Ace%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# ACE Inhibitors ## Overview ACE inhibitors (e.g., benazepril, captopril, enalapril, lisinopril, ramipril) are a class of medications that block the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (HF) with reduced ejection fraction (HFrEF) * Post-myocardial infarction (MI) in patients with evidence of left ventricular dysfunction * Diabetic nephropathy (proteinuria reduction) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is generally recommended to achieve target blood pressure or clinical goals. * **Hypertension:** Initial doses are typically low, with gradual titration every 1-4 weeks. * Captopril: 6.25 mg to 12.5 mg orally once to three times daily. Maximum 450 mg/day. * Enalapril: 2.5 mg to 5 mg orally once or twice daily. Maximum 40 mg/day. * Lisinopril: 2.5 mg to 5 mg orally once daily. Maximum 40 mg/day. * Ramipril: 2.5 mg to 5 mg orally once daily. Maximum 20 mg/day. * Benazepril: 5 mg to 10 mg orally once daily. Maximum 80 mg/day. * **Heart Failure (HFrEF):** Doses often higher than for hypertension. Target doses vary by agent and are titrated based on patient tolerance and clinical response. * Enalapril: Target dose 10 mg to 20 mg orally twice daily. * Lisinopril: Target dose 10 mg to 20 mg orally once daily. * Ramipril: Target dose 5 mg orally twice daily (or 10 mg once daily). * **Post-MI:** Initiate within 24 hours in patients with anterior MI or evidence of LV dysfunction. * Captopril: Initiate 6.25 mg orally three times daily, then titrate up to 50 mg orally three times daily. * Enalapril: Initiate 2.5 mg orally twice daily, then titrate up to 10 mg orally twice daily. * **Diabetic Nephropathy:** * Lisinopril: 10 mg to 20 mg orally once daily. ## Pediatric Dosing Dosing in children is based on weight and is highly individualized. Clinical efficacy and safety data are more limited than in adults. * Enalapril: 0.07 mg/kg to 0.21 mg/kg orally once daily (max 40 mg/day). * Lisinopril: 0.07 mg/kg to 0.2 mg/kg orally once daily (max 20 mg/day). * Captopril: 0.3 mg/kg orally three times daily (max 150 mg/day). Dosing in neonates and infants requires careful consideration due to potential renal effects and is often guided by specialist recommendations. ## Dose Adjustments * **Renal Impairment:** Dose reduction and slower titration are necessary. Specific recommendations vary by agent and degree of renal impairment (eGFR). * Captopril: Reduce dose if eGFR < 30 mL/min/1.73m². * Enalapril: Reduce starting dose in moderate to severe renal impairment. * Lisinopril: Reduce starting dose in moderate to severe renal impairment. * **Hepatic Impairment:** Generally, no dose adjustment is needed for ACE inhibitors with good oral bioavailability (e.g., lisinopril, enalapril). Captopril and moexipril may require caution or dose adjustment due to first-pass metabolism. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment * Concomitant use of aliskiren in patients with diabetes mellitus or renal impairment * Pregnancy (second and third trimesters) ## Adverse Effects * **Most Common:** Dry cough, dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (potentially life-threatening, can occur at any time), acute kidney injury (especially in patients with bilateral renal artery stenosis or severe HF), hyperkalemia, hepatotoxicity (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, trimethoprim:** Increased risk of hyperkalemia. Monitor potassium closely. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in volume-depleted patients or those with pre-existing renal dysfunction. * **Diuretics:** Additive hypotensive effect. Initial dose reduction of ACE inhibitor may be necessary. * **Lithium:** ACE inhibitors can reduce lithium clearance, increasing lithium toxicity risk. Monitor lithium levels. * **ARBs, Aliskiren:** Increased risk of angioedema, hyperkalemia, and hypotension. Concomitant use is generally contraindicated or requires strict monitoring. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), BUN, eGFR. * **During Therapy:** * Blood pressure regularly. * Serum creatinine and electrolytes within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Monitor for signs/symptoms of angioedema, cough, dizziness, or hyperkalemia. ## Clinical Pearls * The dry cough is thought to be due to increased bradykinin levels and is reversible upon discontinuation. * Initiate at a low dose and titrate slowly, especially in patients who are elderly, volume-depleted, or have significant renal impairment. * First-dose hypotension can occur, particularly in patients taking diuretics. Consider holding diuretics prior to initiation or using a lower starting dose. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor and appropriate management. *** *Please verify current prescribing information and consult with a healthcare professional for specific patient care decisions.*