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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that primarily treat hypertension and heart failure. They work by blocking 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 (NYHA Class II-IV) * Left Ventricular Dysfunction (post-myocardial infarction) * Diabetic Nephropathy * Renal Impairment in patients with diabetes and hypertension ## Adult Dosing Dosing varies significantly by specific ACE inhibitor and indication. Common starting doses are typically low and titrated upwards. * **Hypertension:** Dosing is highly individualized. Examples: * Lisinopril: Start at 5-10 mg once daily, titrate up to a maximum of 40 mg once daily. * Enalapril: Start at 5 mg once or twice daily, titrate up to a maximum of 40 mg once daily (or 20 mg twice daily). * Ramipril: Start at 2.5 mg once daily, titrate up to a maximum of 10 mg once daily. * **Heart Failure:** * Enalapril: Start at 2.5 mg twice daily, titrate up to a maximum of 20 mg twice daily. * Lisinopril: Start at 5 mg once daily, titrate up to a maximum of 40 mg once daily. * **Post-MI:** * Ramipril: Start at 2.5 mg twice daily, titrate up to a maximum of 10 mg twice daily. ## Pediatric Dosing Dosing in pediatric patients is not as well-established and is often based on weight. * **Hypertension:** Dosing varies by agent and age. For example: * Enalapril: 0.07 mg/kg/day to 0.38 mg/kg/day (max 40 mg/day). Specific recommendations may differ based on age group. ## Dose Adjustments * **Renal Impairment:** Initial doses should be lower, and titration should be more gradual. Significant dose reduction may be necessary in severe renal impairment (CrCl < 30 mL/min). * **Hepatic Impairment:** Generally no dose adjustment needed, but caution advised due to potential for hepatic reactions. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with 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. * **Serious:** Angioedema (face, lips, tongue, throat, extremities, intestines), acute kidney injury, hepatotoxicity, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, especially in patients with pre-existing renal disease. * **Lithium:** Increased lithium levels and risk of toxicity. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension, particularly after initiating ACE inhibitor therapy. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., vildagliptin):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor for efficacy and hypotension. * **Renal Function:** Baseline and periodic monitoring of serum creatinine and BUN. * **Electrolytes:** Baseline and periodic monitoring of serum potassium, especially in patients with renal impairment or those taking potassium-sparing agents. * **Angioedema:** Educate patients to report any signs immediately. * **Cough:** Assess for persistent cough. ## Clinical Pearls * Initiate at a low dose and titrate slowly to minimize hypotension and cough. * Advise patients about the potential for a dry cough and angioedema, and to seek immediate medical attention if symptoms occur. * ACE inhibitors are generally considered safe and effective in diabetic patients, offering renal protective benefits. * Discontinue immediately if angioedema occurs. * ACE inhibitors are contraindicated in pregnancy. *** **Disclaimer:** This information is intended for clinical use and does not replace professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete details, including contraindications, warnings, and precautions, before making any treatment decisions.