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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and stimulates aldosterone secretion, leading to sodium and water retention. By inhibiting angiotensin II formation, ACE inhibitors cause vasodilation and reduce sodium and water retention, thus lowering blood pressure. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing varies significantly by agent. Doses should be titrated to achieve target blood pressure or clinical response. * **Hypertension:** Common starting doses vary widely. For example: * Lisinopril: 10 mg PO once daily. Maximum: 40 mg/day. * Enalapril: 5 mg PO once or twice daily. Maximum: 20 mg/day (once daily) or 40 mg/day (twice daily). * Ramipril: 2.5 mg PO once daily. Maximum: 10 mg/day. * **Heart Failure:** Common starting doses vary widely. For example: * Enalapril: 2.5 mg PO twice daily. Target dose typically 10 mg PO twice daily. * Lisinopril: 5 mg PO once daily. Target dose typically 20 mg PO once daily. * Ramipril: 1.25 mg PO once daily. Target dose typically 5 mg PO once daily. * **Post-MI:** Common starting doses vary widely. For example: * Ramipril: 1.25 mg PO once daily. Titrate as tolerated. * **Diabetic/Proteinuric Kidney Disease:** Similar to hypertension dosing, titrated to achieve target blood pressure and reduce proteinuria. *Specific starting doses and titration schedules are often guided by local protocol and patient-specific factors.* ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and heart failure. Dosing is weight-based and varies by agent. * **Enalapril:** Hypertension: 0.08-0.1 mg/kg/dose PO once or twice daily. Maximum: 0.6 mg/kg/day (or 40 mg/day). Heart failure: 0.1 mg/kg/dose PO once or twice daily. * **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/day PO once daily. Maximum: 20 mg/day. * **Captopril:** Hypertension: 0.3-0.5 mg/kg/dose PO three times daily. * **Ramipril:** Hypertension: 0.05 mg/kg/dose PO once daily. *Pediatric dosing requires careful monitoring and adherence to age- and weight-appropriate guidelines.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary in patients with impaired renal function, particularly those with significant proteinuria. The degree of reduction depends on the specific ACE inhibitor and the level of renal dysfunction. * **Hepatic Impairment:** Generally, dose adjustments are not required for mild to moderate hepatic impairment. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). * Hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, hyperkalemia, headache, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, neutropenia/agranulocytosis (rare), hepatotoxicity. ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Aldosterone Antagonists, ARBs:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 Inhibitors:** May blunt antihypertensive effect and increase risk of renal impairment. * **Diuretics (Thiazide, Loop):** Increased risk of hypotension, especially with the first dose of ACE inhibitor. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concurrent use, especially in patients with diabetes. * **Lithium:** Increased lithium levels and risk of toxicity. * **Mammalian Target of Rapamycin (mTOR) Inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. Do not administer ACE inhibitors within 36 hours of switching to or initiating sacubitril/valsartan. ## Monitoring * **Renal Function:** Baseline and periodically (serum creatinine, BUN). * **Electrolytes:** Baseline and periodically (serum potassium). * **Blood Pressure:** Regularly to assess efficacy and titrate dose. * **Signs of Angioedema:** Patient education is crucial. * **Complete Blood Count (CBC):** Consider in patients at risk for neutropenia. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels and typically resolves upon discontinuation of the medication. * First-dose hypotension is a risk, especially in patients who are volume-depleted or on diuretics. Administer the first dose with caution and monitor closely. * Angioedema can occur at any time during treatment and can be life-threatening. Patients should seek immediate medical attention if swelling of the face, lips, tongue, or throat occurs. * ACE inhibitors are generally considered safe and effective in pregnancy for the first trimester, but are contraindicated in the second and third trimesters due to the risk of fetal harm. * ACE inhibitors should be initiated at low doses and titrated slowly, especially in patients with heart failure or renal impairment. *** *This information is intended for healthcare professionals and does not replace a thorough review of current prescribing information for specific ACE inhibitor products. Always consult the latest drug monographs, institutional protocols, and patient-specific factors before initiating or adjusting therapy.*