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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used to treat 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 (systolic dysfunction) * Post-myocardial infarction (MI) for individuals with impaired left ventricular function or clinical signs of heart failure. * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient tolerance. Titration is crucial. * **Hypertension:** * **Benazepril:** Start 10 mg PO daily, titrate up to 40 mg PO daily. * **Captopril:** Start 25 mg PO BID, titrate up to 50 mg PO TID. * **Enalapril:** Start 5 mg PO daily, titrate up to 40 mg PO daily (single or divided doses). * **Fosinopril:** Start 10 mg PO daily, titrate up to 40 mg PO daily. * **Lisinopril:** Start 10 mg PO daily, titrate up to 40 mg PO daily. * **Moexipril:** Start 7.5 mg PO daily, titrate up to 30 mg PO daily. * **Perindopril:** Start 4 mg PO daily, titrate up to 16 mg PO daily. * **Quinapril:** Start 10 mg PO BID, titrate up to 40 mg PO BID. * **Ramipril:** Start 2.5 mg PO daily, titrate up to 10 mg PO daily. * **Trandolapril:** Start 1 mg PO daily, titrate up to 8 mg PO daily. * **Heart Failure:** Doses are typically higher than for hypertension, requiring careful titration. Consult specific drug monographs for detailed titration schedules and maximum doses. * **Post-MI:** Initiation usually occurs within 24-48 hours. Dosing depends on the specific agent and patient status. * **Diabetic Nephropathy:** Doses vary by agent and degree of proteinuria. ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and heart failure. Dosing is weight-based and requires careful monitoring. * **Enalapril:** 0.07 to 0.1 mg/kg/dose PO every 12 to 24 hours. Maximum dose 0.5 mg/kg/day. * **Lisinopril:** 0.07 mg/kg/dose PO once daily. Maximum dose 20 mg/day. * Other agents may have established pediatric dosing; consult specific drug information. ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally recommended for patients with creatinine clearance < 30 mL/min. Specific recommendations vary by agent. * **Hepatic Impairment:** Cautious use and potential dose reduction, particularly for prodrugs like enalapril and ramipril. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Second and third trimesters of pregnancy. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hypotension, hyperkalemia. * **Serious:** Angioedema (including laryngeal edema), renal failure (especially in patients with bilateral renal artery stenosis), neutropenia/agranulocytosis (rare), hepatotoxicity (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in volume-depleted patients or those with underlying renal disease. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use, especially in patients with diabetes or renal impairment. * **ARBs:** Increased risk of hyperkalemia, hypotension, and renal impairment. Generally avoided. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. * **Diuretics:** Increased risk of symptomatic hypotension, especially with concurrent diuretic use. ## Monitoring * **Blood Pressure:** Regularly monitor for therapeutic effect and hypotension. * **Renal Function:** Serum creatinine and BUN, especially at initiation and with dose changes, or in patients with renal risk factors. * **Potassium:** Serum potassium levels, particularly in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics. * **Angioedema:** Educate patients on signs and symptoms and to discontinue immediately if they occur. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * Initiate at a low dose and titrate slowly, especially in elderly patients, volume-depleted patients, or those with renal impairment. * First-dose hypotension can occur, particularly in patients taking diuretics. Consider withholding diuretics for 2-3 days prior to initiating ACE inhibitor therapy or starting with a lower dose. * ACE inhibitors are generally safe and effective in diabetic patients and can provide renoprotective benefits. * Discontinue ACE inhibitors if angioedema occurs and never restart. *** *Disclaimer: This information is intended for healthcare professionals. Always refer to the most current prescribing information and consult with a healthcare provider for specific patient care decisions.*