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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuria reduction) * Chronic kidney disease (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically guided by blood pressure and clinical signs of improvement. * **Hypertension:** Initial doses are low, with gradual increases every 1-2 weeks. For example: * Lisinopril: 10 mg orally once daily, titrate up to 40 mg once daily. * Enalapril: 5 mg orally once or twice daily, titrate up to 20 mg twice daily. * Ramipril: 2.5 mg orally once daily, titrate up to 10 mg once daily. * Maximum doses vary by agent and should not be exceeded without careful consideration. * **Heart Failure:** Dosing is often initiated at lower doses than for hypertension and titrated more slowly. For example: * Lisinopril: 5 mg orally once daily, titrate up to 40 mg once daily. * Enalapril: 2.5 mg orally twice daily, titrate up to 10-20 mg twice daily. * Ramipril: 1.25 mg orally once daily, titrate up to 10 mg once daily. * **Post-MI:** Typically initiated within 24 hours of MI in stable patients. For example: * Captopril: 6.25 mg orally three times daily, then titrate up to 12.5 mg three times daily, then 25 mg three times daily. * Lisinopril: 5 mg orally once daily, then 10 mg once daily, then 20 mg once daily. ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and heart failure. Dosing is weight-based and requires careful titration. * **Hypertension:** * Enalapril: 0.07 to 0.1 mg/kg/dose orally once daily, titrate up to 0.5 mg/kg/day. * Lisinopril: 0.07 to 0.2 mg/kg/day orally once daily, titrate up to 0.6 mg/kg/day (maximum 40 mg/day). * Dosing for other ACE inhibitors and specific indications in children may vary. ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary in patients with impaired renal function (CrCl < 30 mL/min). Initial doses should be lower, and titration should be more cautious. * **Hepatic Impairment:** Generally no dose adjustment is needed, but caution is advised. * **Volume Depletion/Hyponatremia:** Initiate at lower doses. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to ACE inhibitors. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, fatigue, hyperkalemia, headache. * **Serious:** Angioedema (facial, lip, tongue, glottis, extremities), acute kidney injury, severe hypotension, hepatotoxicity, agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of kidney damage, especially in volume-depleted patients. * **Diuretics (especially loop or thiazide):** Increased risk of symptomatic hypotension. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs, Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concurrent use in most patients, especially those with diabetes. ## Monitoring * **Blood Pressure:** Regularly monitor to assess efficacy and risk of hypotension. * **Serum Potassium:** Monitor at baseline, during dose titration, and periodically thereafter, especially in patients with renal impairment or those taking potassium-sparing agents. * **Renal Function (BUN, Creatinine):** Monitor at baseline and periodically. ACE inhibitors can cause a reversible increase in serum creatinine, particularly in patients with bilateral renal artery stenosis. * **Signs/Symptoms of Angioedema:** Educate patients to report immediately. ## Clinical Pearls * The characteristic dry cough is typically not associated with bronchospasm and often resolves upon discontinuation. * Initiate therapy at low doses and titrate slowly, especially in elderly patients, volume-depleted patients, and those with renal impairment. * Monitor for the first-dose hypotensive effect, particularly in patients on diuretics. Consider withholding diuretics for 2-3 days before initiating ACE inhibitor therapy or using a lower initial dose. * Avoid ACE inhibitors during pregnancy due to the risk of fetal harm. * ACE inhibitors can be renoprotective in patients with diabetes and proteinuria. --- *This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.*