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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of drugs 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 * Congestive Heart Failure (CHF) * Left Ventricular Dysfunction post-Myocardial Infarction (MI) * Diabetic Nephropathy ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Doses are typically started low and titrated upwards. * **Hypertension:** * Benazepril: 10-40 mg once daily. Max: 80 mg/day. * Captopril: 25 mg 2-3 times daily. Max: 150 mg 3 times daily. * Enalapril: 5-20 mg once or twice daily. Max: 40 mg/day. * Fosinopril: 10-40 mg once daily. Max: 80 mg/day. * Lisinopril: 10 mg once daily. Max: 40 mg/day. * Moexipril: 7.5-15 mg once daily. Max: 30 mg/day. * Perindopril: 5-10 mg once daily. Max: 20 mg/day. * Quinapril: 10-40 mg once or twice daily. Max: 80 mg/day. * Ramipril: 2.5-5 mg once daily. Max: 10 mg/day. * Trandolapril: 1-4 mg once daily. Max: 8 mg/day. * **Heart Failure:** * Dosing is typically initiated at the lower end of the range and titrated based on tolerance and clinical response. Specific maximum doses may be lower than for hypertension to improve tolerability. * **Post-MI:** * Dosing often starts within 24 hours of symptom onset. Specific starting doses and titration schedules vary by agent. ## Pediatric Dosing Dosing in children is less established and generally based on weight. Consult specific pediatric guidelines or drug monographs. * **Hypertension (general guidelines, consult specific agent):** * Enalapril: 0.07 mg/kg/day to 0.75 mg/kg/day divided once or twice daily. Max: 40 mg/day. * Lisinopril: 0.07 mg/kg/day to 0.75 mg/kg/day divided once daily. Max: 40 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly for renally excreted ACE inhibitors (e.g., Captopril, Enalapril, Lisinopril). Monitor serum creatinine and potassium. * **Hepatic Impairment:** Generally, no dose adjustment is needed unless there is severe hepatic insufficiency. * **Volume Depletion:** Initiate at a lower dose and titrate cautiously. * **Concomitant Diuretic Therapy:** Discontinue diuretics 2-3 days prior to initiating ACE inhibitors, or start ACE inhibitors at a lower dose. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters; Category C in 1st trimester). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Less Common/Serious:** Angioedema (potentially life-threatening), renal impairment (especially in patients with bilateral renal artery stenosis), rash, altered taste, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Salt Substitutes:** Increased risk of hyperkalemia. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid in patients with diabetes or renal impairment. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in volume-depleted patients or those with pre-existing renal disease. * **Lithium:** ACE inhibitors can reduce renal clearance of lithium, leading to lithium toxicity. Monitor lithium levels closely. * **mTOR Inhibitors (e.g., sirolimus, everolimus), DPP-4 Inhibitors (e.g., sitagliptin):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor for symptomatic hypotension. * **Renal Function:** Monitor serum creatinine and BUN, especially at baseline, with dose increases, and in patients with risk factors. * **Serum Potassium:** Monitor regularly, especially in patients with renal impairment, diabetes, or concomitant use of potassium-sparing agents. * **Signs of Angioedema:** Educate patients to report any swelling, especially of the face, lips, tongue, or throat, immediately. ## Clinical Pearls * The characteristic dry cough is often dose-limiting and may resolve upon discontinuation. * Angioedema is a rare but serious adverse effect that can occur at any time and requires immediate discontinuation of the ACE inhibitor and prompt medical attention. * Initiate therapy at low doses, particularly in elderly patients, those with heart failure, or those on diuretic therapy, to minimize the risk of hypotension. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. *** ***Disclaimer:** This information is intended for clinical use and does not replace comprehensive drug information resources. Always consult the most current prescribing information for specific agents and individual patient needs. Dosing and recommendations may vary based on local protocols and clinical judgment.