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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications used primarily for cardiovascular conditions. 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 (HF) with reduced ejection fraction (HFrEF) * Myocardial Infarction (MI) - post-MI patients with evidence of LV dysfunction * Diabetic nephropathy ## Adult Dosing Dosing is highly individualized based on the specific ACE inhibitor, indication, and patient response. Common starting doses are typically low and titrated upwards. Examples include: * **Lisinopril:** * Hypertension: Start at 5-10 mg once daily. Titrate to 10-40 mg once daily. Max: 40 mg/day. * HFrEF: Start at 5 mg once daily. Titrate to 5-35 mg once daily. Max: 35 mg/day. * Post-MI: Start at 5 mg once daily, with additional doses of 5 mg on days 2 and 3, then 10 mg once daily thereafter. Max: 10 mg/day. * **Ramipril:** * Hypertension: Start at 2.5 mg once daily. Titrate to 5-10 mg once daily. Max: 10 mg/day. * HFrEF: Start at 1.25 mg once daily. Titrate to 5-10 mg once daily. Max: 10 mg/day. * Post-MI: Start at 1.25 mg once daily. Titrate to 2.5-5 mg twice daily. Max: 10 mg/day. Consult specific drug monographs for exact dosing guidelines for all ACE inhibitors. ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and heart failure. Dosing varies significantly by age and indication. * **Enalapril:** * Hypertension: 0.07-0.1 mg/kg/day divided into two doses, not to exceed 0.5 mg/kg/day or 40 mg/day. * **Lisinopril:** * Hypertension: 0.07-0.2 mg/kg/day once daily, not to exceed 20 mg/day. There is significant variability and less established data in pediatric populations compared to adults. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific guidelines vary by ACE inhibitor and degree of renal impairment (e.g., CrCl < 30 mL/min). * **Hepatic Impairment:** No specific dose adjustment is typically required, but caution is advised. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or moderate to severe renal impairment. * Pregnancy (especially second and third trimesters). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), hyperkalemia, dizziness, hypotension, headache, fatigue, renal impairment. * **Serious:** Angioedema (including laryngeal edema), severe hypotension, acute kidney injury, hyperkalemia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics & Potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction, especially in elderly or volume-depleted patients. * **Diuretics (especially potassium-wasting):** Increased risk of hypotension, especially with initial doses. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. Do not co-administer; allow at least 36 hours after stopping sacubitril/valsartan before initiating an ACE inhibitor. ## Monitoring * **Renal function (serum creatinine and BUN)** * **Serum potassium** * **Blood pressure** * **Signs and symptoms of angioedema** ## Clinical Pearls * Cough is a common, often dose-limiting side effect. If cough occurs and is bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, elderly, or have renal impairment. * First-dose hypotension is a risk, particularly in patients on diuretics. Consider withholding diuretics for 2-3 days prior to initiating ACE inhibitor therapy. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. *** **Disclaimer:** This information is intended for educational purposes only and does not constitute medical advice. Always verify current prescribing information with official drug monographs and consult with a healthcare professional for patient-specific treatment decisions.