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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications 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 * Congestive Heart Failure (CHF) * Post-myocardial infarction (MI) (in select patients) * Diabetic nephropathy (in patients with type 1 diabetes and hypertension or proteinuria) ## Adult Dosing Dosages vary significantly by agent. Therapy is typically initiated at a low dose and titrated upwards based on patient response and tolerability. * **Hypertension:** Initial doses depend on the specific ACE inhibitor. For example: * Lisinopril: 10 mg PO once daily. Maximum 40 mg/day. * Enalapril: 5 mg PO once or twice daily. Maximum 40 mg/day. * Ramipril: 2.5 mg PO once daily. Maximum 20 mg/day. * **Heart Failure:** Initial doses are typically lower than for hypertension to avoid hypotension. * Lisinopril: 5 mg PO once daily. Target dose 20 mg/day. * Enalapril: 2.5 mg PO twice daily. Target dose 10 mg twice daily. * Ramipril: 1.25 mg PO once daily. Target dose 5 mg twice daily. * **Post-MI:** Initiate within 24 hours of symptom onset in patients with anterior MI, evidence of heart failure, or LV dysfunction. * Captopril: 6.25 mg PO TID, then titrate to 12.5 mg PO TID, then 25 mg PO TID. * Lisinopril: 5 mg PO once daily, then 10 mg PO once daily, then 20 mg PO once daily. ## Pediatric Dosing Dosing in pediatric patients is less established and varies by age and indication. Consult specific pediatric guidelines or product information. * **Hypertension:** * Captopril: 0.3 mg/kg/dose PO TID (max 6 mg/kg/day or 450 mg/day). * Enalapril: 0.07 mg/kg/dose PO once daily (max 0.61 mg/kg/day or 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Cautious titration is also advised in severe renal impairment. Dose reduction is often based on creatinine clearance. * **Hepatic Impairment:** Use with caution; generally no dose adjustment required, but monitor for potential accumulation. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (can be life-threatening), acute kidney injury, rash, neutropenia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride) & Potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics (especially thiazides):** Increased risk of symptomatic hypotension, especially with initiating ACE inhibitor therapy. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs (e.g., losartan):** Increased risk of renal impairment, hyperkalemia, and hypotension; generally not recommended for combination therapy. * **Sacubitril/Valsartan:** Do not initiate ACE inhibitors within 36 hours of the last dose of sacubitril/valsartan due to increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), CBC. * **During Therapy:** * Blood pressure: Monitor for hypotension. * Serum creatinine and potassium: Monitor periodically, especially in patients with renal impairment, heart failure, or those taking diuretics or potassium supplements. * Monitor for signs and symptoms of angioedema and infection. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels and usually resolves after discontinuation. * First-dose hypotension can occur, particularly in patients who are volume-depleted or on concurrent diuretic therapy. Consider withholding diuretics for 2-3 days prior to initiating ACE inhibitors if possible. * ACE inhibitors are generally renoprotective in diabetic patients with proteinuria. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. * ACE inhibitors should be avoided in pregnancy due to teratogenicity. *** *Please verify current prescribing information for the most up-to-date details on dosing, contraindications, and interactions.*