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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used 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 (systolic dysfunction) * Post-myocardial infarction (to reduce mortality and reinfarction) * Diabetic nephropathy (in patients with proteinuria) * Chronic kidney disease (in patients with proteinuria) ## Adult Dosing Dosing varies significantly by specific ACE inhibitor. Typical starting doses and maximum doses for common agents include: * **Benazepril:** Start at 5 mg once daily; titrate up to 20-40 mg once daily. * **Captopril:** Start at 6.25-12.5 mg TID; titrate up to 25-50 mg TID (max 150 mg/day). Note: Shorter half-life, often dosed TID. * **Enalapril:** Start at 2.5-5 mg once or twice daily; titrate up to 10-20 mg once or twice daily (max 40 mg/day). * **Enalaprilat (IV):** Start at 0.625 mg every 6 hours; titrate up to 1.25 mg every 6 hours (max 5 mg every 6 hours). * **Fosinopril:** Start at 10 mg once daily; titrate up to 20-40 mg once daily (max 80 mg/day). * **Lisinopril:** Start at 5-10 mg once daily; titrate up to 20-40 mg once daily (max 80 mg/day). * **Moexipril:** Start at 7.5 mg once daily; titrate up to 15-30 mg once daily (max 30 mg/day). * **Perindopril:** Start at 2.5-5 mg once daily; titrate up to 10 mg once daily (max 10 mg/day for hypertension, may be higher for heart failure). * **Quinapril:** Start at 5-10 mg twice daily; titrate up to 20-40 mg twice daily (max 80 mg/day). * **Ramipril:** Start at 2.5-5 mg once daily; titrate up to 10 mg once daily (max 10 mg/day). * **Trandolapril:** Start at 1 mg once daily; titrate up to 4 mg once daily (max 4 mg/day). **Note:** Initial doses are often lower in patients with heart failure, volume depletion, or renal impairment. Dose titration is based on clinical response and tolerability, typically every 1-2 weeks. ## Pediatric Dosing Dosing in pediatric patients is less standardized and often based on body weight. Specific recommendations vary by agent and indication. For hypertension, typical starting doses (mg/kg/day) include: * **Captopril:** 0.3-0.5 mg/kg/dose PO BID-TID. Max 1.5 mg/kg/day or 50 mg/day. * **Enalapril:** 0.07-0.1 mg/kg/dose PO QD-BID. Max 0.58 mg/kg/day or 20 mg/day. * **Lisinopril:** 0.07-0.2 mg/kg/dose PO QD. Max 0.61 mg/kg/day or 20 mg/day. **Note:** Pediatric dosing often requires careful titration and monitoring. Consultation with a pediatric specialist or pharmacist is recommended. ## Dose Adjustments * **Renal Impairment:** Dose reductions are typically necessary, especially in severe renal impairment (CrCl < 30 mL/min). Captopril and fosinopril may require less adjustment than other ACE inhibitors. Monitor serum creatinine and potassium. * **Hepatic Impairment:** Dose adjustments may be needed for agents with significant first-pass metabolism (e.g., enalapril, quinapril). ## 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 the second and third trimesters, due to risk of fetal harm). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, rash. * **Serious:** Angioedema (potentially life-threatening, especially involving the airway), hypotension, acute kidney injury (especially in bilateral renal artery stenosis), hyperkalemia, liver toxicity, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Diuretics (especially potassium-sparing):** Increased risk of hyperkalemia. * **Potassium supplements and Salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment; contraindicated in diabetes and renal impairment. * **Angiotensin II Receptor Blockers (ARBs):** Increased risk of hyperkalemia, hypotension, and renal impairment; generally avoid combination unless closely monitored. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. Monitor lithium levels. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, renal function (serum creatinine, BUN), serum potassium, urinalysis (especially for proteinuria). * **During Therapy:** * Blood pressure (especially after dose initiation or titration). * Renal function (serum creatinine, BUN) within 1-2 weeks of initiation/titration and periodically thereafter. * Serum potassium within 1-2 weeks of initiation/titration and periodically thereafter. * Monitor for signs and symptoms of angioedema, rash, and other adverse effects. ## Clinical Pearls * The characteristic dry cough is due to bradykinin accumulation and typically resolves within 1-4 weeks after discontinuation. * Angioedema can occur at any time during treatment and is a medical emergency. Discontinue ACE inhibitor immediately if suspected. * Initiate with low doses, especially in patients who are volume-depleted, elderly, or have renal impairment. * First-dose hypotension can occur, particularly in patients on diuretics or with heart failure. Advise patients to sit or lie down if they feel dizzy. * ACE inhibitors are generally considered safe and effective in pregnancy *before* the second trimester, but benefits must be weighed against risks. Avoid entirely in the second and third trimesters. * For patients with angioedema, substitution with an ARB may be considered, but cross-reactivity exists, and caution is advised. *** **Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information, product monographs, or relevant clinical guidelines for complete details and to ensure patient safety. Dosing may vary based on individual patient factors, local protocols, and specific clinical situations.