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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs used to treat hypertension and heart failure. They work by blocking the production of angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart Failure (HF) with reduced ejection fraction (HFrEF) * Left ventricular dysfunction post-myocardial infarction (MI) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing * **Hypertension:** Initial doses vary by agent. Typical starting doses: * Benazepril: 10 mg once daily. * Captopril: 25 mg twice daily. * Enalapril: 5 mg once daily. * Lisinopril: 10 mg once daily. * Ramipril: 2.5 mg once daily. * Titration is guided by blood pressure response. Maximum doses vary by agent and indication, often ranging from 20-40 mg daily for most agents in hypertension. * **Heart Failure:** Initial doses are typically lower than for hypertension. * Captopril: 6.25 mg three times daily. * Enalapril: 2.5 mg once or twice daily. * Lisinopril: 5 mg once daily. * Ramipril: 1.25 mg once daily. * Titration is guided by blood pressure, renal function, and potassium levels. Target doses are often higher than initial doses. * **Post-MI:** Typically initiated within 24 hours in hemodynamically stable patients. * Enalapril: 2.5 mg twice daily. * Lisinopril: 5 mg once daily. * Ramipril: 1.25 mg once daily. * Titration guided by blood pressure and tolerability. ## Pediatric Dosing * **Hypertension:** Dosing varies by age and indication. * Enalapril: 0.07 to 0.2 mg/kg/day divided every 12-24 hours. * Lisinopril: 0.07 to 0.2 mg/kg/day once daily. * Maximum doses for pediatric patients vary by agent and are generally lower than adult maximums. Specific protocols should be consulted. ## Dose Adjustments * **Renal Impairment:** Dose reductions are typically necessary in patients with renal insufficiency (CrCl < 30 mL/min). Consult specific agent guidelines for precise adjustments. * **Hepatic Impairment:** Captopril and Enalapril may require dose reduction due to reduced metabolism. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters; Category C in 1st trimester). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (can be life-threatening), acute kidney injury (especially in patients with bilateral renal artery stenosis), hypotension, neutropenia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive efficacy and increase risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Contraindicated in patients with diabetes. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal impairment. Not recommended for routine coadministration. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. ## Monitoring * Blood pressure. * Serum creatinine and BUN (especially at initiation and with dose changes). * Serum potassium (especially in patients with renal impairment, diabetes, or concurrent use of potassium-sparing agents). * Signs and symptoms of angioedema. * Complete blood count (CBC) periodically, especially in patients at risk for neutropenia. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * ACE inhibitors are generally considered renoprotective in diabetic patients with proteinuria. * Initiation in elderly patients or those with volume depletion may require lower starting doses to avoid excessive hypotension. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor and appropriate management. *** **Disclaimer:** This information is intended for clinical use and does not replace a comprehensive review of current prescribing information, clinical guidelines, or consultation with a specialist. Always verify current drug information before prescribing.