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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that block the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone secretion. This results in lower blood pressure and reduced cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (for patients with clinical signs of heart failure or LV dysfunction) * Diabetic nephropathy (to slow the progression) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor and indication. Titration is typically guided by blood pressure response and tolerability. * **Hypertension:** Usual starting doses for common agents include: * Lisinopril: 10 mg orally once daily * Enalapril: 5 mg orally once or twice daily * Ramipril: 2.5 mg orally once daily * Benazepril: 10 mg orally once daily * Captopril: 25 mg orally twice daily * Maximal doses vary by agent but often range from 20-40 mg daily for lisinopril, 10-20 mg BID for enalapril, and 10 mg daily for ramipril. * **Heart Failure:** Usual starting doses for common agents include: * Lisinopril: 5 mg orally once daily (target 10-40 mg daily) * Enalapril: 2.5 mg orally twice daily (target 10-20 mg BID) * Ramipril: 2.5 mg orally once daily (target 10 mg daily) * **Post-MI:** Usual starting doses for common agents include: * Lisinopril: 5 mg orally once daily, with subsequent doses of 5 mg, 10 mg, and 20 mg daily over 4 weeks (if tolerated) * Ramipril: 2.5 mg orally twice daily, with subsequent doses of 5 mg and 10 mg BID over 4 weeks (if tolerated) ## Pediatric Dosing Dosing in pediatric patients is less established and often based on weight. Titration is crucial and guided by blood pressure response. Specific protocols should be consulted. * **Hypertension:** * Enalapril: 0.08 mg/kg/day orally once daily, not to exceed 0.5 mg/kg/day or adult maximum dose. * Lisinopril: 0.07 mg/kg/day orally once daily, not to exceed 0.61 mg/kg/day or adult maximum dose. ## Dose Adjustments * **Renal Impairment:** Dose reduction is typically required. Specific adjustments depend on the degree of renal impairment and the specific ACE inhibitor. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Use with caution. Enalapril dosing may need to be reduced. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment * Concomitant use with aliskiren in patients with diabetes or renal impairment * Pregnancy (especially second and third trimesters) ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, rash, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, aliskiren, ARBs:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in elderly patients or those with volume depletion. * **Diuretics (thiazide, loop):** Increased risk of hypotension and volume depletion. May need to temporarily stop diuretic or start ACE inhibitor at a lower dose. * **Lithium:** Increased lithium levels and risk of toxicity. Monitor lithium levels. * **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 and with dose changes, and in patients with renal impairment) * Signs and symptoms of angioedema ## Clinical Pearls * A dry cough is a common side effect and may necessitate discontinuation or switching to an ARB. * Initiate at a low dose and titrate slowly, especially in patients who are volume depleted, on diuretics, or have renal impairment. * The first dose can cause significant hypotension, particularly in patients with heart failure or those on diuretics. Consider a lower starting dose and monitoring. * ACE inhibitors are generally considered renoprotective in diabetic nephropathy. * Angioedema can occur at any time during treatment and is a medical emergency. *** *This information is for educational purposes only and does not constitute medical advice. Always consult the most current prescribing information or a qualified healthcare professional for any questions regarding drug therapy. Dosing recommendations may vary based on specific patient factors and local protocols.*