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# ACE Inhibitors ## Overview ACE inhibitors are a class of medications primarily 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 (to improve survival) * Diabetic nephropathy (proteinuria reduction) * Certain chronic kidney diseases ## Adult Dosing Dosing varies significantly by specific ACE inhibitor, indication, and patient factors. Titration is common. * **Hypertension:** Usual starting doses are low, with gradual increases. For example, lisinopril: 10 mg PO once daily, titrate up to 20-40 mg PO once daily. Benazepril: 10 mg PO once daily, titrate up to 40 mg PO once daily. Captopril: 25 mg PO twice daily, titrate up to 50 mg PO three times daily. Ramipril: 2.5-5 mg PO once daily, titrate up to 10 mg PO once daily. Max doses vary by agent. * **Heart Failure:** Typical starting doses are lower than for hypertension to avoid hypotension. For example, lisinopril: 5 mg PO once daily, titrate up to 20-40 mg PO once daily. Ramipril: 1.25-2.5 mg PO twice daily, titrate up to 10 mg PO once daily. * **Post-MI:** Initiated within 24 hours in stable patients. Lisinopril: 5 mg PO daily, increased to 10 mg PO daily. Ramipril: 2.5 mg PO twice daily, increased to 5 mg PO twice daily. * **Diabetic Nephropathy:** Ramipril: 10 mg PO once daily is commonly used. ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and certain congenital heart diseases. Dosing is weight-based and varies by agent and indication. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/dose PO every 12-24 hours, not to exceed 20 mg/day. * Lisinopril: 0.07-0.2 mg/kg/dose PO once daily, not to exceed 20 mg/day. * Benazepril: 0.1-0.2 mg/kg/dose PO once daily, not to exceed 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce dose based on creatinine clearance. Monitor potassium closely. * **Hepatic Impairment:** Dose adjustments may be needed, particularly for those with hepatic encephalopathy or severe cirrhosis. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (second and third trimesters) due to risk of fetal injury and death. * Known hypersensitivity to the specific ACE inhibitor. * Hereditary or idiopathic angioedema. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (can be life-threatening, especially involving the airway), acute kidney injury (particularly in volume-depleted or bilateral renal artery stenosis), hypotension, severe hyperkalemia. * **Less Common:** Rash, taste disturbances, neutropenia, renal dysfunction. ## 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 impairment. * **Diuretics (especially loop and thiazide):** Increased risk of hypotension and volume depletion. * **Lithium:** Increased serum lithium levels and risk of toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., saxagliptin, linagliptin):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. ACE inhibitors should not be used within 36 hours of sacubitril/valsartan. ## Monitoring * **Blood Pressure:** Monitor regularly, especially after initiation or dose changes. * **Serum Potassium:** Monitor periodically, especially in patients with renal impairment or those taking potassium supplements/sparing diuretics. * **Renal Function (BUN, Creatinine):** Monitor periodically, especially in patients with pre-existing renal disease or at risk. * **Signs/Symptoms of Angioedema:** Educate patients to report immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and is generally reversible upon discontinuation. * Angioedema can occur at any time during therapy and is a medical emergency. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, elderly, or have significant renal impairment. * Avoid in pregnancy. *** *This information is for educational purposes only and does not constitute medical advice. Always consult current prescribing information and relevant guidelines for specific patient care decisions.*