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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Acute myocardial infarction (in select patients) * Diabetic nephropathy * Chronic kidney disease with proteinuria ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. * **Hypertension:** Initial doses are typically low and titrated upwards every 1-4 weeks as needed to achieve blood pressure goals. * Benazepril: 5-10 mg PO once daily, usual range 10-40 mg/day. * Captopril: 12.5-25 mg PO BID-TID, usual range 25-150 mg/day. * Enalapril: 2.5-5 mg PO BID, usual range 5-40 mg/day. * Fosinopril: 10 mg PO once daily, usual range 20-40 mg/day. * Lisinopril: 5-10 mg PO once daily, usual range 10-40 mg/day. * Moexipril: 7.5 mg PO once daily, usual range 7.5-30 mg/day. * Perindopril: 2.5-5 mg PO once daily, usual range 2.5-20 mg/day. * Quinapril: 5-10 mg PO BID, usual range 10-80 mg/day. * Ramipril: 2.5 mg PO once daily, usual range 2.5-20 mg/day. * Trandolapril: 1 mg PO once daily, usual range 1-4 mg/day. * **Heart Failure:** Dosing is initiated at low doses and titrated carefully to target doses or the maximum tolerated dose. * Enalapril: 2.5 mg PO BID, usual target 10 mg PO BID. * Lisinopril: 5 mg PO once daily, usual target 10-20 mg PO once daily. * Ramipril: 1.25 mg PO once daily, usual target 5 mg PO once daily. * Captopril: 6.25 mg PO TID, usual target 50 mg PO TID. * **Acute Myocardial Infarction:** Therapy is typically initiated within 24 hours of symptom onset in patients without contraindications. * Enalapril: 2.5 mg PO BID (if not hypotensive), followed by 5 mg, 10 mg, and 10 mg PO BID over 2 days. * Captopril: 6.25 mg PO TID, followed by 12.5 mg PO TID, and 25 mg PO TID. * Lisinopril: 5 mg PO once daily, followed by 5 mg, 10 mg, and 10 mg PO once daily over 3 days. ## Pediatric Dosing * **Hypertension:** Dosing is weight-based and varies by agent. Renal function and patient response should guide titration. * Enalapril: 0.07 mg/kg/day PO once daily or BID, not to exceed 0.61 mg/kg/day or adult maximum. * Lisinopril: 0.07 mg/kg/day PO once daily, not to exceed 5 mg/day initially, then titrated up to 0.21 mg/kg/day or adult maximum. * Captopril: 0.3 mg/kg/dose PO TID, not to exceed 0.5 mg/kg/dose or adult maximum. * **Heart Failure:** Dosing is less well-established in children. Consult specialized pediatric cardiology resources. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate slowly. Monitor potassium and renal function closely. In severe impairment, dose reductions may be substantial. * **Hepatic Impairment:** Use with caution. Enalapril and lisinopril are renally eliminated and may require less adjustment than captopril, which is hepatically metabolized. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (Category D in 2nd and 3rd trimesters, Category C in 1st trimester). * Hypersensitivity to ACE inhibitors. * Bilateral renal artery stenosis. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening), hypotension, acute kidney injury, rash, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, trimethoprim:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, especially in volume-depleted patients. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid in patients with diabetes. * **ARBs:** Increased risk of angioedema, hyperkalemia, and renal dysfunction. Generally not recommended to use concurrently. * **Sacubitril/Valsartan:** Concomitant use with ACE inhibitors is contraindicated due to increased risk of angioedema. A washout period is required before initiating sacubitril/valsartan if an ACE inhibitor was recently used. ## Monitoring * **Blood Pressure:** Regularly monitor at home and in clinic. * **Renal Function:** Monitor serum creatinine and BUN, especially at initiation, dose changes, and in patients with risk factors. * **Serum Potassium:** Monitor regularly, especially in patients with renal impairment, diabetes, or on concomitant potassium-retaining agents. * **Angioedema Symptoms:** Educate patients to report swelling of the face, lips, tongue, or throat immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an ARB. * Initiate at a low dose and titrate slowly, especially in patients who are elderly, volume-depleted, or have renal impairment. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Discontinue immediately if angioedema occurs. * Use with caution in patients with a history of angioedema from other causes. *** **Disclaimer:** This information is intended for healthcare professionals and does not replace official prescribing information. Always verify current drug information, dosages, and safety guidelines from reputable sources, including the FDA-approved product labeling, before making any clinical decisions.