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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications that block the action of the angiotensin-converting enzyme, which plays a role in blood pressure regulation. They are widely used for cardiovascular conditions. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI, to improve survival) * Diabetic nephropathy * Proteinuric kidney disease ## Adult Dosing Dosing varies significantly by agent and indication. Titration is generally recommended. * **Hypertension:** Typical starting doses are low and titrated upwards every 2-4 weeks. Common starting doses: * Lisinopril: 10 mg PO daily * Enalapril: 5 mg PO daily or BID * Ramipril: 2.5 mg PO daily * Benazepril: 10 mg PO daily * Maximum doses vary by agent, e.g., Lisinopril up to 40 mg daily, Enalapril up to 40 mg daily. * **Heart Failure:** Usually initiated at a lower dose than for hypertension and titrated more slowly. * Lisinopril: Start at 2.5-5 mg PO daily, titrate up to target dose (often 20 mg PO daily). * Enalapril: Start at 2.5-5 mg PO BID, titrate up to target dose (often 10 mg PO BID). * Ramipril: Start at 1.25-2.5 mg PO daily, titrate up to target dose (often 10 mg PO daily). * **Post-Myocardial Infarction:** * Lisinopril: Start 5 mg PO daily, can increase to 10 mg PO daily after 24 hours. * Ramipril: Start 1.25 mg PO daily, titrate up to 5 mg PO BID if tolerated. ## Pediatric Dosing Established pediatric dosing varies by agent and indication. Consult specific product information or pediatric guidelines. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/dose PO BID (maximum 0.5 mg/kg/day or 20 mg/day). * Lisinopril: 0.07-0.2 mg/kg/dose PO daily (maximum 20 mg/day). * **Heart Failure:** Generally not recommended in infants and young children unless initiated by a pediatric cardiologist. ## Dose Adjustments * **Renal Impairment:** Dose reduction is typically required, especially in moderate to severe renal impairment (CrCl < 30 mL/min). Specific reductions depend on the agent and degree of impairment. * **Hepatic Impairment:** Enalapril dose should be reduced in severe hepatic impairment. Other agents generally do not require dose adjustment, 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 mellitus or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Angioedema:** Potentially life-threatening. More common in Black patients. * **Cough:** Dry, persistent cough (non-productive) is common. * **Hyperkalemia:** Especially in patients with renal impairment or those taking potassium-sparing diuretics or potassium supplements. * **Hypotension:** Particularly with the first dose or in volume-depleted patients. * **Renal dysfunction:** Can worsen renal function, especially in patients with bilateral renal artery stenosis. * **Dizziness, fatigue, headache.** * **Rash.** ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride), potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May decrease antihypertensive effect and increase risk of renal impairment, particularly in elderly or volume-depleted patients. * **Diuretics (especially loop and thiazide):** Increased risk of hypotension and azotemia. * **Lithium:** Increased lithium levels and toxicity. * **Aliskiren:** Increased risk of hypotension, hyperkalemia, and renal dysfunction. Avoid concomitant use in patients with diabetes or renal impairment. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly, especially after initiating therapy or dose changes. * **Renal Function:** Serum creatinine and BUN, particularly at baseline, with dose adjustments, and in patients with risk factors for renal impairment. * **Potassium:** Serum potassium at baseline, with dose adjustments, and in patients with risk factors for hyperkalemia. * **Angioedema:** Monitor for signs and symptoms (swelling of face, lips, tongue, throat, extremities; difficulty breathing). ## Clinical Pearls * ACE inhibitors are renoprotective in patients with diabetes and proteinuria. * Discontinue ACE inhibitors immediately if angioedema is suspected. * Initiate at low doses and titrate slowly, especially in the elderly, volume-depleted, or renally impaired. * Advise patients to report cough or signs of angioedema. * Monitor for hyperkalemia, particularly in patients with renal insufficiency or those on potassium-sparing agents. *** *This information is intended for clinical decision support and does not replace professional medical advice. Always consult current prescribing information and relevant guidelines for the most up-to-date and specific recommendations.*