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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, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart Failure (NYHA Class II-IV) * Left Ventricular Dysfunction post-Myocardial Infarction * Diabetic Nephropathy * Proteinuric Chronic Kidney Disease ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is generally recommended. * **Benazepril:** Hypertension: 5-40 mg once daily. Heart Failure: 2.5-40 mg once daily. * **Captopril:** Hypertension: 25-150 mg twice daily. Heart Failure: 6.25-150 mg three times daily. Post-MI: 6.25-12.5 mg three times daily. * **Enalapril:** Hypertension: 5-40 mg once or twice daily. Heart Failure: 2.5-40 mg once or twice daily. * **Fosinopril:** Hypertension: 10-40 mg once daily. Heart Failure: 5-40 mg once daily. * **Lisinopril:** Hypertension: 10-40 mg once daily. Heart Failure: 2.5-40 mg once daily. Post-MI: 5-40 mg once daily. * **Moexipril:** Hypertension: 7.5-30 mg once daily. * **Perindopril:** Hypertension: 2.5-10 mg once daily. Heart Failure: 2.5-10 mg once daily. * **Quinapril:** Hypertension: 10-80 mg once or twice daily. Heart Failure: 5-40 mg twice daily. * **Ramipril:** Hypertension: 2.5-20 mg once daily. Heart Failure: 2.5-10 mg once daily. Post-MI: 5-10 mg once daily. * **Trandolapril:** Hypertension: 1-4 mg once daily. Heart Failure: 1-4 mg once daily. Maximum doses vary by agent and indication. Always consult specific product labeling. ## Pediatric Dosing Dosing in pediatric patients is often based on weight and can vary significantly by age and indication. * **Enalapril:** Hypertension: 0.07-0.1 mg/kg/dose up to a maximum of 5 mg/dose initially, may titrate up to 0.57 mg/kg/day (max 40 mg/day) divided once or twice daily. * **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/day once daily (max 40 mg/day). * **Ramipril:** Hypertension: 0.05 mg/kg/day once daily (max 10 mg/day). Other ACE inhibitors may have established pediatric dosing; consult specific product information. ## Dose Adjustments * **Renal Impairment:** Reduce starting dose and titrate cautiously. Specific recommendations vary by drug and creatinine clearance. For significant renal impairment (e.g., CrCl < 30 mL/min), lower starting doses are typically used. * **Hepatic Impairment:** Use with caution. Captopril and enalapril are often preferred in mild to moderate hepatic impairment as they are not extensively metabolized by the liver. ## Contraindications * Hypersensitivity to the specific ACE inhibitor or any component of the formulation. * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment. * Second and third trimesters of pregnancy (Category D). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension, elevated serum creatinine. * **Less Common/Serious:** Angioedema (including laryngeal edema, potentially fatal), acute kidney injury, hepatic dysfunction, neutropenia, agranulocytosis (rare), Stevens-Johnson syndrome (rare), rash. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) & Potassium Supplements:** Increased risk of severe hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May reduce antihypertensive effect and increase risk of renal dysfunction, especially in volume-depleted patients or the elderly. * **Lithium:** ACE inhibitors can reduce lithium clearance, leading to increased serum lithium levels and toxicity. * **Diuretics:** Increased risk of hypotension, especially with initiating ACE inhibitor therapy in patients on diuretics. * **mTOR Inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of adverse events like hypotension, syncope, hyperkalemia, and renal dysfunction. Concomitant use is generally not recommended. * **Aliskiren:** Increased risk of adverse events such as hyperkalemia and hypotension; contraindicated in patients with diabetes or renal impairment. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, BUN, electrolytes (especially potassium). * **During therapy:** Blood pressure, serum creatinine, BUN, electrolytes (especially potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. Monitor for signs and symptoms of angioedema and cough. ## Clinical Pearls * The characteristic dry cough is dose-dependent and can occur months after initiation. If bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, elderly, or have renal insufficiency. * First-dose hypotension is a possibility, particularly in patients with heart failure or on diuretics. Advise patients to lie down if they experience dizziness. * ACE inhibitors are generally renoprotective in diabetic nephropathy and proteinuric chronic kidney disease. * Contraindicated in pregnancy due to potential fetal harm. *** *Disclaimer: This information is intended for healthcare professionals and should not replace a thorough review of the most current prescribing information, including product monographs and relevant clinical guidelines. Always verify drug information before prescribing.*