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# ACE Inhibitors ## Overview ACE inhibitors (ACEIs) are a class of medications that block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This action leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (left ventricular dysfunction) * Diabetic nephropathy (proteinuria) * Chronic kidney disease (proteinuria) ## Adult Dosing Dosing varies significantly by agent and indication. Titration is typically based on patient response and tolerability. * **Hypertension:** Initial doses are low and titrated upwards. Examples: * Lisinopril: 10 mg once daily, titrate up to 40 mg once daily. * Enalapril: 5 mg once or twice daily, titrate up to 10-40 mg once or twice daily. * Ramipril: 2.5 mg once daily, titrate up to 10 mg once daily. * **Heart Failure:** Dosing is initiated at low levels and gradually increased. Examples: * Lisinopril: 5 mg once daily, titrate up to 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:** Initiated within 24 hours of MI in hemodynamically stable patients. Examples: * Lisinopril: 5 mg once daily, followed by 10 mg once daily, and then maintained at 10 mg once daily. * Captopril: 6.25 mg three times daily, increased to 12.5 mg three times daily, then 25 mg three times daily. * **Diabetic Nephropathy/CKD:** Dosing similar to hypertension, aiming for maximal tolerated dose to reduce proteinuria. ## Pediatric Dosing * **Hypertension:** * Enalapril: 0.07 to 0.1 mg/kg/dose orally once or twice daily. Maximum: 0.5 mg/kg/day or 20 mg/day. * Lisinopril: 0.07 to 0.2 mg/kg/dose orally once daily. Maximum: 20 mg/day. * Captopril: 0.3 mg/kg/dose orally three times daily. Maximum: 4.5 mg/kg/day or 150 mg/day. * Dosing may vary based on formulation (e.g., oral vs. IV enalaprilat). ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate slowly. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Use with caution, particularly with hepatic encephalopathy. May require dose reduction. ## Contraindications * History of angioedema related to ACEI therapy. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to ACE inhibitors. * Hereditary or idiopathic angioedema. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, headache, fatigue. * **Serious:** Angioedema (lips, tongue, larynx, intestines), acute kidney injury (especially in bilateral renal artery stenosis), hyperkalemia, elevated liver enzymes, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients or those with pre-existing renal dysfunction. * **Diuretics (especially loop and thiazide):** Increased risk of symptomatic hypotension, especially upon initiation. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in diabetic patients. * **ARBs:** Increased risk of hyperkalemia, renal dysfunction, and angioedema. Avoid concomitant use. * **Lithium:** ACEIs can reduce lithium clearance, increasing the risk of lithium toxicity. Monitor lithium levels closely. * **mTOR inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly, especially during titration. * **Renal Function:** Serum creatinine and BUN, particularly at baseline, after dose increases, and in patients with renal impairment or at risk. * **Serum Potassium:** Regularly, especially in patients with renal impairment, diabetes, or those taking potassium-sparing agents. * **Signs/Symptoms of Angioedema:** Educate patients on recognizing and reporting symptoms immediately. ## Clinical Pearls * Cough is a common, dose-limiting side effect. If persistent and bothersome, consider switching to an ARB. * Hypotension is most likely with the first few doses or after dose increases, particularly in volume-depleted patients or those on diuretics. Administer first dose with caution. * First-dose hypotension can be managed by starting at a lower dose, withholding diuretics temporarily, and ensuring adequate hydration. * ACEIs are renoprotective in patients with diabetes and proteinuria. * Angioedema is a medical emergency. Discontinue ACEI immediately and manage airway. * Discontinue ACEI if pregnancy is planned or confirmed. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive dosing, indications, contraindications, and safety information before prescribing any medication. Local protocols may dictate specific dosing strategies.