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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, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI management) * Diabetic nephropathy * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is typically performed every 1-4 weeks. * **Hypertension:** Usual starting doses vary. For example: * Lisinopril: 10 mg once daily. Maximum: 40 mg once daily. * Enalapril: 5 mg once or twice daily. Maximum: 20 mg twice daily. * Ramipril: 2.5 mg once daily. Maximum: 10 mg once daily. * **Heart Failure:** * Lisinopril: 5 mg once daily, titrate up to 20-40 mg once daily. * Enalapril: 2.5 mg twice daily, titrate up to 10-20 mg twice daily. * Ramipril: 1.25 mg once daily, titrate up to 10 mg once daily. * **Post-MI:** Typically initiated within 24 hours in stable patients. * Captopril: 6.25 mg three times daily, then titrate up to 12.5 mg three times daily, then 25 mg three times daily. * Lisinopril: 5 mg once daily, then 10 mg once daily, then titrate to target dose of 10 mg once daily. ## Pediatric Dosing ACE inhibitors are approved for hypertension in pediatric patients, but specific dosing varies by age and weight. Consult pediatric guidelines or specific drug monographs. * **Benazepril:** 0.1 mg/kg/day to 0.6 mg/kg/day divided BID. Max 0.6 mg/kg/day or 40 mg/day. * **Enalapril:** 0.07 mg/kg/dose IV/PO q12h. Max 0.57 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07 mg/kg/day to 0.21 mg/kg/day qDay. Max 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Initial doses should be reduced in patients with renal insufficiency. Dose adjustments may be necessary based on creatinine clearance. * Lisinopril: CrCl < 30 mL/min, start 2.5-5 mg daily. * Ramipril: CrCl < 40 mL/min, start 1.25 mg daily. * **Hepatic Impairment:** Use with caution; reduced clearance may occur. * **Volume Depletion:** Initiate at lower doses or temporarily discontinue if significant volume depletion is present. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes. * Second and third trimesters of pregnancy. ## Adverse Effects Common: * Cough (dry, persistent) * Dizziness, lightheadedness * Fatigue * Headache * Hypotension (especially with first dose or in volume-depleted patients) Serious: * Angioedema (can be life-threatening, especially of the airway) * Hyperkalemia * Acute kidney injury (especially in patients with bilateral renal artery stenosis) * Hepatotoxicity * Neutropenia/agranulocytosis (rare) ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics (non-potassium sparing):** Increased risk of hypotension and renal dysfunction, especially with initial doses. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use in patients with diabetes. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor to assess efficacy and detect hypotension. * **Renal Function (SCr, eGFR):** Baseline and periodically, especially in patients with renal impairment or risk factors. * **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment or taking potassium-sparing agents. * **Angioedema:** Educate patients to report any swelling, especially of the face, lips, tongue, or throat. ## Clinical Pearls * The characteristic dry cough is often the reason for discontinuation, but angioedema is a more serious reason. * Initiate with low doses and titrate slowly, particularly in patients with heart failure, elderly patients, or those with renal impairment. * Monitor for first-dose hypotension, especially in volume-depleted patients or those on diuretics. * ACE inhibitors are generally considered safe and effective in patients with diabetes and proteinuria, as they can slow the progression of nephropathy. * If angioedema occurs, ACE inhibitor therapy must be permanently discontinued, and prompt medical attention is required. --- ***Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines before making any clinical decisions.*