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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications used primarily 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 (especially with reduced ejection fraction) * Post-myocardial infarction (to reduce mortality and prevent remodeling) * Diabetic nephropathy (to slow progression) * Proteinuric kidney disease ## Adult Dosing Dosing varies significantly by agent. Typical starting doses for common agents include: * **Lisinopril:** 10 mg orally once daily. Maximum: 40 mg orally once daily. * **Enalapril:** 5 mg orally once or twice daily. Maximum: 20 mg orally twice daily. * **Ramipril:** 2.5 mg orally once daily. Maximum: 10 mg orally once daily. * **Benazepril:** 10 mg orally once daily. Maximum: 40 mg orally once daily. * **Captopril:** 25 mg orally two or three times daily. Maximum: 150 mg orally three times daily. (Note: Shorter half-life, requires more frequent dosing) Individual titration based on blood pressure response and tolerability is standard. ## Pediatric Dosing * **Hypertension:** Dosing varies by agent and age. For example: * **Enalapril:** 0.07 to 0.7 mg/kg/day divided every 12-24 hours. Usual maximum: 0.5 mg/kg/day or 20 mg/day. * **Lisinopril:** 0.07 to 0.2 mg/kg/day once daily. Usual maximum: 10 mg/day for children < 6 years, 20 mg/day for children 6-12 years. * **Ramipril:** 0.05 mg/kg/day once daily. Maximum: 5 mg/day. Dosing for pediatric patients requires careful titration and may be based on local protocols. ## Dose Adjustments * **Renal Impairment:** Dose reduction is typically required for patients with significant renal impairment (e.g., creatinine clearance < 30 mL/min). Specific reduction percentages vary by agent and severity of impairment. * **Hepatic Impairment:** Captopril and enalapril may require dose reduction in severe hepatic impairment due to altered metabolism. Other agents may also need caution. ## 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 (teratogenic risk, especially in the second and third trimesters). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Dry cough (most frequent), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in susceptible individuals), hyperkalemia, severe hypotension, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics/Potassium Supplements/Aliskiren/ARBs:** Increased risk of hyperkalemia. * **NSAIDs/COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of worsening renal function, especially in volume-depleted patients. * **Diuretics (Thiazide/Loop):** Increased risk of hypotension, especially upon initiation. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing the risk of lithium toxicity. * **Mammalian Target of Rapamycin (mTOR) Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Renal function (serum creatinine, BUN), electrolytes (potassium). * **During Treatment:** * Renal function and electrolytes within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Blood pressure. * Signs/symptoms of angioedema or hypersensitivity. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and is often dose-limiting. It may resolve after discontinuation but can persist for weeks or months. * Angioedema is a medical emergency; discontinue ACE inhibitor immediately and manage airway. * ACE inhibitors are generally renoprotective, particularly in diabetic patients with proteinuria, but can precipitate acute kidney injury in patients with bilateral renal artery stenosis or severe volume depletion. * Initial doses can cause significant hypotension, especially in patients taking diuretics or with volume depletion. Consider withholding diuretics temporarily or using a lower starting dose. * ACE inhibitors are generally safe and effective in pregnancy for women of reproductive potential who are not pregnant. *** **Disclaimer:** This information is for educational purposes only and does not substitute for professional medical advice. Always consult with a qualified healthcare provider to verify current prescribing information, dosing, and management strategies for any medication.