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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used to manage cardiovascular diseases. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Acute myocardial infarction (post-MI management) * Diabetic nephropathy * Chronic kidney disease (CKD) with proteinuria ## Adult Dosing Dosing varies significantly between agents. Typical starting and maximum doses (mg/day) include: * **Benazepril:** Start 5-10 mg once daily; Max 40 mg once daily. * **Captopril:** Start 25 mg twice daily; Max 150 mg twice daily (tid also used). * **Enalapril:** Start 2.5-5 mg once daily; Max 20 mg once daily (40 mg/day for severe heart failure). * **Fosinopril:** Start 10 mg once daily; Max 40 mg once daily. * **Lisinopril:** Start 5-10 mg once daily; Max 40 mg once daily. * **Moexipril:** Start 7.5 mg once daily; Max 30 mg once daily. * **Perindopril:** Start 2.5-5 mg once daily; Max 10 mg once daily. * **Quinapril:** Start 5-10 mg twice daily; Max 40 mg twice daily. * **Ramipril:** Start 2.5 mg once daily; Max 10 mg once daily. * **Trandolapril:** Start 0.5-1 mg once daily; Max 4 mg once daily. *Note: Dosing for heart failure often starts lower and titrates up more slowly.* ## Pediatric Dosing ACE inhibitors are generally not first-line agents in pediatric hypertension unless specific comorbidities exist. Dosing is typically based on weight and ranges: * **Enalapril:** 0.07-0.1 mg/kg/day orally, divided twice daily. Max 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** 0.07-0.2 mg/kg/day orally, once daily. Max 20 mg/day for younger children (<6 years) and 40 mg/day for older children. *Note: Dosing in pediatric populations can be complex and requires careful monitoring. Refer to specific pediatric guidelines.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially with creatinine clearance <30 mL/min. Captopril and enalapril are often preferred in severe renal impairment due to less accumulation. * **Hepatic Impairment:** Use with caution; starting doses may need to be lower. ## 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 (second and third trimesters). ## Adverse Effects * **Dry cough:** Most common, dose-dependent, typically reversible upon discontinuation. * **Hyperkalemia:** Risk increases with renal impairment or concomitant potassium-sparing diuretics/potassium supplements. * **Hypotension:** Especially with the first dose or in volume-depleted patients. * **Angioedema:** Rare but potentially life-threatening; involves swelling of the face, lips, tongue, throat, or intestines. * **Renal impairment:** Can occur, particularly in patients with bilateral renal artery stenosis. * **Other:** Dizziness, fatigue, rash, dysgeusia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride) and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction. * **Diuretics (especially loop and thiazide):** Increased risk of symptomatic hypotension. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in patients with diabetes. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **Lithium:** ACE inhibitors can increase lithium levels, leading to toxicity. ## Monitoring * **Blood Pressure:** Regularly, especially after initiation and dose changes. * **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment or on other agents affecting potassium. * **Renal Function (Serum Creatinine/BUN):** Baseline and periodically. * **Angioedema:** Patients should be educated to report any swelling immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor and prompt management. * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Due to the risk of fetal harm, ACE inhibitors must be discontinued as soon as pregnancy is detected. * Initiate at low doses and titrate slowly, particularly in elderly, volume-depleted, or renally impaired patients, to minimize the risk of hypotension. * ARBs are an alternative class for patients who develop cough or angioedema with ACE inhibitors (though cross-reactivity for angioedema exists). *** *Disclaimer: This information is for clinical decision support and does not replace professional judgment. Always consult the most current prescribing information for the specific drug product being used.*