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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications that block the production of angiotensin II, a potent vasoconstrictor, leading to vasodilation and decreased blood pressure. They also reduce aldosterone secretion, promoting sodium and water excretion. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (MI) with evidence of left ventricular dysfunction * Diabetic nephropathy (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is generally required. * **Hypertension:** Common starting doses include: * Lisinopril: 10 mg once daily * Enalapril: 5 mg once or twice daily * Ramipril: 2.5 mg once daily * Benazepril: 10 mg once daily * Captopril: 12.5 mg twice daily * *Maximum doses vary by agent, often ranging from 40 mg to 80 mg daily.* * **Heart Failure:** Common starting doses include: * Lisinopril: 5 mg once daily * Enalapril: 2.5 mg once or twice daily * Ramipril: 2.5 mg twice daily * Captopril: 6.25 mg three times daily * *Target doses are often higher and based on clinical response and tolerability, e.g., Lisinopril up to 40 mg daily, Enalapril up to 20 mg twice daily.* * **Post-MI:** Usually initiated within 24 hours if no contraindications exist. * Lisinopril: 5 mg, followed by 10 mg daily. * Enalapril: 2.5 mg, followed by 5 mg twice daily. * *Titration to target doses similar to heart failure therapy.* * **Diabetic Nephropathy:** * Lisinopril: 10 mg once daily. * Enalapril: 10 mg once daily. * Ramipril: 5 mg once daily. * *Titration to achieve maximum proteinuria reduction, e.g., Lisinopril up to 20 mg daily, Ramipril up to 10 mg daily.* ## Pediatric Dosing Established pediatric dosing varies by agent and indication. * **Hypertension:** * **Enalapril:** 6 months to 16 years: 0.08 mg/kg/day to 0.5 mg/kg/day divided once or twice daily. Max: 40 mg/day. * **Lisinopril:** 6 years to 16 years: 0.07 mg/kg/day to 5 mg/day divided once daily. Max: 40 mg/day. * *Dosing for other ACE inhibitors in pediatric populations may be less established or based on off-label use. Consult specific pediatric guidelines.* ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly for agents primarily renally eliminated. Cautious titration is essential. Specific reductions depend on the agent and creatinine clearance (CrCl). For example, with Lisinopril: CrCl < 30 mL/min/1.73 m², start with 5 mg daily; CrCl 30-80 mL/min/1.73 m², start with 10 mg daily. * **Hepatic Impairment:** Generally requires cautious initiation and titration; however, dose adjustments are not always strictly defined and depend on the individual's response. ## 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 (Category D). * Hypersensitivity to ACE inhibitors. ## Adverse Effects * **Common:** Cough (dry, persistent), hyperkalemia, dizziness, hypotension, fatigue, headache. * **Less Common/Serious:** Angioedema (potentially life-threatening), acute kidney injury (especially in susceptible individuals), rash, dysgeusia, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics / Potassium Supplements / Salt Substitutes:** Increased risk of severe hyperkalemia. Monitor potassium closely. * **Diuretics (Thiazide and Loop):** Increased risk of hypotension, particularly with the first dose. Consider holding diuretic or starting ACE inhibitor at a lower dose. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in volume-depleted patients or those with pre-existing renal disease. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels. * **ARBs / Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concurrent use, especially in high-risk patients. * **mTOR Inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, serum potassium, serum creatinine, renal function (eGFR). * **During Therapy:** * Blood pressure regularly. * Serum potassium and creatinine within 1-2 weeks of initiation or dose change, and periodically thereafter (frequency guided by patient factors, e.g., renal impairment, hyperkalemia risk). * Monitor for signs and symptoms of angioedema and cough. ## Clinical Pearls * Cough is a common, dose-dependent side effect and often leads to discontinuation. If cough occurs, consider switching to an Angiotensin II Receptor Blocker (ARB). * First-dose hypotension can occur, especially in patients who are volume-depleted or on diuretics. Administer the first dose under medical supervision if possible. * Angioedema is a medical emergency; discontinue immediately and manage airway. * ACE inhibitors are generally renoprotective in proteinuric diabetic kidney disease. * Monitor for signs of hyperkalemia (muscle weakness, paresthesias, cardiac arrhythmias). * Dosing and titration should be guided by individual patient response and tolerability. *** **Disclaimer:** This information is intended for educational purposes and is not a substitute for professional medical advice. Always consult the most current prescribing information and guidelines for specific patient management.