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## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications primarily used to manage 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 (systolic dysfunction) * Post-Myocardial Infarction (left ventricular dysfunction) * Diabetic Nephropathy (in patients with type 1 diabetes and proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically done every 1-2 weeks. * **Hypertension:** * Benazepril: Initial 10 mg once daily, usual range 20-40 mg/day, max 80 mg/day. * Captopril: Initial 12.5-25 mg BID-TID, usual range 25-150 mg BID, max 450 mg/day. * Enalapril: Initial 5 mg once daily, usual range 10-40 mg/day, max 40 mg/day. * Fosinopril: Initial 10 mg once daily, usual range 20-40 mg/day, max 80 mg/day. * Lisinopril: Initial 10 mg once daily, usual range 10-40 mg/day, max 80 mg/day. * Moexipril: Initial 7.5 mg once daily, usual range 15-30 mg/day, max 30 mg/day. * Perindopril: Initial 2.5-5 mg once daily, usual range 5-10 mg/day, max 10 mg/day. * Quinapril: Initial 10 mg BID, usual range 20-40 mg BID, max 80 mg/day. * Ramipril: Initial 2.5-5 mg once daily, usual range 10-20 mg/day, max 20 mg/day. * Trandolapril: Initial 0.5-1 mg once daily, usual range 1-4 mg/day, max 4 mg/day. * **Heart Failure:** * Enalapril: Initial 0.5 mg/kg/dose (max 2.5 mg) BID, titrate up to target doses (often 10 mg BID). * Captopril: Initial 6.25 mg TID, titrate up to target doses (often 50 mg TID). * Lisinopril: Initial 2.5-5 mg once daily, titrate up to target doses (often 20 mg once daily). * Ramipril: Initial 1.25-2.5 mg QD, titrate up to target doses (often 10 mg QD). * **Post-MI:** * Captopril: Initiated within 24 hours. 6.25 mg TID, then titrate. * Enalapril: 2.5 mg BID, then titrate. * Lisinopril: 5 mg QD, then titrate. * Ramipril: 1.25 mg QD, then titrate. * **Diabetic Nephropathy:** * Lisinopril: 10 mg once daily (can increase to 20 mg once daily if tolerated and needed). * Captopril: 25 mg TID (can increase to 50 mg TID if tolerated and needed). ## Pediatric Dosing Established dosing is available for some agents, often requiring careful titration and monitoring. Dosing varies significantly by age and weight. * **Hypertension:** * Enalapril: 6 months to < 16 years: 0.08 mg/kg/dose to 0.31 mg/kg/day divided BID. Max 40 mg/day. * Lisinopril: 6 to < 12 years: 0.07 to 0.2 mg/kg/day divided QD. Max 20 mg/day. * Ramipril: 5 to < 16 years: 1.25 mg QD, may increase to 2.5 mg QD. Max 5 mg/day. ## Dose Adjustments * **Renal Impairment:** * For most ACE inhibitors, starting doses should be reduced, and titration should be more cautious. Specific reductions are recommended based on creatinine clearance. * Example: Lisinopril: * CrCl 30-70 mL/min: Start 5 mg QD. * CrCl 10-30 mL/min: Start 2.5 mg QD. * CrCl < 10 mL/min: Start 2.5 mg QD, monitor closely. * **Hepatic Impairment:** Generally no dose adjustment needed, 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 mellitus or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Dry cough, dizziness, hyperkalemia, fatigue, hypotension. * **Serious:** Angioedema (including laryngeal edema, potentially fatal), acute kidney injury (especially in bilateral renal artery stenosis), hepatotoxicity, hyperkalemia, neutropenia, anaphylaxis. ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May attenuate the antihypertensive effect and increase the risk of renal dysfunction. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of hypotension. * **Lithium:** Increased lithium levels and toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs or Aliskiren:** Increased risk of adverse events like hyperkalemia and hypotension. Avoid in patients with diabetes. ## Monitoring * Blood pressure (at baseline and regularly). * Renal function (serum creatinine and BUN) at baseline and periodically. * Serum potassium at baseline and periodically, especially in patients with renal impairment or on potassium-sparing agents. * Signs and symptoms of angioedema. * Baseline CBC with differential for those at risk of neutropenia. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin. If cough is bothersome, consider switching to an ARB. * Angioedema can occur at any time during therapy and is a medical emergency. * ACE inhibitors are renoprotective in certain patients with diabetes and proteinuria. * Starting with a low dose and titrating slowly is crucial to minimize hypotension and other side effects. * Avoid in patients with bilateral renal artery stenosis due to risk of precipitating renal failure. *** *This information is intended for clinical use and does not substitute for professional medical advice. Always consult the most current prescribing information or a pharmacist for specific patient guidance.*