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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (in select patients) * Diabetic nephropathy ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically required. * **Hypertension:** Initial doses are usually low, with gradual increases every 1-2 weeks as needed. * *Examples:* * Lisinopril: 10 mg orally once daily, titrate up to 40 mg once daily. * Enalapril: 5 mg orally once or twice daily, titrate up to 40 mg once or twice daily. * Ramipril: 2.5 mg orally once daily, titrate up to 10 mg once daily. * **Heart Failure:** Dosing often starts lower than for hypertension and is titrated up to target doses as tolerated. * *Examples:* * Enalapril: 2.5 mg orally twice daily, titrate up to 10-20 mg orally twice daily. * Ramipril: 1.25 mg orally once daily, titrate up to 5 mg orally twice daily. * **Post-MI:** Typically initiated within 24 hours in hemodynamically stable patients. * *Example:* Lisinopril: 5 mg orally once daily, followed by 5 mg after 24 hours, then 10 mg once daily thereafter. ## Pediatric Dosing Dosing in pediatrics is weight-based and may vary by product and indication. Consult specific pediatric guidelines. * **Hypertension:** * *Enalapril:* 0.07 mg/kg orally once daily, maximum 0.61 mg/kg/day or 40 mg/day. * *Lisinopril:* 0.07 mg/kg orally once daily, maximum 0.61 mg/kg/day or 40 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate carefully. * *Captopril:* If serum creatinine > 3 mg/dL, reduce dose by half. * *Enalapril:* If serum creatinine > 3 mg/dL, initial dose 5 mg. * *Lisinopril:* If serum creatinine < 30 mL/min, start at 2.5-5 mg daily. If serum creatinine 30-80 mL/min, start at 5 mg daily. * **Hepatic Impairment:** Use with caution; initiation of therapy may be slower. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (Category D, especially in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (including laryngeal edema), acute kidney injury, severe hypotension, hyperkalemia. * **Less Common:** Rash, taste disturbances, neutropenia, agranulocytosis. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone:** Increased risk of hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May blunt antihypertensive effect and increase risk of renal dysfunction, especially in volume-depleted patients. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly assess for hypotension. * **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and with dose changes or in patients with risk factors. * **Serum Potassium:** Monitor regularly, especially in patients with renal impairment, diabetes, or those taking potassium supplements/sparing diuretics. * **Angioedema:** 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. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB). * Start with low doses and titrate slowly, particularly in elderly patients, those with heart failure, or renal impairment. * ACE inhibitors are generally considered renoprotective in diabetic patients with proteinuria. * Discontinue ACE inhibitor if angioedema occurs and never re-challenge. * Advise patients to avoid potassium supplements and salt substitutes containing potassium unless directed by a healthcare provider. *** *This information is intended for clinical use and is not a substitute for professional medical advice. Always verify the most current prescribing information with official drug compendia or the manufacturer's labeling.*