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# ACE Inhibitors ## Overview ACE inhibitors (e.g., lisinopril, enalapril, ramipril) are a class of medications primarily used to manage cardiovascular and renal conditions by blocking the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (HF) * Post-myocardial infarction (MI) * Diabetic nephropathy * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is common. * **Hypertension:** Typically starts at a low dose and titrates up every 1-2 weeks. * Lisinopril: Initial 10 mg PO once daily; usual range 10-40 mg PO once daily. Max 40 mg/day. * Enalapril: Initial 5 mg PO once daily or BID; usual range 10-40 mg PO once daily or divided BID. Max 40 mg/day. * Ramipril: Initial 2.5 mg PO once daily; usual range 2.5-20 mg PO once daily. Max 20 mg/day. * **Heart Failure:** * Enalapril: Initial 2.5 mg PO BID; usual range 5-20 mg PO BID. Max 20 mg/day. * Lisinopril: Initial 5 mg PO once daily; usual range 10-40 mg PO once daily. Max 40 mg/day. * Ramipril: Initial 2.5 mg PO BID; usual range 5-10 mg PO BID. Max 10 mg/day. * **Post-MI:** * Lisinopril: Initiated within 24 hours in hemodynamically stable patients. 5 mg PO once daily, followed by 5 mg PO once daily after 24 hours, then 10 mg PO once daily. Continue for at least 6 weeks. * Ramipril: Initial 2.5 mg PO BID; usual range 5 mg PO BID. ## Pediatric Dosing Established pediatric dosing is available for some agents and indications, often requiring careful titration and monitoring. Refer to specific guidelines or product information. * **Hypertension:** * Enalapril: 3 months to 16 years: 0.08 mg/kg PO once daily (range 0.07-0.6 mg/kg/day divided QD or BID). Max 40 mg/day. * Lisinopril: 6 to 12 years: 0.07-0.1 mg/kg PO once daily. Max 20 mg/day. (Limited data for younger children). ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in patients with significant renal dysfunction. Monitor potassium and creatinine closely. * **Hepatic Impairment:** Use with caution, as hepatic metabolism can be reduced. * **Volume Depletion:** Initiate at lower doses and monitor closely for hypotension. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (especially in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (AKI), hypotension, severe hyperkalemia, 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 dysfunction. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **Lithium:** Increased lithium levels and risk of toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., saxagliptin, linagliptin):** Increased risk of angioedema. * **ARBs, Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. ## Monitoring * **Baseline:** Blood pressure, renal function (serum creatinine, BUN), electrolytes (serum potassium). * **During Therapy:** Blood pressure, renal function, electrolytes (especially potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. Monitor for signs/symptoms of angioedema or cough. ## Clinical Pearls * Cough is a common, dose-limiting side effect but does not typically indicate significant toxicity. Switch to an ARB if cough is intolerable. * Angioedema can occur at any time during therapy and requires immediate discontinuation of the ACE inhibitor and emergency medical attention. * Initiate at the lowest effective dose, especially in patients who are volume-depleted, on diuretics, or have renal impairment. * ACE inhibitors can be renoprotective in patients with diabetes and proteinuria. * First-dose hypotension can occur, particularly in patients taking diuretics or with severe heart failure. Advise patients to take the first dose at bedtime. *** *Disclaimer: This information is for educational purposes only and does not substitute for professional medical advice. Always verify current prescribing information and consult with a healthcare provider for any medical concerns or before making any treatment decisions.*