titrated carefully. Specific pediatric guidelines should be consulted. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in severe renal impairment. Consult specific drug monographs for recommended adjustments. Monitor potassium closely. * **Hepatic Impairment:** Captopril and enalapril are less affected by hepatic impairment. Other agents may require dose adjustments. ## Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (including laryngeal edema), acute kidney injury (especially in patients with bilateral renal artery stenosis), severe hypotension, hyperkalemia, rash, neutropenia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially thiazides or loop diuretics):** Increased risk of symptomatic hypotension. Initiate with lower doses and monitor volume status. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. Monitor lithium levels. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use unless under specialist supervision. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in patients with diabetes. ## Monitoring * Blood pressure (including orthostatic changes). * Renal function (serum creatinine, BUN). * Serum potassium. * Signs and symptoms of angioedema. * For patients with heart failure, monitor for worsening symptoms. ## Clinical Pearls * The characteristic dry cough is due to bradykinin accumulation and typically resolves within 1-4 weeks of discontinuation. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. * Initiate with low doses and titrate slowly, especially in elderly patients, those with volume depletion, or renal impairment. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. * Do not initiate ACE inhibitors in patients with bilateral renal artery stenosis due to the risk of severe renal failure. *** *Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete and up-to-date details before making therapeutic decisions.*