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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat hypertension and heart failure, among other conditions. 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 (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (in patients with diabetes and hypertension or proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is typically performed every 1-4 weeks. * **Hypertension:** * Benazepril: 5-40 mg once daily. Max: 80 mg daily. * Captopril: 25 mg twice daily initially. Titrate to 50 mg three times daily. Max: 150 mg three times daily. * Enalapril: 5-20 mg once daily initially. Titrate to 10-40 mg once or twice daily. Max: 40 mg daily. * Fosinopril: 10-40 mg once daily. Max: 80 mg daily. * Lisinopril: 10 mg once daily initially. Titrate to 20-40 mg once daily. Max: 80 mg daily. * Moexipril: 7.5-15 mg once or twice daily. Max: 30 mg daily. * Perindopril: 2.5-10 mg once daily. Max: 20 mg daily. * Quinapril: 10-40 mg once or twice daily. Max: 80 mg daily. * Ramipril: 2.5-5 mg once daily initially. Titrate to 10 mg once daily. Max: 20 mg daily. * Trandolapril: 0.5-4 mg once daily. Max: 4 mg daily. * **Heart Failure:** * Captopril: 6.25 mg three times daily initially. Titrate to target dose of 50 mg three times daily. * Enalapril: 2.5 mg twice daily initially. Titrate to target dose of 10-20 mg twice daily. * Lisinopril: 5 mg once daily initially. Titrate to target dose of 20-40 mg once daily. * Ramipril: 1.25 mg once daily initially. Titrate to target dose of 5 mg twice daily or 10 mg once daily. * **Post-MI:** * Captopril: 6.25 mg three times daily, increasing to 12.5 mg three times daily, then 25 mg three times daily. * Enalapril: 2.5 mg twice daily, increasing to 5 mg twice daily, then 10 mg twice daily. * Lisinopril: 5 mg once daily, increasing to 10 mg once daily, then 20 mg once daily. * Ramipril: 1.25 mg once daily, increasing to 2.5 mg twice daily, then 5 mg twice daily. ## Pediatric Dosing * **Hypertension:** Dosing varies by age and weight and is often initiated at lower doses with titration based on response. Consult specific pediatric guidelines for precise dosing. * Enalapril: 0.07 mg/kg/day divided once or twice daily. Max: 0.61 mg/kg/day or 40 mg/day. * Lisinopril: 0.07 mg/kg/day once daily. Max: 40 mg/day. * Ramipril: 0.05-0.1 mg/kg/day once daily. Max: 10 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in severe renal impairment. Specific recommendations vary by agent and degree of renal dysfunction. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Use with caution. Captopril and enalapril are less affected by hepatic impairment than prodrugs like benazepril, lisinopril, and quinapril. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes. * Concomitant use with sacubitril/valsartan within 36 hours. * Pregnancy (Category D). ## Adverse Effects * **Common:** Cough (dry, persistent), hyperkalemia, dizziness, fatigue, headache, hypotension. * **Serious:** Angioedema (including laryngeal edema), acute kidney injury, rash, neutropenia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **Diuretics (thiazide or loop):** Additive hypotensive effect. May also increase risk of symptomatic hypotension. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. ## Monitoring * Blood pressure * Serum potassium * Serum creatinine and BUN (especially at initiation, dose increase, or in patients with renal impairment) * Signs and symptoms of angioedema or hypersensitivity ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB). * Angioedema is a rare but life-threatening side effect. Promptly discontinue ACE inhibitors if angioedema occurs. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, have heart failure, or renal impairment, to minimize risk of hypotension and acute kidney injury. * ACE inhibitors are generally considered safe and effective in pregnancy, but they are contraindicated in the second and third trimesters due to potential for fetal harm. --- ***Disclaimer:** This information is for educational purposes only and does not constitute medical advice. Always verify current prescribing information with official drug references and consult with a qualified healthcare professional for any medical decisions.*