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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (in selected patients) * Diabetic nephropathy (proteinuria) ## Adult Dosing Dosing is highly variable by agent and indication. Titration is typically guided by blood pressure response, clinical signs of heart failure, or degree of proteinuria. * **Hypertension:** Initial doses are usually low and titrated upwards every 2-4 weeks. * *Example:* Lisinopril: Start 10 mg once daily, titrate up to 40 mg once daily. * *Example:* Ramipril: Start 2.5 mg once daily, titrate up to 10 mg once daily. * **Heart Failure:** Start at low doses and titrate upwards as tolerated, usually over several weeks. * *Example:* Enalapril: Start 2.5 mg twice daily, titrate up to target dose of 10-20 mg twice daily. * *Example:* Lisinopril: Start 5 mg once daily, titrate up to target dose of 20-40 mg once daily. * **Post-MI:** Typically initiated within 24 hours of MI in hemodynamically stable patients. * *Example:* Ramipril: Start 2.5 mg twice daily, increase to 5 mg twice daily after 1 day, then to 10 mg twice daily after 4 weeks. * **Diabetic Nephropathy:** * *Example:* Lisinopril: Start 10 mg once daily, titrate up to 20 mg once daily or maximum tolerated dose. ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and sometimes heart failure. Dosing is often based on weight and may vary by agent. Consult specific pediatric guidelines or drug monographs. * *Example:* Enalapril (Hypertension): 0.08 mg/kg/day to 0.3 mg/kg/day divided every 12-24 hours. Maximum dose 40 mg/day. * *Example:* Captopril (Hypertension): 0.3 mg/kg/dose every 8 hours initially, may increase to 0.5 mg/kg/dose every 6-8 hours. Maximum dose 4.5 mg/kg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially with low GFR. Monitor potassium and serum creatinine. * **Hepatic Impairment:** Generally do not require dose adjustment unless severe. ## Contraindications * History of angioedema related to prior ACE inhibitor use. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (especially in the second and third trimesters). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Dry Cough:** Common, often dose-related. * **Angioedema:** Rare but potentially life-threatening; may occur at any time. Discontinue immediately if suspected. * **Hyperkalemia:** Increased risk in patients with renal impairment or those taking potassium-sparing diuretics or potassium supplements. * **Hypotension:** Particularly with the first dose or in volume-depleted patients. * **Renal Dysfunction:** Can occur, especially in patients with bilateral renal artery stenosis. Monitor renal function and potassium. * **Dizziness, Fatigue, Headache.** * **Taste disturbances.** * **Rash.** ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride), Potassium supplements, Salt substitutes:** Increased risk of hyperkalemia. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use, especially in patients with diabetes. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (especially thiazide diuretics):** Increased risk of hypotension. May require dose adjustment of either agent. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. Monitor lithium levels. * **Sacubitril/Valsartan:** Avoid initiating ACE inhibitor within 36 hours of stopping sacubitril/valsartan. Concurrent use increases risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly, especially during initiation and titration. * **Serum Potassium:** Before initiation, shortly after initiation, and periodically thereafter, especially in patients with renal impairment or on other agents affecting potassium. * **Serum Creatinine/Renal Function:** Before initiation, periodically thereafter, and especially in patients with renal impairment or risk factors for renal compromise. * **Signs/Symptoms of Angioedema:** Counsel patients to report immediately. ## Clinical Pearls * Start low and titrate slowly to minimize first-dose hypotension and other adverse effects. * Dry cough is a common reason for discontinuation but is usually reversible upon stopping the medication. * Angioedema is a medical emergency. If suspected, discontinue the ACE inhibitor immediately and do not rechallenge. * Be cautious in patients with bilateral renal artery stenosis or single functioning kidney, as ACE inhibitors can precipitate acute renal failure. * Consider alternative antihypertensives if cough is intolerable and no other cause is found. * ACE inhibitors are generally safe and effective in patients with diabetes, offering renal protection. *** This information is intended for healthcare professionals. Always verify current prescribing information and consult specific product monographs or clinical guidelines for comprehensive details.