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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of medications primarily used to treat hypertension and heart failure. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation and reduced blood pressure. ## Primary Indications * Hypertension * Heart Failure (reduced ejection fraction) * Left Ventricular Dysfunction post-Myocardial Infarction * Diabetic Nephropathy * Proteinuric Chronic Kidney Disease ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor and indication. Titration is key. * **Hypertension:** * Benazepril: Start 10 mg once daily, max 40 mg/day. * Captopril: Start 25 mg twice daily, max 150 mg twice daily. * Enalapril: Start 5 mg once daily, max 40 mg/day. * Fosinopril: Start 10 mg once daily, max 80 mg/day. * Lisinopril: Start 10 mg once daily, max 40 mg/day. * Moexipril: Start 7.5 mg once daily, max 30 mg/day. * Perindopril: Start 2.5-5 mg once daily, max 10 mg/day. * Ramipril: Start 2.5 mg once daily, max 10 mg/day. * Trandolapril: Start 1 mg once daily, max 8 mg/day. * Quinapril: Start 10 mg twice daily, max 80 mg/day. * **Heart Failure:** Doses often higher than for hypertension and require careful titration. * Enalapril: Start 5 mg once or twice daily, target 10 mg twice daily, max 20 mg twice daily. * Lisinopril: Start 2.5-5 mg once daily, target 10 mg once daily, max 40 mg once daily. * Ramipril: Start 2.5 mg once daily, target 5 mg once daily, max 10 mg once daily. * **Post-MI/LV Dysfunction:** * Lisinopril: Start 5 mg once daily, target 10 mg once daily. * Ramipril: Start 2.5 mg twice daily, target 5 mg twice daily, max 10 mg twice daily. ## Pediatric Dosing Dosing in pediatric patients is less standardized and often based on weight. Consult specific pediatric guidelines. * **Hypertension:** * Enalapril: 0.07 to 0.1 mg/kg/dose once daily, max 0.61 mg/kg/day (or 40 mg/day if lower). * Lisinopril: 0.07 to 0.2 mg/kg/dose once daily, max 20 mg/day. * Ramipril: 0.05 mg/kg/dose once daily, max 2.5 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is typically required for moderate to severe renal impairment (CrCl < 30 mL/min). Specific recommendations vary by drug and CrCl. * **Hepatic Impairment:** Caution and potential dose reduction for drugs with significant first-pass metabolism (e.g., enalapril, moexipril). ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (especially in the second and third trimesters). * Hypersensitivity to ACE inhibitors. ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Less Common/Serious:** Angioedema (can be life-threatening), acute kidney injury (especially in bilateral renal artery stenosis), rash, elevated liver enzymes, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics, Potassium Supplements, Aldosterone Antagonists, ARBs, Aliskiren:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in patients with volume depletion or underlying renal disease. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. Monitor lithium levels. * **Diuretics (especially potent ones like loop diuretics):** Increased risk of symptomatic hypotension, particularly after initiation. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During Therapy:** * Renal function (serum creatinine) and electrolytes (potassium) within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Blood pressure. * Signs and symptoms of angioedema or other hypersensitivity reactions. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation and typically resolves upon discontinuation. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, elderly, or have renal impairment. * Discontinue immediately if angioedema occurs and do not rechallenge. * Caution with concomitant use of ARBs or aliskiren due to increased risk of hyperkalemia and renal impairment. *** *This information is intended for healthcare professionals. Always consult the official prescribing information and local guidelines for the most up-to-date and complete drug information.*