Ace%25252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing is highly variable by specific ACE inhibitor and indication. Titration is common. * **Hypertension:** Typical starting doses include benazepril 10 mg once daily, captopril 12.5 mg twice daily, enalapril 5 mg once daily, lisinopril 10 mg once daily, ramipril 2.5 mg once daily. Maximum doses vary but often range from 40 mg (benazepril, lisinopril), 50 mg TID (captopril), 20 mg BID (enalapril), to 10 mg once daily (ramipril). * **Heart Failure:** Typical starting doses include enalapril 2.5 mg twice daily, lisinopril 5 mg once daily, ramipril 1.25 mg once daily. Doses are titrated upwards based on tolerance and clinical response. Maximum doses often include enalapril 20 mg BID, lisinopril 35 mg once daily, ramipril 5 mg BID. * **Post-MI:** Typically initiated within 24 hours of stable MI. Doses vary by agent and patient stability, often aiming for doses used in heart failure. * **Diabetic Nephropathy:** Doses are titrated to achieve target blood pressure and reduce proteinuria, often using doses similar to hypertension or heart failure management. Specific dosing regimens are often guided by local protocols and individual patient response. ## Pediatric Dosing ACE inhibitors are used in pediatrics for hypertension and sometimes heart failure. Dosing is typically weight-based and requires careful titration. * **Hypertension:** * **Enalapril:** 0.07 mg/kg/day to 0.5 mg/kg/day divided BID. Maximum dose: 20 mg/day. * **Lisinopril:** 0.07 mg/kg/day once daily. Maximum dose: 20 mg/day. * **Captopril:** 0.3 mg/kg/dose to 0.5 mg/kg/dose TID. Maximum dose: 150 mg/day. Dosage in neonates and infants requires particular caution and may differ. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, especially in patients with significant renal impairment (CrCl < 30 mL/min). Monitor potassium closely. * **Hepatic Impairment:** No specific dose adjustment is usually required, but caution is advised due to potential for reduced drug clearance. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in volume-depleted or bilateral renal artery stenosis), hyperkalemia, neutropenia, hepatotoxicity (rare). ## Key Drug Interactions * **Potassium-sparing diuretics and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use, especially in patients with diabetes or renal impairment. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of renal impairment, hyperkalemia, and hypotension. Avoid dual blockade. ## Monitoring * **Baseline:** Renal function (serum creatinine, eGFR), electrolytes (especially potassium), blood pressure. * **During therapy:** * Renal function and potassium within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Blood pressure regularly. * Signs and symptoms of angioedema. * Complete blood count (CBC) if neutropenia is suspected. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and usually resolves upon discontinuation. * ACE inhibitors can cause a first-dose hypotensive effect, particularly in volume-depleted patients or those on diuretics. Consider initiating with a lower dose or holding diuretics prior to the first dose. * Risk of angioedema is higher in Black patients. * Always counsel patients on the potential for angioedema and to seek immediate medical attention if it occurs. * Avoid ACE inhibitors in patients with bilateral renal artery stenosis due to the risk of severe renal impairment. *** *This information is intended for educational purposes and does not substitute for professional medical advice. Always consult the most current prescribing information and your healthcare provider for definitive guidance.*