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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to manage hypertension and heart failure by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation and reduced sodium and water retention. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI in patients with signs of heart failure or LV dysfunction) * Diabetic nephropathy (in patients with hypertension or type 1 diabetes) ## Adult Dosing Dosing varies by specific ACE inhibitor and indication. Titration is often required. * **Hypertension:** * Benazepril: Start 10 mg once daily, titrate to 20-40 mg once daily. Max 80 mg/day. * Captopril: Start 25 mg twice daily, titrate to 50 mg three times daily. Max 150 mg three times daily. * Enalapril: Start 5 mg once daily, titrate to 10-20 mg once or twice daily. Max 40 mg/day. * Enalaprilat (IV): Start 0.625 mg every 6 hours, titrate to 1.25 mg every 6 hours. Max 5 mg every 6 hours. * Fosinopril: Start 10 mg once daily, titrate to 20-40 mg once daily. Max 80 mg/day. * Lisinopril: Start 10 mg once daily, titrate to 20-40 mg once daily. Max 80 mg/day. * Moexipril: Start 7.5 mg once daily, titrate to 15 mg once daily. Max 30 mg/day. * Perindopril: Start 5 mg once daily, titrate to 10 mg once daily. Max 20 mg/day. * Quinapril: Start 10 mg once or twice daily, titrate to 20-40 mg twice daily. Max 80 mg/day. * Ramipril: Start 2.5 mg once daily, titrate to 5-10 mg once daily. Max 20 mg/day. * Trandolapril: Start 1 mg once daily, titrate to 2-4 mg once daily. Max 8 mg/day. * **Heart Failure:** Dosing typically starts lower and is titrated more slowly. Consult specific guidelines (e.g., ACC/AHA) for target doses. * **Post-MI:** Often initiated within 24 hours. Example: Lisinopril 5 mg daily, may increase to 10 mg daily after 24 hours, then to 20 mg daily after 24 hours. ## Pediatric Dosing ACE inhibitors are generally not first-line agents in pediatric hypertension. Dosing is highly individualized and based on age, weight, and clinical response. Consult pediatric hypertension guidelines or specialist literature for specific recommendations. Limited data exists for many ACE inhibitors in pediatric populations. * Enalapril: Generally initiated at 0.07 mg/kg/day divided into 2 doses. Max 0.5 mg/kg/day or 40 mg/day. * Lisinopril: Generally initiated at 0.07 mg/kg/day once daily. Max 0.61 mg/kg/day or 40 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce starting dose and titrate cautiously. Specific adjustments depend on the agent and GFR. Generally, monitor potassium and renal function closely. * For many agents, initial doses may be halved in moderate renal impairment (e.g., CrCl < 30-40 mL/min). * **Hepatic Impairment:** Use with caution, especially agents with hepatic metabolism. Dosing adjustments may be necessary. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (teratogenic effects). * Known hypersensitivity to the specific ACE inhibitor. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Less Common:** Angioedema (rare but life-threatening), rash, dysgeusia, renal insufficiency/failure (especially in patients with bilateral renal artery stenosis), neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride), Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May attenuate antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (especially thiazides or loop diuretics):** Increased risk of symptomatic hypotension, particularly after initiating ACE inhibitor therapy. * **Lithium:** ACE inhibitors can reduce renal clearance of lithium, increasing the risk of lithium toxicity. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. Do not use concomitantly; allow a 36-hour washout period after stopping an ACE inhibitor before initiating sacubitril/valsartan, and vice-versa. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction; contraindicated in patients with diabetes. ## Monitoring * **Before initiation:** Baseline serum creatinine, potassium, and blood pressure. * **During therapy:** * Renal function (serum creatinine) and electrolytes (potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Blood pressure regularly. * Monitor for signs/symptoms of angioedema, cough, and hyperkalemia. * Consider CBC with differential in patients with renal impairment or collagen vascular disease. ## Clinical Pearls * Cough is a dose-limiting side effect for many patients; consider switching to an angiotensin II receptor blocker (ARB) if cough is bothersome. * First-dose hypotension can occur, especially in volume-depleted patients or those on diuretics. Consider a lower starting dose or temporarily withholding diuretics. * ACE inhibitors are generally renoprotective in diabetic nephropathy and should be used in patients with proteinuria unless contraindicated. * Angioedema is a medical emergency; discontinue the ACE inhibitor immediately and manage the airway. * Dosing for heart failure and post-MI often requires slow titration to target doses based on patient tolerance and clinical response; consult specific guidelines. *** *Disclaimer: This information is intended for clinical decision-making and does not replace full prescribing information. Always consult the current official drug labeling or a reliable drug information resource for complete and up-to-date prescribing information, including contraindications, warnings, precautions, and adverse reactions.*