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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (to slow progression) * Proteinuric chronic kidney disease ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient tolerance. Common starting doses and maximum doses for frequently used agents include: * **Benazepril:** Start 10 mg once daily, titrate up to 40 mg once daily. * **Captopril:** Start 25 mg twice daily, titrate up to 50 mg three times daily. (Note: TID dosing is less common for other ACE inhibitors). * **Enalapril:** Start 2.5-5 mg once or twice daily, titrate up to 10-20 mg once or twice daily. Max 40 mg/day. * **Fosinopril:** Start 10 mg once daily, titrate up to 40 mg once daily. * **Lisinopril:** Start 10 mg once daily, titrate up to 40 mg once daily. * **Moexipril:** Start 7.5 mg once daily, titrate up to 30 mg once daily. * **Perindopril:** Start 2.5-5 mg once daily, titrate up to 10 mg once daily. * **Ramipril:** Start 2.5 mg once daily, titrate up to 10 mg once daily. * **Trandolapril:** Start 0.5-1 mg once daily, titrate up to 4 mg once daily. Dose titration is typically performed every 2-4 weeks based on blood pressure response and tolerability. ## Pediatric Dosing ACE inhibitors are generally not first-line agents for hypertension in pediatric patients unless specific indications exist (e.g., renovascular hypertension, significant proteinuria). Dosing is often weight-based and requires careful titration and monitoring. * **Enalapril:** 0.07-0.1 mg/kg/dose every 12-24 hours. Max dose depends on indication and age. * **Lisinopril:** 0.07-0.2 mg/kg/dose once daily. Max dose 20 mg/day in children < 6 years, 40 mg/day in children 6-12 years. Specific pediatric dosing guidelines should be consulted. ## Dose Adjustments * **Renal Impairment:** Dose reductions are often necessary for patients with significantly reduced renal function (CrCl < 30 mL/min). Consult specific drug monographs for detailed recommendations. * **Hepatic Impairment:** Generally do not require dose adjustment, but caution may be warranted. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (contraindicated due to risk of fetal injury and death). ## Adverse Effects Common adverse effects include: * Cough (dry, persistent) - estimated incidence 5-20% * Dizziness * Hypotension * Hyperkalemia * Fatigue * Rash * Angioedema (rare but potentially life-threatening) * Renal impairment (especially in patients with bilateral renal artery stenosis) ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride) and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Additive hypotensive effect. Risk of severe hypotension, especially with volume depletion. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **mTOR inhibitors (e.g., everolimus, sirolimus) and DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. * **ARBs:** Increased risk of hyperkalemia, angioedema, and hypotension. Avoid concurrent use unless carefully monitored in specific heart failure populations. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During treatment:** * Renal function (creatinine, BUN) within 1-2 weeks of initiation or dose increase, then periodically. * Serum potassium within 1-2 weeks of initiation or dose increase, then periodically. * Blood pressure regularly. * Monitor for signs and symptoms of angioedema. ## Clinical Pearls * The characteristic dry cough is usually reversible upon discontinuation. * Initiate at a low dose and titrate slowly, especially in the elderly, volume-depleted, or renally impaired patients, to minimize risk of hypotension and acute kidney injury. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Discontinue ACE inhibitors promptly if angioedema occurs. * Avoid in pregnancy. *** **Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and guidelines for complete details and to ensure patient safety.