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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications that block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Myocardial Infarction (post-MI, especially with reduced ejection fraction or signs of heart failure) * Diabetic Nephropathy (especially in patients with proteinuria) * Chronic Kidney Disease (in select patients with proteinuria) ## Adult Dosing Dosing is highly individualized and dependent on the specific ACE inhibitor, indication, and patient response. Titration is typically guided by blood pressure and clinical signs/symptoms. * **Hypertension:** Starting doses vary widely. Common starting doses include: * Lisinopril: 10 mg orally once daily. Maximum: 40 mg/day. * Enalapril: 5 mg orally once or twice daily. Maximum: 40 mg/day. * Ramipril: 2.5 mg orally once daily. Maximum: 10 mg/day. * **Heart Failure:** Dosing often starts low and is titrated upward over weeks to months. * Enalapril: Starting dose 2.5 mg orally twice daily. Target dose often 10 mg orally twice daily. Maximum: 20 mg/day. * Ramipril: Starting dose 1.25 mg orally once daily. Target dose often 5 mg orally twice daily. Maximum: 10 mg/day. * **Post-Myocardial Infarction:** * Captopril: Starting dose 6.25 mg orally three times daily. Titrate up as tolerated. * Lisinopril: Starting dose 5 mg orally once daily. Titrate up as tolerated. ## Pediatric Dosing Dosing in pediatric patients is less standardized and often weight-based. It should be initiated by a specialist. * **Hypertension:** * Enalapril: 0.07 to 0.1 mg/kg orally once daily. Maximum: 0.5 mg/kg/day or 20 mg/day. * Lisinopril: 0.07 to 0.2 mg/kg orally once daily. Maximum: 0.61 mg/kg/day or 40 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly in patients with moderate to severe renal impairment. Specific adjustments vary by drug. * **Hepatic Impairment:** Generally less clear, but caution advised; may need lower starting doses. * **Volume Depletion:** Initiate at a lower dose or temporarily discontinue if hypotension or hypovolemia is present. * **Concomitant Diuretics:** Discontinue diuretic 2-3 days prior to initiating ACE inhibitor to reduce risk of hypotension, or start with a lower dose of the ACE inhibitor. ## Contraindications * History of angioedema related to ACE inhibitor therapy. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (CrCl < 60 mL/min). * Pregnancy (particularly in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening, especially involving the airway), hypotension, renal dysfunction/failure (especially in patients with bilateral renal artery stenosis), rash, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride), Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May reduce antihypertensive efficacy and increase risk of renal dysfunction, particularly in volume-depleted patients or those with pre-existing renal impairment. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to elevated serum lithium levels and toxicity. Monitor lithium levels closely. * **Diuretics:** Additive hypotensive effect. Risk of severe hypotension when initiating ACE inhibitor in patients taking diuretics. * **mTOR Inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Concurrent use with ACE inhibitors is contraindicated due to increased risk of angioedema. Separate administration by at least 36 hours. ## Monitoring * **Blood Pressure:** Regularly, especially after initiation and dose adjustments. * **Serum Creatinine and Potassium:** Baseline and periodically thereafter, especially in patients with renal impairment, heart failure, or those taking potassium-sparing agents or supplements. * **Renal Function:** Assess for evidence of renal impairment. * **Signs/Symptoms of Angioedema:** Patient education is crucial. ## Clinical Pearls * Cough is a common side effect and often resolves upon discontinuation. If persistent and bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * Initiate at low doses and titrate slowly, especially in patients with heart failure, renal impairment, or volume depletion, to minimize risk of hypotension and renal dysfunction. * Educate patients about the signs and symptoms of angioedema and to seek immediate medical attention if they occur. * Black box warning regarding fetal toxicity in pregnancy. Discontinue immediately if pregnancy is detected. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. *** *Disclaimer: This information is intended for clinical decision support and does not replace professional medical judgment. Always consult the most current prescribing information and relevant clinical guidelines before making therapeutic decisions.*