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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications that block the action of the angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. This results in decreased blood pressure and reduced workload on the heart. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Post-Myocardial Infarction (for patients with evidence of LV dysfunction or heart failure) * Diabetic Nephropathy (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient factors. Titration is typically guided by blood pressure response and tolerability. * **Hypertension:** Usual starting doses vary by agent (e.g., lisinopril 10 mg daily, enalapril 5 mg daily, ramipril 2.5 mg daily). Maximum doses also vary (e.g., lisinopril up to 40 mg daily, enalapril up to 40 mg daily, ramipril up to 10 mg daily). * **Heart Failure:** Usual starting doses are generally lower than for hypertension to minimize hypotension and renal dysfunction (e.g., lisinopril 2.5-5 mg daily, enalapril 2.5-5 mg daily, ramipril 1.25-2.5 mg daily). Doses are then titrated upwards based on tolerability and clinical response, with maximum doses varying by agent (e.g., lisinopril up to 35-40 mg daily, enalapril up to 20 mg daily, ramipril up to 10 mg daily). * **Post-MI:** Typically initiated within 24 hours in stable patients. Dosing regimens are similar to heart failure, with titration to target doses as tolerated. * **Diabetic Nephropathy:** Doses are often similar to those used for hypertension, aiming for blood pressure control and proteinuria reduction. ## Pediatric Dosing Dosing in pediatric patients is less established and should be guided by specialist recommendations or specific pediatric guidelines. Doses are typically weight-based and vary significantly by age and indication. Examples include: * **Hypertension:** Captopril: 0.5-1 mg/kg/day divided every 8-12 hours, max 4 mg/kg/day or 50 mg/day. Enalapril: 0.08 mg/kg/day divided every 12-24 hours, max 0.4 mg/kg/day or 40 mg/day. * **Heart Failure:** Dosing is generally initiated at the lower end of the hypertensive range and titrated cautiously. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary in patients with impaired renal function (CrCl < 30 mL/min). Initial doses may be halved, and subsequent titration should be guided by renal function and potassium levels. * **Hepatic Impairment:** Caution is advised; initial doses may need to be lower, although significant dose adjustments are not always required unless severe. * **Volume Depletion:** ACE inhibitors should be initiated at lower doses or temporarily discontinued in volume-depleted patients to prevent severe hypotension. ## Contraindications * 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 * Pregnancy (especially second and third trimesters) * Known hypersensitivity to the drug ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension, rash. * **Less Common/Serious:** Angioedema (facial, lip, tongue, glottis, extremities; life-threatening), acute kidney injury (especially in susceptible individuals), elevated liver enzymes, neutropenia, agranulocytosis (rare). ## Key Drug Interactions * **Diuretics:** Increased risk of hypotension and renal dysfunction. Potassium-sparing diuretics or potassium supplements can lead to severe hyperkalemia. * **NSAIDs:** Can reduce antihypertensive effect and increase risk of renal impairment, especially in elderly or dehydrated patients. * **Potassium Supplements & Potassium-Sparing Diuretics:** Increased risk of hyperkalemia. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR Inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. * **ARBs (Angiotensin II Receptor Blockers) & Aliskiren:** Increased risk of hypotension, hyperkalemia, and renal dysfunction. Avoid combination, especially in high-risk patients. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During therapy:** * Blood pressure (assess for symptomatic hypotension). * Serum creatinine and potassium within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Monitor for signs and symptoms of angioedema, especially after the first dose and with dose increases. ## Clinical Pearls * The characteristic dry cough is usually dose-dependent and often reversible upon discontinuation. * Initiate therapy at low doses and titrate slowly, especially in patients with heart failure, renal impairment, or volume depletion, to minimize hypotension and hyperkalemia. * ACE inhibitors are generally considered renal-protective in patients with proteinuria, particularly those with diabetes. * Discontinue ACE inhibitors immediately if angioedema occurs and manage appropriately. * Consider switching to an Angiotensin II Receptor Blocker (ARB) in patients who develop a persistent cough. *** *This information is intended for healthcare professionals and does not substitute for a thorough review of current prescribing information, local protocols, or individual patient assessment.*