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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and decreased aldosterone secretion. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuric kidney disease) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor and indication. Titration is usually required. * **Hypertension:** * Benazepril: Start at 5-10 mg once daily. Max: 40 mg daily. * Captopril: Start at 6.25-12.5 mg two to three times daily. Max: 150 mg three times daily. * Enalapril: Start at 5 mg once daily. Max: 40 mg daily. * Lisinopril: Start at 10 mg once daily. Max: 40 mg daily. * Ramipril: Start at 2.5 mg once daily. Max: 10 mg daily. * *Other agents available with similar dosing principles.* * **Heart Failure:** * Enalapril: Start at 2.5 mg twice daily. Titrate up as tolerated. Max: 10 mg twice daily. * Lisinopril: Start at 5 mg once daily. Titrate up as tolerated. Max: 35 mg once daily. * Ramipril: Start at 1.25-2.5 mg once daily. Titrate up as tolerated. Max: 10 mg once daily. * **Post-MI:** Typically initiated within 24 hours if no contraindications. Dosing follows guidelines for heart failure or hypertension, with titration guided by patient tolerance and clinical response. * **Diabetic Nephropathy:** Dosing often similar to hypertension, aiming for target blood pressure. ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and heart failure. Dosing is weight-based and requires careful titration. * **Hypertension:** * Enalapril: 0.07-0.1 mg/kg/dose once daily, may increase to twice daily. Max: 0.61 mg/kg/day or 40 mg/day. * Lisinopril: 0.07-0.2 mg/kg/dose once daily. Max: 20 mg/day for children < 6 years; 40 mg/day for children ≥ 6 years. * *Captopril dosing also available, typically multiple doses per day.* * **Heart Failure:** Dosing is less established and often requires specialist management. ## Dose Adjustments * **Renal Impairment:** Reduce dose and titrate cautiously, especially in patients with severe renal impairment. Initial doses may need to be lower. * **Hepatic Impairment:** Captopril and enalapril (prodrug) may require dose reduction. ## 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), hyperkalemia, dizziness, fatigue, hypotension. * **Serious:** Angioedema (can be life-threatening), acute kidney injury, hyperkalemia, neutropenia, hepatotoxicity (rare). ## Key Drug Interactions * **Potassium-sparing diuretics & Potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs & Aspirin:** May reduce antihypertensive effect and increase risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Contraindicated in patients with diabetes or renal impairment. * **ARBs:** Increased risk of hyperkalemia, angioedema, and renal dysfunction. * **Lithium:** Increased lithium levels and risk of toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During Therapy:** * Renal function (creatinine) and electrolytes (potassium) within 1-2 weeks of initiation or dose change, and periodically thereafter. * Blood pressure regularly. * Monitor for signs/symptoms of angioedema or other hypersensitivity reactions. * Consider baseline and periodic complete blood count (CBC) in specific populations (e.g., collagen vascular disease, renal transplant). ## Clinical Pearls * Cough is a common, dose-limiting side effect, often resolving upon discontinuation. Angioedema is a medical emergency. * Initiate at a low dose and titrate slowly, especially in patients who are volume-depleted, have heart failure, or impaired renal function. * First-dose hypotension can occur, particularly in patients with high renin states (e.g., severe heart failure, diuretic use). * ACE inhibitors are generally not recommended in pregnancy due to potential fetal harm. *** *This information is for educational purposes only and does not substitute for professional medical advice. Always consult with a qualified healthcare provider to determine the best course of treatment for your specific condition and to ensure you have the most up-to-date prescribing information.*