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# Angiotensin-Converting Enzyme (ACE) Inhibitors ## Overview ACE inhibitors are a class of medications that block the action of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. This results in decreased blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI management) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically guided by blood pressure and clinical status. * **Hypertension:** Initial doses vary by agent, often starting low and titrating upwards. Maximum doses are also agent-specific. * *Examples:* * Lisinopril: Start 10 mg once daily, titrate to 20-40 mg once daily. Max 80 mg/day. * Enalapril: Start 5 mg once or twice daily, titrate to 10-20 mg once or twice daily. Max 40 mg/day. * Ramipril: Start 2.5 mg once daily, titrate to 5-10 mg once daily. Max 10 mg/day. * **Heart Failure:** Often initiated at a lower dose than for hypertension and titrated more slowly. * *Examples:* * Enalapril: Start 2.5 mg twice daily, titrate to 10-20 mg twice daily. Max 20 mg/day. * Ramipril: Start 1.25-2.5 mg twice daily, titrate to 5 mg twice daily. Max 10 mg/day. * **Post-MI:** Started within 24 hours in hemodynamically stable patients. * *Examples:* * Captopril: Start 6.25 mg three times daily, titrate to target dose. * Lisinopril: Start 5 mg once daily, titrate to 10 mg once daily. * **Diabetic Nephropathy:** Doses are typically similar to those used for hypertension, aiming for optimal blood pressure control and proteinuria reduction. ## Pediatric Dosing Dosing in children is less established and often based on weight. Specific protocols may vary. * **Hypertension:** * *Examples:* * Enalapril: 0.07-0.1 mg/kg/dose every 12-24 hours. Max 0.5 mg/kg/day. * Lisinopril: 0.07-0.2 mg/kg/dose once daily. Max 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in patients with significant renal dysfunction. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Use with caution; initial doses may need to be reduced. * **Volume Depletion:** Correct volume depletion before initiating therapy to avoid hypotension. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use of sacubitril/valsartan (within 36 hours of the last dose of sacubitril/valsartan). * Pregnancy (teratogenic effects). * Bilateral renal artery stenosis. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue. * **Serious:** Angioedema (including laryngeal edema), acute kidney injury, hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, Potassium supplements, Salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **Lithium:** Increased lithium levels and risk of toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., vildagliptin):** Increased risk of angioedema. ## Monitoring * Blood pressure regularly. * Serum creatinine and electrolytes (especially potassium) within the first few weeks of therapy and periodically thereafter. * Renal function in patients with risk factors. * Signs and symptoms of angioedema. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and typically resolves upon discontinuation. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, on diuretics, or have renal impairment. * Black patients and those with low renin hypertension may have a less pronounced response to ACE inhibitors; consider alternative or add-on therapy. * Discontinue immediately if angioedema occurs. *** This information is intended for clinical use and does not replace the need to consult official prescribing information and relevant clinical guidelines. Always verify current dosing and safety information with the most up-to-date resources before prescribing.