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# ACE Inhibitors ## Overview ACE inhibitors (ACEIs) are a class of medications that block the action of angiotensin-converting enzyme, leading to vasodilation and reduced sodium and water retention. This results in a decrease in blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (MI) for specific patients * Diabetic nephropathy * Proteinuric chronic kidney disease ## Adult Dosing Dosing varies significantly by specific ACEI agent. Typical starting doses and maximum doses are provided below for common agents. Titration is guided by patient response and tolerability. * **Benazepril:** Start 5-10 mg once daily. Max 40 mg daily. * **Captopril:** Start 12.5-25 mg twice daily. Max 150 mg twice daily. (More frequent dosing due to shorter half-life). * **Enalapril:** Start 2.5-5 mg once or twice daily. Max 40 mg daily. * **Fosinopril:** Start 10 mg once daily. Max 80 mg daily. * **Lisinopril:** Start 5-10 mg once daily. Max 40 mg daily. * **Moexipril:** Start 7.5 mg once daily. Max 30 mg daily. * **Perindopril:** Start 2.5-5 mg once daily. Max 10 mg daily. * **Quinapril:** Start 5-10 mg twice daily. Max 80 mg daily. * **Ramipril:** Start 2.5 mg once daily. Max 10 mg daily. * **Trandolapril:** Start 0.5-1 mg once daily. Max 4 mg daily. ## Pediatric Dosing Dosing for pediatric patients is less standardized and often based on weight. * **Enalapril:** 0.07 mg/kg/day to 0.5 mg/kg/day divided once or twice daily. Max dose is agent-specific and may be capped at adult maximums. * **Lisinopril:** 0.07 mg/kg/day to 0.61 mg/kg/day once daily. Max dose is agent-specific and may be capped at adult maximums. * **Ramipril:** 0.05 mg/kg/day to 0.1 mg/kg/day once daily. Max dose is agent-specific and may be capped at adult maximums. Dosing for other agents is available but less commonly used or studied in pediatrics. Consult specific pediatric guidelines. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly with lower GFR. Specific recommendations vary by agent and degree of renal impairment. For example, lisinopril 10 mg daily is often the maximum in severe renal impairment (CrCl < 30 mL/min). * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. Captopril and enalapril may require lower doses. ## Contraindications * History of angioedema related to previous ACEI therapy. * Concomitant use with aliskiren in patients with diabetes mellitus. * Concomitant use with sacubitril/valsartan (wait at least 36 hours after stopping ACEI before initiating). * Pregnancy (Category D in 2nd and 3rd trimesters, Category C in 1st trimester). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (rare but potentially life-threatening), acute kidney injury (especially in patients with bilateral renal artery stenosis or severe heart failure), hypotension, hyperkalemia, rash. ## Key Drug Interactions * **Potassium-sparing diuretics & Potassium supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Contraindicated in diabetes. * **ARBs:** Increased risk of hyperkalemia and angioedema. Generally avoid concomitant use. * **Sacubitril/Valsartan:** Increased risk of angioedema. Contraindicated. * **Lithium:** ACEIs can increase lithium levels, leading to toxicity. Monitor lithium levels closely. ## Monitoring * **Blood Pressure:** Regularly monitor to assess efficacy and identify hypotension. * **Renal Function (Serum Creatinine & BUN):** Baseline and periodically, especially with risk factors for renal impairment. * **Serum Potassium:** Baseline and periodically, especially in patients with renal impairment, diabetes, or those taking potassium-sparing agents. * **Angioedema:** Patient education on signs and symptoms is crucial. ## Clinical Pearls * Cough is a common dose-limiting side effect, occurring in up to 20% of patients. If cough is bothersome, consider switching to an ARB. * Start at low doses and titrate slowly, especially in patients who are volume-depleted, salt-depleted, or have heart failure. * ACEIs are renoprotective in patients with diabetes and proteinuria. * Do not co-administer with sacubitril/valsartan or aliskiren in diabetics. *** *This information is intended for clinical pharmacists and healthcare professionals. Always consult the most current prescribing information and relevant guidelines for complete details.*