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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 decreased aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI, left ventricular dysfunction) * Diabetic nephropathy * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosing varies by specific agent. Doses are typically initiated low and titrated upwards based on patient response and tolerability. * **Benazepril:** Start 5-10 mg PO once daily; max 40 mg/day. * **Captopril:** Start 12.5-25 mg PO BID-TID; max 450 mg/day. (Note: Shorter half-life, requires more frequent dosing). * **Enalapril:** Start 2.5-5 mg PO once or BID; max 40 mg/day. * **Fosinopril:** Start 10 mg PO once daily; max 80 mg/day. * **Lisinopril:** Start 5-10 mg PO once daily; max 40 mg/day. * **Moexipril:** Start 7.5 mg PO once daily; max 30 mg/day. * **Perindopril:** Start 2.5-5 mg PO once daily; max 10 mg/day. * **Quinapril:** Start 5-10 mg PO BID; max 80 mg/day. * **Ramipril:** Start 1.25-2.5 mg PO once daily; max 10 mg/day. * **Trandolapril:** Start 0.5-1 mg PO once daily; max 4 mg/day. ## Pediatric Dosing ACE inhibitors are used in pediatrics for hypertension and heart failure. Dosing varies significantly by age and indication. Specific protocols should be consulted. * **Enalapril:** Hypertension: 0.07-0.2 mg/kg/dose PO q24h (max 5 mg/day in <6 years, max 20 mg/day in ≥6 years). * **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/dose PO q24h (max 5 mg/day in <6 years, max 20 mg/day in ≥6 years). * **Ramipril:** Hypertension: 0.05 mg/kg/dose PO q24h (max 2.5 mg/day). ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in patients with significant renal dysfunction (CrCl < 30 mL/min). Specific reduction guidance depends on the agent. * **Hepatic Impairment:** Captopril and enalapril are renally excreted; others may require dose adjustment due to hepatic metabolism. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus. * Concomitant use with sacubitril/valsartan (for at least 36 hours after the last dose of sacubitril/valsartan). * Pregnancy (especially second and third trimesters). * Hypersensitivity to the drug. ## Adverse Effects * Cough (dry, persistent) - most common * Angioedema (rare but serious, can be life-threatening) * Hyperkalemia * Hypotension (especially with first dose or in volume-depleted patients) * Renal dysfunction (especially in patients with bilateral renal artery stenosis) * Dizziness, fatigue * Rash * Dysgeusia (altered taste) ## Key Drug Interactions * **Potassium-sparing diuretics, Potassium supplements, Spironolactone, Eplerenone, Salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May decrease antihypertensive effect and increase risk of renal dysfunction, especially in elderly or volume-depleted patients. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in diabetics. * **Sacubitril/Valsartan:** Increased risk of angioedema and hyperkalemia. ACE inhibitors should not be initiated within 36 hours of completing sacubitril/valsartan. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium levels and toxicity risk. * **Diuretics:** Additive hypotensive effect. Increased risk of renal dysfunction if diuresis is excessive. ## Monitoring * **Blood Pressure:** Regularly monitor for hypotension and efficacy. * **Renal Function:** Monitor serum creatinine and BUN, particularly at initiation, dose increases, and in patients with renal impairment or risk factors. * **Serum Potassium:** Monitor regularly, especially in patients with renal impairment, hyperkalemia risk factors, or concomitant use of potassium-sparing agents. * **Angioedema:** Educate patients to report any swelling of the face, lips, tongue, or throat immediately. ## Clinical Pearls * The characteristic dry cough is often dose-limiting and can occur months after initiation. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB). * First-dose hypotension is more likely in patients who are volume-depleted or taking diuretics. Consider a lower starting dose and withhold diuretics temporarily if possible. * ACE inhibitors are generally contraindicated in pregnancy due to the risk of fetal harm. * Monitor for hyperkalemia, particularly in patients with underlying renal disease or those taking other drugs that affect potassium levels. * Discontinue ACE inhibitors immediately if angioedema occurs. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information or product monograph for complete details before making clinical decisions.*