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# ACE Inhibitors ## Overview ACE inhibitors (e.g., enalapril, lisinopril, ramipril) are a class of medications that block the action of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (for patients with clinical signs of heart failure or LV dysfunction) * Diabetic nephropathy (in patients with type 1 diabetes and hypertension) ## Adult Dosing * **Hypertension:** Dosing varies by agent. Typical starting doses: * Enalapril: 5 mg once or twice daily. Maximum: 40 mg/day. * Lisinopril: 10 mg once daily. Maximum: 40 mg/day. * Ramipril: 2.5 mg once daily. Maximum: 10 mg/day. * **Heart Failure:** Dosing varies by agent and clinical status. * Enalapril: Starting dose 2.5 mg twice daily, titrate up to target dose of 10 mg twice daily. Maximum: 20 mg twice daily. * Lisinopril: Starting dose 5 mg once daily, titrate up to target dose of 10 mg once daily. Maximum: 35 mg once daily. * Ramipril: Starting dose 1.25 mg once daily, titrate up to target dose of 5 mg twice daily. Maximum: 10 mg/day. * **Post-MI:** Typically initiated within 24 hours in stable patients. * Enalapril: 2.5 mg twice daily, increased to 5 mg twice daily, then to 10 mg twice daily if tolerated. * Lisinopril: 5 mg once daily, increased to 10 mg once daily, then to 20 mg once daily if tolerated. * **Diabetic Nephropathy:** Dosing varies by agent and specific indication. Dose titration is typically based on clinical response and tolerability, often over weeks. ## Pediatric Dosing * **Hypertension:** Dosing is highly variable by agent and age. Local protocols should be consulted. * Enalapril: 0.07 mg/kg/day once daily (up to 5 mg/day) in infants and children. Maximum: 0.61 mg/kg/day (up to 40 mg/day). * Lisinopril: Starting dose 0.07 mg/kg/day once daily (up to 5 mg/day). Titrate based on response and tolerability. Maximum: 0.61 mg/kg/day (up to 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. * For agents with typical starting doses: * Creatinine clearance (CrCl) < 30 mL/min: Reduce initial dose by at least half. * CrCl 30-40 mL/min: Consider reducing initial dose. * Consult specific agent monographs for detailed recommendations. * **Hepatic Impairment:** Use with caution. Enalapril may require reduced dosing. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Concomitant use with sacubitril/valsartan within 36 hours of the last dose of an ACE inhibitor. * Pregnancy (contraindicated in 2nd and 3rd trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (can be life-threatening), hypotension, acute kidney injury, hyperkalemia, neutropenia, liver injury. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **Lithium:** ACE inhibitors can increase lithium levels. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. * **Sacubitril/valsartan:** Increased risk of angioedema. ## Monitoring * **Baseline:** Renal function (serum creatinine, BUN), electrolytes (serum potassium), blood pressure. * **During therapy:** * Serum creatinine and potassium within 1-2 weeks of initiating therapy or dose increase, and periodically thereafter. * Blood pressure regularly. * Signs/symptoms of angioedema or other hypersensitivity reactions. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an ARB. * ACE inhibitors are generally considered safe and effective in pregnancy, but they are **contraindicated** in the second and third trimesters due to the risk of fetal injury or death. * Initiate at low doses, especially in patients who are volume-depleted, on diuretics, or have renal impairment, to minimize the risk of profound hypotension. * Monitor potassium closely, particularly in patients with renal insufficiency, diabetes, or those taking potassium supplements or potassium-sparing diuretics. *** Please verify the current prescribing information for the specific agent being used and consult institutional protocols for definitive dosing and management guidance.