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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications that primarily work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI management for specific patients) * Diabetic nephropathy (in patients with type 1 diabetes and proteinuria) * Chronic kidney disease (in select patients to slow progression) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is generally performed slowly. * **Benazepril:** Hypertension: 10-40 mg once daily. Heart Failure: 5 mg once daily, titrate up to 40 mg once daily. * **Captopril:** Hypertension: 25-150 mg twice daily (divided doses). Heart Failure: 6.25-12.5 mg three times daily, titrate up to 50 mg three times daily. * **Enalapril:** Hypertension: 10-40 mg once daily. Heart Failure: 2.5-5 mg once daily, titrate up to 20 mg once daily (divided into 1-2 doses). * **Fosinopril:** Hypertension: 10-40 mg once daily. Heart Failure: 5-10 mg once daily, titrate up to 40 mg once daily. * **Lisinopril:** Hypertension: 10-40 mg once daily. Heart Failure: 5 mg once daily, titrate up to 40 mg once daily. * **Moexipril:** Hypertension: 7.5-30 mg once daily. * **Perindopril:** Hypertension: 5-10 mg once daily. Heart Failure: 2.5-5 mg once daily, titrate up to 10 mg once daily. * **Quinapril:** Hypertension: 10-80 mg once daily (divided into 1-2 doses). Heart Failure: 5 mg twice daily, titrate up to 20 mg twice daily. * **Ramipril:** Hypertension: 2.5-20 mg once daily. Heart Failure: 1.25-2.5 mg once daily, titrate up to 10 mg once daily. * **Trandolapril:** Hypertension: 1-4 mg once daily. Heart Failure: 1 mg once daily, titrate up to 4 mg once daily. **Maximum doses vary by indication and specific drug.** ## Pediatric Dosing ACE inhibitor use in pediatrics is typically limited to patients with hypertension or heart failure. Dosing is based on weight and often requires careful titration due to immature renal and hepatic function. Specific dosing protocols may vary by institution. * **Enalapril:** Hypertension: 0.07-0.1 mg/kg/day, max 40 mg/day. * **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/day, max 40 mg/day. * **Ramipril:** Hypertension: 0.05 mg/kg/day, max 10 mg/day. **Specific pediatric dosing is often guided by specialist recommendations or institutional protocols.** ## Dose Adjustments * **Renal Impairment:** Initiate at lower doses and titrate cautiously. Captopril and fosinopril may require less adjustment than others due to different elimination pathways. * **Hepatic Impairment:** Use with caution, especially with highly protein-bound agents like enalapril and quinapril. Start with lower doses. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment * Concomitant use with aliskiren in patients with diabetes or renal impairment * Pregnancy (especially second and third trimesters) * Hypersensitivity to the drug or other ACE inhibitors ## Adverse Effects * **Hypotension:** Especially in volume-depleted patients or those on diuretics. * **Hyperkalemia:** Monitor potassium levels, particularly in patients with renal impairment or on potassium-sparing diuretics. * **Cough:** Dry, persistent cough is a common side effect, often leading to discontinuation. * **Angioedema:** Rare but serious, can affect the face, lips, tongue, throat, and intestines. Seek immediate medical attention. * **Renal dysfunction:** Can occur, especially in patients with pre-existing renal disease or bilateral renal artery stenosis. * **Dizziness, fatigue, headache.** * **Rash.** ## Key Drug Interactions * **Potassium supplements and potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of symptomatic hypotension. Consider stopping or reducing diuretic dose before starting ACE inhibitor. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in the elderly or volume-depleted. * **Lithium:** ACE inhibitors can reduce renal clearance of lithium, increasing lithium levels and toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Concomitant use is contraindicated due to increased risk of angioedema. Separate administration by at least 36 hours. ## Monitoring * **Blood pressure:** Regularly, especially during initiation and dose titration. * **Renal function (serum creatinine, BUN):** Before treatment, at 1-2 weeks, and periodically thereafter. * **Serum potassium:** Before treatment, at 1-2 weeks, and periodically thereafter. * **Signs and symptoms of angioedema and hypersensitivity reactions.** * **Signs and symptoms of heart failure:** For patients with this indication. ## Clinical Pearls * ACE inhibitors are often first-line therapy for hypertension, heart failure, and post-MI management. * Initiate at low doses and titrate slowly to minimize adverse effects, especially hypotension and cough. * The dry cough is dose-related and may resolve with dose reduction or switching to an angiotensin II receptor blocker (ARB). * Discontinue immediately if angioedema is suspected. * Monitor for hyperkalemia, particularly in patients with renal impairment or those taking potassium-sparing agents. * Patient education regarding potential side effects and when to seek medical attention is crucial. *** *This information is intended for educational purposes and does not substitute for professional medical advice. Always verify current prescribing information and consult with a healthcare provider for specific patient care decisions.*