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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used primarily to treat cardiovascular conditions like hypertension and heart failure. 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 (especially reduced ejection fraction) * Post-myocardial infarction (for patients with clinical signs of heart failure or reduced ejection fraction) * Diabetic nephropathy (in patients with type 1 diabetes and proteinuria) * Chronic kidney disease (in select patients with proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Doses should be initiated low and titrated upwards. * **Hypertension:** Usual starting doses vary by agent (e.g., lisinopril 5-10 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 lower than for hypertension (e.g., lisinopril 5 mg daily, enalapril 2.5 mg twice daily, ramipril 1.25-2.5 mg daily). Titration to target doses is recommended (e.g., lisinopril 20 mg daily, enalapril 10 mg twice daily, ramipril 5 mg twice daily), guided by patient tolerability and clinical response. * **Post-MI:** Typically initiated within 24 hours if no contraindications exist. Dosing follows similar titration patterns as for heart failure. ## Pediatric Dosing ACE inhibitors are generally not first-line for pediatric hypertension unless specific comorbidities exist (e.g., renovascular hypertension, certain congenital heart diseases). Dosing varies significantly by age, weight, and indication. Consult pediatric-specific guidelines or resources. * **Enalapril:** Starting doses typically 0.07 mg/kg/day, may be increased up to 0.5 mg/kg/day. * **Lisinopril:** Starting doses typically 0.07 mg/kg/day, may be increased up to 0.61 mg/kg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Dosage adjustments are often necessary based on creatinine clearance. * **Hepatic Impairment:** Generally not recommended or require cautious use, as metabolism can be affected. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use of aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters). * Known hypersensitivity to ACE inhibitors. ## Adverse Effects * **Common:** Dry cough, dizziness, headache, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening, affecting face, lips, tongue, throat, intestines), acute kidney injury, rash, liver dysfunction. ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients. * **Diuretics (especially loop and thiazide):** Increased risk of symptomatic hypotension, particularly after the first dose. * **Lithium:** ACE inhibitors can increase serum lithium levels, leading to toxicity. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Concurrent use is generally contraindicated. * **mTOR inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. ## Monitoring * **Blood pressure:** Regularly monitor for efficacy and hypotension. * **Serum potassium:** Especially in patients with renal impairment, on potassium supplements, or potassium-sparing diuretics. * **Renal function (serum creatinine, BUN):** Monitor periodically, especially at initiation and dose increases, and in patients with pre-existing renal disease. * **Signs and symptoms of angioedema:** Educate patients to report immediately. ## Clinical Pearls * Angioedema can occur at any time during treatment, even after months or years of use, and is a medical emergency. * Cough is a common, dose-limiting side effect but is reversible upon discontinuation. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, salt-depleted, or have significant renal impairment. * Avoid in pregnancy due to risk of fetal injury or death. * Discontinue ACE inhibitors if angioedema occurs and never re-challenge. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety. Dosing and recommendations may vary based on specific patient factors and local protocols.