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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications primarily used for managing cardiovascular conditions. 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 (to improve survival) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is essential. * **Hypertension:** Usual starting doses include benazepril 10 mg once daily, captopril 25 mg twice daily, enalapril 5 mg once daily, lisinopril 10 mg once daily, ramipril 2.5 mg once daily. Maximum doses vary by agent (e.g., lisinopril up to 40 mg daily, enalapril up to 40 mg daily). * **Heart Failure:** Usual starting doses include enalapril 2.5 mg twice daily, lisinopril 5 mg once daily, ramipril 1.25 mg once daily. Doses are typically titrated up to target doses (e.g., enalapril 10-20 mg twice daily, lisinopril 20-40 mg once daily, ramipril 5 mg twice daily), depending on patient tolerance and blood pressure. * **Post-MI:** Generally initiated within 24 hours of STEMI in hemodynamically stable patients. Lisinopril 5 mg once daily, increasing to 10 mg once daily. Other ACE inhibitors can be used at appropriate doses. * **Diabetic Nephropathy:** Ramipril 10 mg once daily is often used. ## Pediatric Dosing ACE inhibitors are used in pediatric populations for hypertension and certain other conditions, but specific dosing can be complex and is often based on weight. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/day once daily or divided BID. Max: 0.61 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/day once daily. Max: 40 mg/day. * Captopril: 0.3-0.5 mg/kg/dose TID. Max: 4.5 mg/kg/day or 300 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in severe renal impairment (CrCl <30 mL/min). Captopril and enalapril require more significant adjustments. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Cautious initiation and titration. ## Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (especially in the second and third trimesters). ## Adverse Effects * **Common:** Dry cough (most frequent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), renal impairment/failure (especially in patients with bilateral renal artery stenosis), severe hypotension, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium:** Increased risk of hyperkalemia. * **NSAIDs (including aspirin):** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Diuretics:** Additive hypotensive effect. May increase risk of renal dysfunction. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium levels and toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in patients with diabetes. ## Monitoring * **Baseline:** Renal function (serum creatinine, BUN), electrolytes (serum potassium), blood pressure. * **During Therapy:** * Renal function and electrolytes within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Blood pressure regularly. * Signs and symptoms of angioedema. ## Clinical Pearls * The dry cough is thought to be due to bradykinin accumulation and typically resolves within 1-4 weeks after discontinuation. * Hypotension can occur, especially with the first dose or in volume-depleted patients. Consider a lower starting dose and gradual titration. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria, but careful monitoring of renal function and potassium is crucial. * Angioedema is a rare but serious side effect; patients should be educated to discontinue the medication immediately and seek emergency care if symptoms develop. *** *This information is intended for healthcare professionals and does not replace the need to consult current prescribing information, clinical guidelines, or local protocols for definitive patient management.*