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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of drugs used primarily for the management of cardiovascular conditions, including hypertension, heart failure, and post-myocardial infarction. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Left Ventricular Dysfunction (post-myocardial infarction) * Diabetic Nephropathy (proteinuria reduction) ## Adult Dosing Dosing varies by specific agent and indication. Titration is typically guided by patient response and tolerability. Examples: * **Hypertension:** * Benazepril: 10-40 mg once daily. Max: 80 mg daily. * Captopril: 25 mg two to three times daily. Max: 150 mg three times daily. * Enalapril: 10-40 mg once daily or 5-20 mg twice daily. Max: 40 mg daily. * Lisinopril: 10-40 mg once daily. Max: 80 mg daily. * Ramipril: 2.5-5 mg once daily. Max: 20 mg daily. * **Heart Failure:** * Enalapril: 2.5-20 mg twice daily. Max: 40 mg daily. * Lisinopril: 5-20 mg once daily. Max: 35 mg daily. * Ramipril: 1.25-5 mg twice daily. Max: 10 mg daily. * **Post-MI:** * Captopril: 6.25 mg three times daily, titrating up to 50 mg three times daily. * Enalapril: 5 mg once or twice daily, titrating up to 10 mg twice daily. * Lisinopril: 5 mg once daily, titrating up to 10 mg once daily. ## Pediatric Dosing Established pediatric dosing is available for some agents, typically for hypertension. Dosing is weight-based and requires careful titration. * **Enalapril:** 0.07-0.1 mg/kg/dose orally once or twice daily. Max: 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07-0.2 mg/kg/dose orally once daily. Max: 20 mg/day. * **Ramipril:** 0.05 mg/kg/dose orally once daily. Max: 2.5 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Specific recommendations vary by agent and GFR. For example, in severe renal impairment (CrCl < 30 mL/min), enalapril starting dose is typically 5 mg daily. * **Hepatic Impairment:** Use with caution; may require dose reduction. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters). ## Adverse Effects * Cough (dry, persistent) * Hypotension (especially with first dose or volume depletion) * Hyperkalemia * Angioedema (rare but serious, can occur at any time) * Dizziness, fatigue * Renal dysfunction (especially in patients with bilateral renal artery stenosis) * Rash ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) & Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension. * **Lithium:** May increase lithium levels and toxicity. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of adverse effects, particularly hyperkalemia and hypotension; generally avoided. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. ## Monitoring * Blood pressure (before and after initiation/titration) * Serum potassium levels (baseline and periodically, especially in patients with renal impairment or on potassium-sparing agents) * Renal function (serum creatinine and BUN, baseline and periodically) * Signs and symptoms of angioedema and cough ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. * First-dose hypotension is more likely in patients who are salt-depleted or on diuretics. Consider holding diuretics before starting ACE inhibitor therapy. * Angioedema is a medical emergency. Discontinue the ACE inhibitor immediately if suspected. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Discontinue ACE inhibitors if significant hyperkalemia or worsening renal function occurs. * Always consider the specific agent's pharmacokinetic and pharmacodynamic properties when selecting and dosing. Please consult the most current prescribing information for definitive dosing, contraindications, and interactions. *** **Disclaimer:** This information is for educational purposes only and does not substitute for professional medical advice. Always verify current prescribing information and guidelines with official sources before making clinical decisions.