Ace%2525252525252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity. ## Primary Indications * Hypertension * Heart failure (NYHA class II-IV) * Left ventricular dysfunction post-myocardial infarction * Diabetic nephropathy (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor and indication. Titration is typically guided by patient response and tolerability. * **Hypertension:** Initial doses vary widely. Common starting doses include: * Lisinopril: 10 mg orally once daily. * Enalapril: 5 mg orally once or twice daily. * Ramipril: 2.5 mg orally once daily. * Maximum doses also vary, e.g., Lisinopril up to 40 mg daily, Enalapril up to 40 mg daily, Ramipril up to 10 mg daily. * **Heart Failure:** Initial doses are typically lower than for hypertension. Titration is usually slower. * Lisinopril: 5 mg orally once daily, titrate up to 20-40 mg once daily. * Enalapril: 2.5 mg orally twice daily, titrate up to 10 mg twice daily. * Ramipril: 1.25 mg orally once daily, titrate up to 5 mg twice daily. * **Post-MI:** Enalapril 5 mg orally twice daily or Lisinopril 5 mg orally once daily, increasing to 10 mg twice daily and 10 mg daily respectively, as tolerated. * **Diabetic Nephropathy:** Ramipril 1.25 mg orally once daily, titrate up to 5 mg once daily. ## Pediatric Dosing Established pediatric dosing varies by agent and indication. Consult specific product labeling or pediatric formularies. * **Hypertension:** * Enalapril: 0.08 mg/kg/day to 0.58 mg/kg/day orally, divided every 12-24 hours. Maximum dose generally 5 mg/kg/day or 40 mg/day. * Lisinopril: 0.07 mg/kg/day to 0.61 mg/kg/day orally, divided every 24 hours. Maximum dose generally 20 mg/day. ## Dose Adjustments * **Renal Impairment:** Reduce initial dose and titrate cautiously. Dose adjustments are specific to the agent and degree of renal impairment. For example, with significant renal impairment (CrCl < 30 mL/min), starting doses may be halved. * **Hepatic Impairment:** Use with caution. Dose adjustments are generally not routinely recommended but caution is advised due to potential for altered drug metabolism. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (particularly the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Serious:** Angioedema (including laryngeal edema, which can be fatal), acute kidney injury, hyperkalemia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction, especially in patients with volume depletion. * **Diuretics:** Increased risk of symptomatic hypotension, especially with thiazide diuretics. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid coadministration. * **ARBs:** Increased risk of hyperkalemia, renal dysfunction, and hypotension. Avoid coadministration in most cases. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly, especially after initiation or dose changes. * **Renal Function (Serum Creatinine, BUN):** Baseline and periodically, especially in patients with renal impairment, heart failure, or volume depletion. * **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment, diabetes, or those taking potassium-sparing agents. * **Angioedema Symptoms:** Educate patients to report immediately. ## Clinical Pearls * The characteristic dry cough is typically dose-related and often resolves after discontinuation. * Initiate at low doses and titrate slowly, particularly in patients who are volume depleted, elderly, or have renal impairment. * Monitor closely for signs of angioedema. Discontinue immediately if suspected. * ACE inhibitors are generally considered safe and effective in pregnancy after risk/benefit assessment, but should be avoided in the second and third trimesters due to risk of fetal harm. * Combination therapy with ARBs is generally not recommended due to increased risks without proven significant benefit in most populations. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines for complete details.*