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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, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (MI) * Diabetic nephropathy * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Typical starting doses are low and titrated upwards. * **Hypertension:** * Benazepril: 5-10 mg PO once daily, maximum 40 mg/day. * Captopril: 12.5-25 mg PO twice daily, maximum 150 mg/day. * Enalapril: 5-10 mg PO once daily, maximum 40 mg/day. * Fosinopril: 10 mg PO once daily, maximum 80 mg/day. * Lisinopril: 5-10 mg PO once daily, maximum 40 mg/day. * Moexipril: 7.5 mg PO once daily, maximum 30 mg/day. * Perindopril: 2.5-5 mg PO once daily, maximum 10 mg/day. * Quinapril: 5-10 mg PO once or twice daily, maximum 80 mg/day. * Ramipril: 2.5-5 mg PO once daily, maximum 10 mg/day. * Trandolapril: 1 mg PO once daily, maximum 4 mg/day. * **Heart Failure:** Dosing is often higher than for hypertension, with specific titration schedules recommended. Consult individual drug monographs. * **Post-MI:** Typically started within 24 hours of MI in stable patients. Dosing varies by agent, usually with gradual titration. * **Diabetic Nephropathy/CKD with Proteinuria:** Dosing is similar to hypertension, aiming for blood pressure control and reduction in proteinuria. ## Pediatric Dosing * **Hypertension:** Established for some ACE inhibitors. * Enalapril: 0.07 mg/kg/day to 0.5 mg/kg/day PO divided once or twice daily. * Lisinopril: 0.07 mg/kg/day to 0.5 mg/kg/day PO once daily. * Captopril: 0.3 mg/kg/dose PO three times daily. * Dosing in neonates and infants should be initiated with caution and at the lower end of the recommended range. ## Dose Adjustments * **Renal Impairment:** Dosage reduction is often required, especially for renally eliminated ACE inhibitors (e.g., enalapril, lisinopril). Specific guidelines vary by drug and degree of renal impairment. * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or moderate to severe renal impairment. * Pregnancy (teratogenic, especially in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (can be life-threatening), acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), hypotension, rash, neutropenia, elevated liver enzymes. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients. * **Diuretics (especially thiazides or loop diuretics):** Increased risk of hypotension, particularly with first-dose therapy. * **Lithium:** ACE inhibitors can increase lithium levels, leading to toxicity. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid in patients with diabetes. * **Mammalian Target of Rapamycin (mTOR) inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor for efficacy and hypotension. * **Serum Potassium:** Monitor periodically, especially in patients with renal impairment or those on potassium-sparing agents. * **Renal Function (serum creatinine, BUN):** Monitor periodically, especially at initiation of therapy or with dose changes. * **Angioedema:** Educate patients to report any swelling of the face, lips, tongue, or throat immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. * Angioedema can occur at any time during therapy and is a medical emergency. Discontinue ACE inhibitor immediately if angioedema is suspected. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Initiate at low doses and titrate slowly to minimize hypotension and other side effects. * Avoid use in pregnancy due to teratogenicity. Counsel patients of childbearing potential. *** *Disclaimer: This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for complete details.*