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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat cardiovascular conditions. 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) * Acute myocardial infarction (post-MI) * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing varies significantly by specific ACE inhibitor. A general approach is to start at a low dose and titrate upwards based on patient response and tolerability. * **Hypertension:** Typical starting doses are low (e.g., lisinopril 5 mg daily, enalapril 2.5-5 mg daily, ramipril 2.5 mg daily). Maintenance doses vary (e.g., lisinopril 10-40 mg daily, enalapril 10-40 mg daily, ramipril 5-10 mg daily). * **Heart Failure:** Dosing often starts lower than for hypertension and is titrated more slowly (e.g., lisinopril 2.5-5 mg daily, enalapril 2.5-5 mg twice daily, ramipril 1.25-2.5 mg daily). Target doses depend on the specific agent and patient tolerance but aim for doses shown in clinical trials to improve outcomes. * **Post-MI:** Initiated within 24 hours in hemodynamically stable patients (e.g., captopril 6.25 mg TID, ramipril 1.25-2.5 mg BID). * **Diabetic Nephropathy:** Dosing is similar to hypertension, aiming for blood pressure control and proteinuria reduction. ## Pediatric Dosing ACE inhibitor dosing in pediatrics is less standardized and often based on weight. * **Hypertension:** * Enalapril: 0.05-0.2 mg/kg/dose orally every 12-24 hours (max 0.5 mg/kg/day or 40 mg/day). * Lisinopril: 0.07-0.2 mg/kg/dose orally once daily (max 20 mg/day). * Captopril: 0.3-0.5 mg/kg/dose orally every 8 hours. * **Heart Failure:** Dosing is typically initiated at the lower end of the hypertension range and titrated cautiously. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific adjustments depend on the agent and the degree of renal impairment (e.g., creatinine clearance). * **Hepatic Impairment:** Some agents may require dose adjustment, particularly those undergoing hepatic metabolism. ## Contraindications * History of angioedema related to prior ACE inhibitor therapy. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters, Category X in 1st trimester). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in those with bilateral renal artery stenosis), rash, dysgeusia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (thiazide or loop):** Increased risk of symptomatic hypotension. * **Lithium:** ACE inhibitors may reduce lithium clearance, leading to lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Concurrent use is contraindicated due to increased angioedema risk. Allow a 36-hour washout period after stopping an ACE inhibitor before starting sacubitril/valsartan, and vice versa. ## Monitoring * **Baseline and periodically:** Serum potassium, serum creatinine, BUN. * **With initiation and dose changes:** Blood pressure. * **As clinically indicated:** Complete blood count (CBC) if risk factors for neutropenia exist. ## Clinical Pearls * The characteristic dry cough is due to increased bradykinin levels. Switching to an angiotensin II receptor blocker (ARB) is often effective for this side effect. * Hypotension is more likely in patients who are volume-depleted or on concomitant diuretic therapy. Consider a lower starting dose or withholding diuretics prior to initiation. * Angioedema can occur at any time during therapy and requires immediate discontinuation of the ACE inhibitor. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. * Avoid in patients with bilateral renal artery stenosis due to the risk of severe renal impairment. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for definitive guidance. Drug dosing and management can vary based on individual patient factors and local protocols.