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# Angiotensin-Converting Enzyme (ACE) Inhibitors ## Overview 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. This leads to vasodilation, decreased aldosterone secretion, and reduced sympathetic nervous system activity. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (left ventricular dysfunction) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (proteinuric) ## Adult Dosing * **Hypertension:** Initial doses vary by agent. Typical starting doses include: * Benazepril: 5-10 mg once daily * Captopril: 25 mg twice daily * Enalapril: 5 mg once daily * Fosinopril: 10 mg once daily * Lisinopril: 10 mg once daily * Moexipril: 7.5 mg once daily * Perindopril: 2.5-5 mg once daily * Quinapril: 5-10 mg twice daily * Ramipril: 2.5 mg once daily * Trandolapril: 1 mg once daily * **Titration:** Doses are typically titrated every 1-2 weeks based on blood pressure response. * **Maximum doses:** Vary by agent; commonly range from 40 mg daily for enalapril/lisinopril to 80 mg daily for quinapril. Consult specific agent guidelines. * **Heart Failure:** Initial doses are lower than for hypertension, with slower titration. Typical starting doses include: * Captopril: 6.25 mg three times daily * Enalapril: 2.5 mg twice daily * Lisinopril: 2.5-5 mg once daily * Ramipril: 1.25 mg once daily * **Titration:** Slowly titrated upwards over several weeks based on patient tolerance and clinical response. * **Maximum doses:** Vary by agent; commonly range from 10 mg three times daily for captopril to 40 mg daily for enalapril/lisinopril. * **Post-MI:** Initiated within 24 hours in hemodynamically stable patients. Dosing is similar to heart failure. * **Diabetic/Chronic Kidney Disease:** Dosing is based on hypertension or heart failure indications, with titration aimed at reducing proteinuria. ## Pediatric Dosing * **Hypertension:** Dosing varies significantly by age and agent. * **Captopril:** 0.3 mg/kg/dose orally every 8-12 hours. Maximum: 6 mg/kg/day. * **Enalapril:** 0.07 mg/kg/dose orally once daily. Maximum: 0.57 mg/kg/day. * **Lisinopril:** 0.07 mg/kg/dose orally once daily. Maximum: 0.61 mg/kg/day. * *Consult specific pediatric guidelines for other agents and weight-based dosing.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in moderate to severe impairment (CrCl < 30 mL/min). Refer to specific agent guidelines. * **Hepatic Impairment:** Use with caution; may require dose adjustment. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Concomitant use of sacubitril/valsartan. * Known hypersensitivity to ACE inhibitors. * Pregnancy (especially second and third trimesters). * Bilateral renal artery stenosis. ## Adverse Effects * **Common:** Dry cough, dizziness, headache, fatigue, hyperkalemia, rash. * **Serious:** Angioedema (potentially life-threatening), hypotension, renal failure, neutropenia/agranulocytosis (rare), hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Additive hypotensive effect; risk of first-dose hypotension. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **Mammalian target of rapamycin (mTOR) inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/valsartan:** Contraindicated due to increased angioedema risk. ## Monitoring * Blood pressure (prior to and following initiation/titration). * Serum potassium and creatinine (prior to initiation, within 1-2 weeks of initiation/titration, and periodically thereafter). * Signs and symptoms of angioedema. * Renal function (especially in patients with pre-existing renal disease or risk factors). ## Clinical Pearls * The characteristic dry cough is dose-independent and can occur weeks to months after initiation. Discontinuation usually resolves the cough. * Angioedema is a rare but severe adverse effect that requires immediate discontinuation of the ACE inhibitor and emergency management. * Hypotension, especially orthostatic hypotension, can occur, particularly with concurrent diuretic use or in volume-depleted patients. First-dose syncope is possible. * Monitor potassium closely, especially in patients with renal impairment, diabetes, or those taking potassium-sparing agents. * ACE inhibitors are generally considered safe and effective in pregnancy after the first trimester, but risks outweigh benefits. They are contraindicated in the second and third trimesters due to potential fetal harm. *** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details before making any treatment decisions.