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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications used primarily 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 * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI, reduce mortality and reinfarction) * Diabetic nephropathy (reduce proteinuria) ## Adult Dosing Dosing varies significantly by agent. Doses should be initiated low and titrated upwards based on clinical response and tolerability. * **Benazepril:** Start 10 mg once daily, titrate to 20-40 mg once daily. * **Captopril:** Start 25 mg twice daily, titrate to 75-150 mg twice daily. * **Enalapril:** Start 2.5-5 mg once or twice daily, titrate to 10-40 mg once or twice daily. * **Fosinopril:** Start 10 mg once daily, titrate to 20-40 mg once daily. * **Lisinopril:** Start 5-10 mg once daily, titrate to 20-40 mg once daily. Maximum 40 mg daily in hypertension; higher doses may be used in heart failure under specialist guidance. * **Moexipril:** Start 7.5 mg once daily, titrate to 15-30 mg once daily. * **Perindopril:** Start 2.5-5 mg once daily, titrate to 10 mg once daily. * **Quinapril:** Start 5-10 mg twice daily, titrate to 20-80 mg twice daily. * **Ramipril:** Start 2.5 mg once daily, titrate to 10 mg once daily. * **Trandolapril:** Start 1 mg once daily, titrate to 4 mg once daily. ## Pediatric Dosing ACE inhibitor dosing in pediatrics is less well-established and often based on weight. Doses should be individualized and started at the lower end of the range. * **Enalapril:** 0.1 mg/kg/day to a maximum of 0.5 mg/kg/day, divided once or twice daily. * **Lisinopril:** 0.07 mg/kg/day to a maximum of 0.61 mg/kg/day (or 20 mg), once daily. * **Ramipril:** 0.05 mg/kg/day to a maximum of 0.1 mg/kg/day, divided once or twice daily. ## Dose Adjustments * **Renal Impairment:** Dose reduction is generally required, particularly for renally excreted ACE inhibitors (e.g., enalapril, lisinopril, ramipril). Consult specific agent guidelines. Captopril and fosinopril are less reliant on renal excretion. * **Hepatic Impairment:** Generally no dose adjustment needed, but caution is advised. ## 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 (especially in the second and third trimesters). ## Adverse Effects * **Dry cough:** Most common, thought to be due to bradykinin accumulation. * **Angioedema:** Rare but potentially life-threatening; can occur at any time. * **Hyperkalemia:** Especially in patients with renal impairment or on potassium-sparing diuretics/potassium supplements. * **Hypotension:** Particularly with initial doses or in volume-depleted patients. * **Renal impairment:** Can worsen pre-existing renal dysfunction, especially in patients with bilateral renal artery stenosis. * **Dizziness, fatigue.** * **Rash, dysgeusia.** ## Key Drug Interactions * **Potassium supplements and potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **Lithium:** ACE inhibitors can increase lithium levels. * **Aliskiren:** Increased risk of hyperkalemia and hypotension, particularly in patients with diabetes or renal impairment. * **ARBs (Angiotensin II Receptor Blockers):** Avoid concomitant use due to increased risk of adverse events without added benefit. ## Monitoring * **Blood pressure:** Regularly, especially after dose initiation or titration. * **Renal function (serum creatinine, BUN):** Baseline and periodically, especially in patients with renal impairment or risk factors. * **Serum potassium:** Baseline and periodically, especially in patients with renal impairment or on other medications that affect potassium. * **Signs and symptoms of angioedema or hypersensitivity.** ## Clinical Pearls * ACE inhibitors are renoprotective in diabetic patients with proteinuria. * Cough is usually dose-dependent and may resolve upon discontinuation or switching to a different class of antihypertensive. * Monitor for first-dose hypotension, especially in patients taking diuretics or those with heart failure. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. * In cases of severe angioedema, consider treatment with epinephrine and antihistamines. *** **Disclaimer:** This information is intended for clinical decision support and does not replace the need to consult the most current prescribing information and local institutional protocols. Dosing and safety parameters can vary. Always verify with the official product monograph or reliable drug information resources.