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# ACE Inhibitors ## Overview ACE inhibitors (ACEIs) 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, thereby leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (in select patients) * Diabetic nephropathy (proteinuria) * Chronic kidney disease (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACEI, indication, and patient response. Common starting doses for *hypertension* are often low and titrated upwards. * **Benazepril:** Start 10 mg once daily, titrate to 20-40 mg/day. * **Captopril:** Start 25 mg twice daily, titrate to 50-150 mg/day in divided doses. (May be given TID). * **Enalapril:** Start 5 mg once daily, titrate to 10-40 mg/day in one or two divided doses. * **Fosinopril:** Start 10 mg once daily, titrate to 20-40 mg/day. * **Lisinopril:** Start 10 mg once daily, titrate to 20-40 mg/day. * **Moexipril:** Start 7.5 mg once daily, titrate to 15-30 mg/day. * **Perindopril:** Start 5 mg once daily, titrate to 10 mg/day. (Higher doses may be used for heart failure). * **Quinapril:** Start 10 mg once or twice daily, titrate to 20-80 mg/day in two divided doses. * **Ramipril:** Start 2.5 mg once daily, titrate to 5-10 mg/day. * **Trandolapril:** Start 1 mg once daily, titrate to 2-4 mg/day. For *heart failure*, common starting doses are often lower and titration is more gradual, with maximum doses potentially higher than for hypertension. Consult specific guidelines. ## Pediatric Dosing ACE inhibitors are used in pediatric populations, but dosing is highly variable and often based on weight. Specific protocols or expert consultation are recommended. * **Enalapril:** 0.07-0.1 mg/kg/day once or twice daily, maximum 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** Start 0.07 mg/kg/day once daily, maximum 0.61 mg/kg/day or 20 mg/day. * **Captopril:** Start 0.3 mg/kg/dose three times daily, titrate up to 0.5 mg/kg/dose three times daily, maximum 1.5 mg/kg/day or 150 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is typically required, especially for enalapril, lisinopril, and ramipril. The degree of reduction depends on the specific ACEI and the severity of renal impairment (e.g., creatinine clearance). * **Hepatic Impairment:** Use with caution. Captopril and enalapril may require dose adjustments. ## Contraindications * History of angioedema related to prior ACEI treatment * Hereditary or idiopathic angioedema * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (teratogenic risk, especially in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hyperkalemia, fatigue, headache, hypotension. * **Serious:** Angioedema (potentially life-threatening), renal dysfunction (especially in patients with bilateral renal artery stenosis), neutropenia/agranulocytosis (rare), hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics/Potassium supplements/ARBs/Aliskiren:** Increased risk of hyperkalemia. * **NSAIDs/COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Lithium:** Increased lithium levels and toxicity. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension, particularly after initiation of ACEI therapy. * **Mammalian target of rapamycin (mTOR) inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor for hypotension. * **Renal Function:** Monitor serum creatinine and BUN, especially at baseline and with dose changes. * **Potassium:** Monitor serum potassium, especially in patients with renal impairment or those taking potassium-sparing diuretics. * **Angioedema:** Educate patients to report any signs of angioedema immediately. ## Clinical Pearls * The characteristic dry cough is a common reason for discontinuation but is reversible. * Angioedema can occur at any time during therapy and is a medical emergency. * ACEIs are generally renoprotective in patients with proteinuria. * Initiate at low doses and titrate slowly, especially in patients with volume depletion, renal impairment, or on diuretics. * If angioedema occurs, discontinue the ACEI immediately and do not re-challenge. *** *Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for complete details, including specific indications, contraindications, warnings, precautions, adverse reactions, drug interactions, and dosing recommendations. Dosing may vary based on local protocols and individual patient factors.*