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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of drugs 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 (MI) (in patients with LV dysfunction) * Diabetic nephropathy (in patients with type 2 diabetes and hypertension) * Chronic kidney disease (CKD) (in patients with hypertension and proteinuria) ## Adult Dosing Dosing varies significantly by agent and indication. Titration is typically guided by blood pressure response and tolerability. * **Hypertension:** Initial doses are low and titrated every 2-4 weeks. Examples include: * Lisinopril: Start 10 mg PO daily, titrate up to 40 mg PO daily. * Enalapril: Start 5 mg PO daily or BID, titrate up to 40 mg PO daily. * Ramipril: Start 2.5 mg PO daily, titrate up to 10 mg PO daily. * **Heart Failure:** Typically initiated at a low dose and titrated upwards over weeks to months as tolerated. Examples: * Lisinopril: Start 5 mg PO daily, target 10-40 mg PO daily. * Enalapril: Start 2.5-5 mg PO BID, target 10-20 mg PO BID. * Ramipril: Start 1.25-2.5 mg PO BID, target 5 mg PO BID. * **Post-MI:** Start 5 mg PO daily, target 10 mg PO daily. Maximum doses are agent-specific and should not be exceeded without careful consideration of benefit versus risk. ## Pediatric Dosing ACE inhibitor dosing in pediatrics is less standardized and often requires specialist consultation. * **Hypertension:** Dosing is based on body weight and varies by agent. * Enalapril: 0.07-0.1 mg/kg/day PO divided BID, maximum 0.5 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/day PO once daily, maximum 20 mg/day (for age 6-12 years). ## Dose Adjustments * **Renal Impairment:** Dose reductions are generally required for patients with significant renal impairment (CrCl < 30 mL/min). Specific reductions vary by agent. * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. ## Contraindications * History of angioedema related to ACE inhibitor therapy * 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, hyperkalemia, fatigue, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, severe hypotension, hyperkalemia. ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Angiotensin II Receptor Blockers (ARBs), Aliskiren:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 Inhibitors:** May blunt the antihypertensive effect and increase the risk of kidney damage, especially in volume-depleted patients. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **Lithium:** ACE inhibitors can reduce lithium clearance, leading to lithium toxicity. ## Monitoring * **Blood Pressure:** Regularly monitor blood pressure, especially after initiation or dose adjustments. * **Renal Function:** Monitor serum creatinine and BUN at baseline and periodically thereafter, especially in patients with pre-existing renal disease or heart failure. * **Serum Potassium:** Monitor serum potassium at baseline and periodically, especially in patients with renal impairment or those taking potassium-sparing agents. * **Angioedema:** Educate patients on the signs and symptoms and to seek immediate medical attention if they occur. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an ARB. * Initiate at low doses and titrate slowly, particularly in patients who are volume-depleted, salt-depleted, or have heart failure. * ACE inhibitors are generally considered renoprotective in diabetic patients with proteinuria. * If angioedema occurs, discontinue the ACE inhibitor immediately and never re-challenge the patient. *** *This information is intended for clinical use and is not a substitute for professional medical advice. Always consult current prescribing information and local protocols for the most up-to-date guidance.*