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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart failure by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. ## Primary Indications * Hypertension * Heart Failure (NYHA Class II-IV) * Left Ventricular Dysfunction post-Myocardial Infarction * Diabetic Nephropathy (in patients with diabetes and hypertension or proteinuria) ## Adult Dosing * **Hypertension:** Initial doses vary by agent. Common starting doses include: * Lisinopril: 10 mg orally once daily. * Enalapril: 5 mg orally once or twice daily. * Ramipril: 2.5 mg orally once daily. * Maximum dose varies by agent, often 40 mg daily for lisinopril and enalapril, 10 mg daily for ramipril. Doses may be higher in specific situations based on protocol and response. * **Heart Failure:** Initial doses are typically lower to assess tolerance. Common starting doses include: * Lisinopril: 5 mg orally once daily. * Enalapril: 2.5 mg orally once or twice daily. * Ramipril: 1.25 mg orally once daily. * Doses are titrated upwards based on tolerance and clinical response, aiming for target doses (e.g., lisinopril 32.5 mg/day, enalapril 10-20 mg BID, ramipril 5 mg BID) as tolerated. * **Post-MI:** Dosing varies by agent and timing of initiation. Generally started within 24 hours of MI in hemodynamically stable patients. * Captopril: 6.25 mg TID, titrated up to 50 mg TID. * Ramipril: 1.25 mg once daily, titrated up to 5 mg BID. * **Diabetic Nephropathy:** Dosing is similar to hypertension treatment, aiming for blood pressure control. ## Pediatric Dosing * **Hypertension:** Dosing is weight-based and varies by agent. * Enalapril: 0.07 to 0.1 mg/kg orally once daily, not to exceed 5 mg daily initially. Titrate up to a maximum of 0.5 mg/kg/day or 40 mg/day. * Lisinopril: 0.07 to 0.2 mg/kg orally once daily, not to exceed 10 mg daily. Titrate up to a maximum of 0.61 mg/kg/day or 40 mg/day. * Consult specific pediatric guidelines for other agents. ## Dose Adjustments * **Renal Impairment:** Reduce dose, especially in patients with creatinine clearance < 30 mL/min. Initial doses are often halved. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Use with caution; generally no dose adjustment needed for mild to moderate impairment, but may require lower starting doses and slower titration. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Concomitant use of aliskiren in patients with diabetes. * Pregnancy (especially second and third trimesters). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Less Common/Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in bilateral renal artery stenosis), rash, taste disturbances, neutropenia, elevated liver enzymes. ## Key Drug Interactions * **Potassium-sparing diuretics, Potassium supplements, Spironolactone, ARBs:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in elderly or volume-depleted patients. * **Diuretics:** Additive hypotensive effect. Risk of first-dose hypotension. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Concomitant use is contraindicated due to increased risk of angioedema. A washout period is required. ## Monitoring * **Blood Pressure:** Regularly, especially during initiation and dose titration. * **Renal Function:** Serum creatinine and BUN, particularly in patients with pre-existing renal disease, heart failure, or volume depletion. * **Serum Potassium:** Regularly, especially in patients with renal impairment, diabetes, or those taking potassium supplements/sparing diuretics. * **Signs of Angioedema:** Educate patients to report swelling of face, lips, tongue, or throat immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and typically resolves within 1-4 weeks after discontinuation. * First-dose hypotension can occur, especially in patients who are volume-depleted or on diuretics. Consider a lower starting dose and administer the first dose at bedtime or under close medical supervision. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Angioedema can occur at any time during therapy and is a medical emergency. * Consider alternative drug classes (e.g., ARBs) in patients who develop angioedema or cannot tolerate ACE inhibitors. *** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols for definitive guidance.