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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 (systolic dysfunction) * Myocardial infarction (post-MI management) * Diabetic nephropathy ## Adult Dosing Dosing is highly individualized and depends on the specific agent and indication. Titration is generally performed every 1-4 weeks. * **Hypertension:** * Benazepril: Initiate 10 mg once daily, titrate to 20-40 mg once daily. * Captopril: Initiate 25 mg twice daily, titrate to 50 mg three times daily. * Enalapril: Initiate 5 mg once daily, titrate to 10-40 mg once or twice daily. * Fosinopril: Initiate 10 mg once daily, titrate to 20-40 mg once daily. * Lisinopril: Initiate 10 mg once daily, titrate to 20-40 mg once daily. * Moexipril: Initiate 7.5 mg once daily, titrate to 15-30 mg once daily. * Perindopril: Initiate 2.5-5 mg once daily, titrate to 5-10 mg once daily. * Quinapril: Initiate 10 mg once daily, titrate to 20-80 mg once or twice daily. * Ramipril: Initiate 2.5 mg once daily, titrate to 10 mg once daily. * Trandolapril: Initiate 1 mg once daily, titrate to 2-4 mg once daily. * **Heart Failure:** Doses are typically higher than for hypertension. See specific agent recommendations. * **Post-MI:** Generally initiated within 24 hours of MI. See specific agent recommendations. * **Diabetic Nephropathy:** See specific agent recommendations. ## Pediatric Dosing Dosing in pediatric patients is less well-established and often based on weight. Consult pediatric-specific guidelines or prescribing information. * **Hypertension:** * Enalapril: 0.07 mg/kg to 0.75 mg/kg once daily (maximum 40 mg/day). * Lisinopril: 0.07 mg/kg to 0.2 mg/kg once daily (maximum 20 mg/day). * Captopril: 0.3 mg/kg to 0.5 mg/kg three times daily (maximum 150 mg/day). ## Dose Adjustments * **Renal Impairment:** Dose reductions are generally required. Specific recommendations vary by agent and degree of renal impairment (creatinine clearance). * **Hepatic Impairment:** Use with caution; reduced clearance may necessitate dose adjustment. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (teratogenic effects). * Hypersensitivity to ACE inhibitors. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Less Common/Serious:** Angioedema (can be life-threatening), hypotension, renal insufficiency/failure, neutropenia, rash, taste disturbances. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, aspirin:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics (thiazide, loop):** Increased risk of symptomatic hypotension. * **Lithium:** Increased lithium levels and toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs, Aliskiren:** Increased risk of hyperkalemia and renal impairment; avoid concomitant use in certain patient populations (see Contraindications). ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium). * **During therapy:** Blood pressure, serum creatinine, electrolytes (especially potassium), particularly after dose initiation or changes, and in patients with risk factors for renal impairment or hyperkalemia. Monitor for signs/symptoms of angioedema. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and typically resolves after discontinuation. * Angioedema is a rare but serious side effect that can occur at any time during therapy, including after the first dose. Patients should be advised to seek immediate medical attention if swelling of the face, lips, tongue, or throat occurs. * ACE inhibitors should be stopped if angioedema develops. * Careful initiation and titration are important, especially in volume-depleted patients or those with renal artery stenosis, to avoid excessive hypotension or acute renal failure. * ACE inhibitors are generally considered safe and effective in pregnancy, but should be discontinued as soon as pregnancy is detected due to teratogenic risks. *** **Disclaimer:** This information is intended for healthcare professionals and should not replace a thorough review of the most current prescribing information, clinical guidelines, or professional judgment. Dosing and management decisions should be individualized based on patient-specific factors and local protocols.