Ace%252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications that block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and stimulates aldosterone release, leading to sodium and water retention. By inhibiting its formation, ACE inhibitors cause vasodilation and reduce sodium and water retention, thereby lowering blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI with reduced ejection fraction) * Diabetic nephropathy (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient factors. Titration is typically required. * **Hypertension:** * Benazepril: 10-40 mg once daily * Captopril: 25-150 mg divided every 8-12 hours (max 450 mg/day) * Enalapril: 5-40 mg once or twice daily * Fosinopril: 10-40 mg once daily * Lisinopril: 10-40 mg once daily (max 80 mg/day) * Moexipril: 7.5-30 mg once daily * Perindopril: 5-20 mg once daily * Quinapril: 10-80 mg divided every 12 hours * Ramipril: 2.5-20 mg once daily * Trandolapril: 1-8 mg once daily * *Note:* Initial doses may be lower in patients at risk for hypotension (e.g., volume depleted, hyponatremic). * **Heart Failure:** * Enalapril: 2.5-20 mg twice daily (max 40 mg/day) * Captopril: 6.25-50 mg three times daily (max 150 mg/day) * Lisinopril: 5-20 mg once daily (max 40 mg/day) * Ramipril: 2.5-10 mg once daily * *Note:* Initiation at lower doses and gradual titration is crucial. * **Post-MI:** * Captopril: 6.25 mg once, increasing to 12.5 mg twice daily, then 25 mg twice daily, then 50 mg twice daily as tolerated (typically started within 24 hours of MI). * Enalapril: 5 mg once daily, increasing to 10 mg twice daily, then 20 mg once daily as tolerated. * Lisinopril: 5 mg once daily, increasing to 10 mg once daily, then 20 mg once daily as tolerated. * Ramipril: 2.5 mg three times daily, increasing to 5 mg twice daily, then 10 mg twice daily as tolerated. * **Diabetic Nephropathy:** * Lisinopril: 10-20 mg once daily. * Ramipril: 5-10 mg once daily. * *Note:* Target is often the lowest blood pressure that is safe and effective, with a goal of reducing proteinuria. ## Pediatric Dosing Dosing in pediatrics is often based on weight and requires careful titration. Consult specific pediatric guidelines or institutional protocols. * **Hypertension:** Doses vary significantly by age and weight. For example: * Enalapril: 0.07-0.1 mg/kg/dose every 12-24 hours (max 0.6 mg/kg/day or 40 mg/day). * Lisinopril: 0.07-0.2 mg/kg/dose once daily (max 20 mg/day). * *Note:* Always verify current pediatric dosing recommendations. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate more slowly. Dose adjustments are specific to the individual ACE inhibitor and the degree of renal impairment (based on creatinine clearance). * Lisinopril: CrCl < 30 mL/min, start at 5 mg/day; 30-60 mL/min, start at 10 mg/day. * Captopril: Higher doses may require more frequent monitoring or adjustment. * **Hepatic Impairment:** Usually minimal dose adjustment is needed for agents not extensively metabolized by the liver. For agents like enalapril, which undergo hepatic activation to enalaprilat, caution and slower titration 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 or moderate to severe renal impairment. * Pregnancy (Category D in 2nd and 3rd trimesters). ## Adverse Effects * **Common:** Dry cough (most common), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Less Common/Serious:** Angioedema (can be life-threatening), acute kidney injury (especially in patients with bilateral renal artery stenosis), rash, taste disturbances, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride), potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs (including aspirin):** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients or those with pre-existing renal disease. * **Diuretics (especially loop and thiazide):** Increased risk of hypotension, particularly after the first dose of the ACE inhibitor. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels closely. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., sitagliptin):** Increased risk of angioedema. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment; contraindicated in patients with diabetes or moderate to severe renal impairment. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium), urinalysis. * **During Titration:** Blood pressure, serum creatinine, potassium. * **Long-term:** Blood pressure, periodic monitoring of renal function and electrolytes. * **For cough:** Monitor for resolution upon discontinuation. * **For angioedema:** Immediate discontinuation and close monitoring. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an angiotensin II receptor blocker (ARB). * First-dose hypotension can occur, especially in patients who are volume-depleted or taking diuretics. Administer the initial dose at bedtime or monitor closely. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Angioedema is a rare but serious side effect that can occur at any time during treatment and requires immediate discontinuation. * Monitor potassium closely, especially in patients with renal impairment, those taking potassium supplements, or potassium-sparing diuretics. * Do not use in pregnancy; switch to an alternative medication if pregnancy is planned or confirmed. *** **Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete details and to confirm drug appropriateness for a specific patient.