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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications that block the production of angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. They also decrease aldosterone secretion, promoting sodium and water excretion. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI patients with evidence of LV dysfunction or heart failure) * Diabetic nephropathy (proteinuria) * Chronic kidney disease (non-diabetic, proteinuria) ## Adult Dosing Dosing is highly individualized and titrate to blood pressure and clinical response. Specific starting doses and titration schedules may vary based on local protocols and patient characteristics. * **Benazepril:** Start 5-10 mg once daily. Max 40 mg once daily. * **Captopril:** Start 12.5-25 mg twice daily. Max 150 mg three times daily. * **Enalapril:** Start 2.5-5 mg once daily. Max 40 mg once daily (oral). Max 5 mg IV q6h (IV). * **Fosinopril:** Start 10 mg once daily. Max 80 mg once daily. * **Lisinopril:** Start 5-10 mg once daily. Max 40 mg once daily. * **Moexipril:** Start 7.5 mg once daily. Max 30 mg once daily. * **Perindopril:** Start 2.5-5 mg once daily. Max 10 mg once daily. * **Quinapril:** Start 5-10 mg twice daily. Max 80 mg twice daily. * **Ramipril:** Start 2.5-5 mg once daily. Max 20 mg once daily. * **Trandolapril:** Start 0.5-1 mg once daily. Max 4 mg once daily. ## Pediatric Dosing ACE inhibitors are generally not first-line agents in pediatric hypertension, but may be used in specific situations. Dosing is less standardized and relies heavily on clinical judgment and monitoring. * **Enalapril:** 0.07-0.1 mg/kg/dose orally once daily, titrate up to 0.57 mg/kg/day divided once or twice daily. Max 40 mg/day. * **Captopril:** 0.3 mg/kg/dose orally three times daily. Max 150 mg/day. * **Lisinopril:** 0.07-0.2 mg/kg/dose orally once daily. Max 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. For lisinopril, if CrCl < 30 mL/min, start 5 mg once daily. * **Hepatic Impairment:** Captopril and enalapril (prodrugs) may require dose reduction. Fosinopril is not extensively metabolized by the liver and may be preferred. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Pregnancy (teratogenic, especially in the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (potentially life-threatening), hypotension, acute kidney injury, elevated liver enzymes, agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May increase blood pressure and reduce antihypertensive effect; increased risk of renal impairment. * **Diuretics (especially loop or thiazide):** Increased risk of hypotension, especially after the first dose. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid in patients with diabetes or renal impairment. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Generally avoid coadministration. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing risk of lithium toxicity. ## Monitoring * **Blood Pressure:** Regularly, especially during titration. * **Renal Function (Serum Creatinine, BUN):** Baseline and periodically, especially in patients with pre-existing renal disease or at risk. * **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment, hyperkalemia risk factors, or those on potassium-sparing agents. * **Angioedema:** Educate patients on signs and symptoms and advise prompt discontinuation and medical attention if they occur. ## Clinical Pearls * ACE inhibitors are effective in reducing proteinuria in diabetic and non-diabetic kidney disease. * The characteristic dry cough is thought to be due to bradykinin accumulation and is usually reversible upon discontinuation. * Hypotension is more likely with the first dose, in volume-depleted patients, or those on diuretics. Consider a lower starting dose or withholding diuretics prior to initiation. * Angioedema is a rare but serious adverse effect that can occur at any time during treatment. Discontinue immediately if suspected. * Do not use in pregnancy. Counsel patients of childbearing potential. *** *This information is intended for clinical decision-making and should not replace a thorough review of the most current prescribing information and relevant literature. Always verify current drug information before prescribing.*