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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications primarily used to treat hypertension and heart failure by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation and reduced aldosterone secretion, resulting in lower blood pressure and decreased fluid retention. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Myocardial Infarction (post-MI management to reduce mortality and reinfarction) * Diabetic Nephropathy (proteinuria reduction) ## Adult Dosing Dosing varies significantly by specific ACE inhibitor. Doses are typically initiated low and titrated upwards based on patient response and tolerability. * **Lisinopril:** * Hypertension: 10 mg once daily, titrate up to 40 mg daily. Maximum: 40 mg daily. * Heart Failure: 5 mg once daily, titrate up to 40 mg daily. * Post-MI: 5 mg within 24 hours of symptom onset, then 5 mg daily for 6 days. * **Enalapril:** * Hypertension: 5 mg once or twice daily, titrate up to 40 mg daily (in divided doses). Maximum: 40 mg daily. * Heart Failure: 2.5 mg once or twice daily, titrate up to 20 mg twice daily. Maximum: 40 mg daily. * **Ramipril:** * Hypertension: 2.5 mg once daily, titrate up to 10 mg daily. Maximum: 10 mg daily. * Heart Failure: 1.25 mg once daily, titrate up to 10 mg daily. * Post-MI: 1.25 mg once daily, titrate up to 10 mg daily. * **Captopril:** * Hypertension: 25 mg twice or three times daily, titrate up to 150 mg three times daily. Maximum: 450 mg daily. * Heart Failure: 6.25 mg three times daily, titrate up to 50 mg three times daily. Maximum: 150 mg three times daily. *Note: Specific initiation and titration protocols may vary based on patient characteristics and institutional guidelines.* ## Pediatric Dosing Dosing for children is less standardized and often based on weight. * **Benazepril:** Hypertension: 0.1 mg/kg/day to 0.2 mg/kg/day once daily, maximum 20 mg/day. * **Enalapril:** Hypertension: 0.05 mg/kg/day to 0.1 mg/kg/day once daily, maximum 5 mg/day. For heart failure, higher doses may be used. * **Lisinopril:** Hypertension: 0.07 mg/kg/day once daily, maximum 20 mg/day. *Note: Pediatric dosing requires careful titration and frequent monitoring. Consult specific pediatric drug references for detailed guidance.* ## Dose Adjustments * **Renal Impairment:** Initiate with lower doses and titrate cautiously. Dose reduction may be necessary. * Captopril: If CrCl < 30 mL/min, start with 6.25 mg three times daily. * Lisinopril: If CrCl < 30 mL/min, start with 5 mg once daily. * Ramipril: If CrCl < 40 mL/min, start with 1.25 mg once daily. * **Hepatic Impairment:** Use with caution. Captopril and Enalapril are renally excreted, but hepatic metabolism can affect activity. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary angioedema. * Concomitant use with aliskiren in patients with diabetes. * Pregnancy (especially during the second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hypotension, hyperkalemia. * **Serious:** Angioedema (including laryngeal edema), acute kidney injury, neutropenia, hepatotoxicity. ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone) and potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 inhibitors:** May blunt antihypertensive effect and increase risk of renal impairment. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concomitant use, especially in patients with diabetes. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of hypotension, hyperkalemia, and renal dysfunction. Avoid concomitant use. * **Diuretics:** Increased risk of symptomatic hypotension. ## Monitoring * **Blood Pressure:** Regularly monitor BP at home and in clinic. * **Renal Function:** Monitor serum creatinine and BUN, especially at initiation and dose changes. * **Electrolytes:** Monitor serum potassium, particularly in patients with renal impairment, diabetes, or those taking potassium supplements or potassium-sparing diuretics. * **Signs/Symptoms of Angioedema:** Educate patients to report immediately. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels and is typically dose-dependent and reversible upon discontinuation. * Initiate at low doses and titrate slowly, especially in patients with volume depletion, hyponatremia, severe heart failure, or renal impairment. * ACE inhibitors are generally safe and effective in most patients with hypertension and heart failure, but careful monitoring is crucial. * Consider switching to an Angiotensin II Receptor Blocker (ARB) if cough is intolerable or angioedema occurs, though cross-reactivity can occur. *** *Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient safety.*