Ace%2525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that block the action of ACE, an enzyme that plays a role in regulating blood pressure. By inhibiting ACE, these drugs reduce the production of angiotensin II, a potent vasoconstrictor, and aldosterone, a hormone that promotes sodium and water retention. This leads to vasodilation and decreased fluid volume, lowering blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Acute myocardial infarction (post-MI) * Diabetic nephropathy * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is crucial. * **Hypertension:** Initial doses are typically low, with titration to efficacy and tolerability. Common starting doses include: * Lisinopril: 10 mg orally once daily. * Enalapril: 5 mg orally once or twice daily. * Ramipril: 2.5 mg orally once daily. * Benazepril: 10 mg orally once daily. Maximum doses vary by agent and indication but can range from 40 mg to 80 mg daily for some agents. * **Heart Failure:** Usually initiated at low doses and titrated up as tolerated, often aiming for target doses used in clinical trials. * Lisinopril: Target dose 32.5 mg orally once daily. * Enalapril: Target dose 10 mg orally twice daily. * Ramipril: Target dose 5 mg orally twice daily. * **Post-MI:** Typically initiated within 24 hours of symptom onset in hemodynamically stable patients. * Captopril: 6.25 mg orally three times daily, then titrated. * Enalapril: 2.5 mg orally twice daily, then titrated. * **Diabetic Nephropathy/CKD with Proteinuria:** Doses are titrated to achieve maximal reduction in proteinuria, typically up to the maximum recommended dose for hypertension or heart failure, depending on the agent. ## Pediatric Dosing Established pediatric dosing is available for some ACE inhibitors, typically for hypertension. Dosing is based on weight and requires careful titration. * **Enalapril:** 0.07 to 0.1 mg/kg orally once or twice daily, maximum 0.5 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07 to 0.2 mg/kg orally once daily, maximum 20 mg/day. Consult specific pediatric guidelines for precise dosing and available agents. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in severe renal impairment (CrCl <30 mL/min). Monitor potassium and creatinine closely. * **Hepatic Impairment:** Use with caution; reduced doses may be considered for some agents (e.g., enalapril). ## Contraindications * History of angioedema related to prior ACE inhibitor use. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, headache, fatigue, hyperkalemia. * **Serious:** Angioedema (can be life-threatening), acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), severe hypotension, hepatic dysfunction. ## Key Drug Interactions * **Potassium-sparing diuretics & Potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs & COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in elderly or volume-depleted patients. * **Diuretics (especially loop or thiazide):** Increased risk of symptomatic hypotension upon initiation, particularly with concomitant volume depletion. * **ARBs & Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid combination unless specifically indicated and closely monitored. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing risk of lithium toxicity. ## Monitoring * **Baseline:** Blood pressure, renal function (serum creatinine, BUN), electrolytes (especially potassium). * **During Therapy:** * Blood pressure: Regularly. * Renal function: Within 1-2 weeks of initiation or dose increase, then periodically. * Potassium: Within 1-2 weeks of initiation or dose increase, then periodically, especially in patients with renal impairment or on potassium-sparing agents. * Angioedema symptoms: Educate patients to report immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels and can occur days to months after initiation. If bothersome, consider switching to an ARB. * Angioedema is a medical emergency and can occur at any time, even after prolonged use. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. * Initiate at low doses and titrate slowly, especially in elderly patients, those with heart failure, or those taking diuretics. * Avoid in pregnancy due to risk of fetal harm. *** **Disclaimer:** This information is intended for healthcare professionals and is not a substitute for clinical judgment. Always consult the most current prescribing information, relevant guidelines, and patient-specific factors before making treatment decisions.