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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. 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 (systolic dysfunction) * Left Ventricular Dysfunction post-Myocardial Infarction * Diabetic Nephropathy (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is often required. * **Lisinopril:** * Hypertension: Start at 5-10 mg orally once daily, titrate to 20-40 mg once daily. Max: 40 mg/day. * Heart Failure: Start at 2.5-5 mg orally once daily, titrate to 10-20 mg once daily. Max: 40 mg/day. * **Enalapril:** * Hypertension: Start at 5 mg orally once or twice daily, titrate to 10-20 mg once or twice daily. Max: 40 mg/day. * Heart Failure: Start at 2.5 mg orally once or twice daily, titrate to 10-20 mg once or twice daily. Max: 40 mg/day. * **Ramipril:** * Hypertension: Start at 2.5 mg orally once daily, titrate to 10 mg once daily. Max: 10 mg/day. * Heart Failure: Start at 1.25 mg orally once daily, titrate to 5 mg twice daily. Max: 10 mg/day. * **Benazepril:** * Hypertension: Start at 5-10 mg orally once daily, titrate to 20-40 mg once daily. Max: 40 mg/day. * **Captopril:** * Hypertension: Start at 12.5 mg orally twice or three times daily, titrate to 25-50 mg twice or three times daily. Max: 150 mg three times daily. * Heart Failure: Start at 6.25 mg orally three times daily, titrate to 12.5-25 mg three times daily. Max: 150 mg three times daily. Specific initial and target doses may vary based on local protocols and patient-specific factors. ## Pediatric Dosing ACE inhibitors are generally not first-line agents for pediatric hypertension unless specific comorbidities exist. Dosing is highly variable. * **Lisinopril:** * Hypertension (1 month to 16 years): Start at 0.07 mg/kg orally once daily (max 5 mg). Titrate up to a maximum of 0.61 mg/kg/day (max 40 mg/day). * **Enalapril:** * Hypertension (1 month to 16 years): Start at 0.07 mg/kg orally once daily (max 5 mg). Titrate up to a maximum of 0.58 mg/kg/day (max 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally recommended, especially for patients with significant renal insufficiency. Consult specific drug monographs for detailed adjustments. * **Hepatic Impairment:** Cautious use; dose adjustments may be necessary. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes. * Second and third trimesters of pregnancy. ## Adverse Effects * **Common:** Dry cough, dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (facial, laryngeal, intestinal), acute kidney injury, hepatotoxicity, neutropenia, hyperkalemia. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) & Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs & COX-2 Inhibitors:** May attenuate antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially thiazides):** Additive hypotensive effect. Risk of hypovolemia and subsequent acute kidney injury. * **Lithium:** Increased lithium levels and risk of toxicity. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Avoid concomitant use; increased risk of angioedema. ## Monitoring * **Baseline:** Renal function (creatinine, BUN), potassium levels, blood pressure. * **During Therapy:** Renal function, potassium levels, blood pressure. Monitor for signs and symptoms of angioedema, hypersensitivity, and hypotension. ## Clinical Pearls * Dry cough is a common, often dose-limiting, side effect. If severe, consider switching to an Angiotensin II Receptor Blocker (ARB). * First-dose hypotension can occur, particularly in patients who are volume-depleted or on diuretics. * Angioedema is a medical emergency and can occur at any time during therapy. Discontinue ACE inhibitor immediately if angioedema is suspected. * Use with caution in patients with bilateral renal artery stenosis due to the risk of acute kidney injury. * ACE inhibitors are generally safe and effective in pregnancy during the first trimester, but should be avoided in the second and third trimesters due to teratogenic risks. *** *Disclaimer: 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. Drug information can change, and individual patient needs must be considered.*