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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used for treating hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure and cardiac workload. ## Primary Indications * Hypertension * Congestive Heart Failure (CHF) * Left Ventricular Dysfunction post-myocardial infarction * Diabetic Nephropathy (proteinuria reduction) * CKD with proteinuria (off-label in some guidelines) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically guided by blood pressure, heart rate, and signs/symptoms of the underlying condition. * **Hypertension:** Common starting doses vary. For example, lisinopril: 10 mg orally once daily. Target doses often range from 20-40 mg orally once daily. Maximum doses vary by agent (e.g., lisinopril up to 40 mg/day, ramipril up to 10 mg/day). * **Heart Failure:** Common starting doses are lower than for hypertension to avoid excessive hypotension. For example, enalapril: 2.5-5 mg orally twice daily. Target doses often range from 10-20 mg orally twice daily. Maximum doses vary by agent (e.g., enalapril up to 40 mg/day, ramipril up to 10 mg/day). * **Post-MI/Left Ventricular Dysfunction:** Similar to heart failure dosing, with gradual titration. * **Diabetic Nephropathy:** Often dosed to achieve maximal tolerated dose for blood pressure control while reducing proteinuria. ## Pediatric Dosing ACE inhibitor use in pediatrics is less established than in adults. Dosing should be based on specific guidelines or expert consultation. * **Hypertension:** Dosing varies significantly by age and weight. For example, enalapril: * Neonates/Infants: 0.1 mg/kg/dose every 12-24 hours. * Children: 0.08-0.3 mg/kg/day divided every 12-24 hours. * **Heart Failure:** Limited data, typically started at lower doses and titrated cautiously. ## Dose Adjustments * **Renal Impairment:** Dose reduction or slower titration is often necessary, especially in moderate to severe renal impairment. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. ## 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 (especially second and third trimesters; known teratogens). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in volume-depleted or renally compromised patients), hypotension, neutropenia/agranulocytosis (rare), elevated liver enzymes. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, trimethoprim:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive efficacy and increase risk of renal impairment, particularly in volume-depleted patients. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of hypotension and hypovolemia, particularly upon initiation of ACE inhibitor. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs, Aliskiren:** Increased risk of hyperkalemia and renal dysfunction; generally avoided, especially in specific populations (e.g., diabetes, CKD). ## Monitoring * **Blood Pressure:** Regularly, especially after dose initiation or titration. * **Serum Creatinine and Potassium:** Baseline and periodically during therapy, and more frequently with dose changes, renal impairment, or other risk factors for hyperkalemia. * **Renal Function:** Especially in patients with underlying renal disease, heart failure, or volume depletion. * **Signs/Symptoms:** Of angioedema, hypotension, hyperkalemia, and worsening heart failure. * **Complete Blood Count (CBC):** Periodically, especially in patients at risk for bone marrow suppression. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If troublesome, consider switching to an ARB. * Angioedema can occur at any time during therapy and requires immediate discontinuation of the ACE inhibitor. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted (e.g., recent diuretic use) or have heart failure, to minimize first-dose hypotension. * Monitor renal function and potassium closely, particularly in patients with bilateral renal artery stenosis or severe heart failure. * ACE inhibitors are generally contraindicated in pregnancy. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines for definitive patient management decisions.*