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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs 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 (systolic dysfunction) * Post-Myocardial Infarction (for patients with evidence of LV dysfunction or heart failure) * Diabetic Nephropathy (in select patients with diabetes and proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is typically done every 1-4 weeks. * **Benazepril:** Start 5-10 mg once daily. Max 40 mg once daily. * **Captopril:** Start 25 mg BID-TID. Max 150 mg TID. * **Enalapril:** Start 5 mg once daily (oral). Max 40 mg once daily. (IV: 1.25 mg IV q6h, max 5 mg q6h). * **Fosinopril:** Start 10 mg once daily. Max 80 mg once daily. * **Lisinopril:** Start 10 mg once daily. Max 40 mg once daily. * **Moexipril:** Start 7.5 mg once daily. Max 30 mg once daily. * **Perindopril:** Start 5 mg once daily. Max 10 mg once daily. * **Quinapril:** Start 10 mg once daily. Max 80 mg once daily. * **Ramipril:** Start 2.5 mg once daily. Max 10 mg once daily. * **Trandolapril:** Start 1 mg once daily. Max 4 mg once daily. ## Pediatric Dosing Dosing varies by age and indication. Specific protocols may be necessary. * **Enalapril:** Hypertension: 6 months to <16 years: 0.05-0.2 mg/kg/day divided q12-24h. Max 0.6 mg/kg/day or 40 mg/day. * **Lisinopril:** Hypertension: 6 to 16 years: 0.07 mg/kg/day once daily. Max 20 mg/day. * **Ramipril:** Hypertension: Not established in children <10 years. For 10-16 years: 1.25-5 mg once daily. Max 5 mg/day. ## Dose Adjustments * **Renal Impairment:** Initiate at lower doses and titrate cautiously. Dose adjustments are often needed, particularly for enalapril and lisinopril when CrCl < 30 mL/min. Captopril and fosinopril may require less dose adjustment. * **Hepatic Impairment:** Use with caution. No specific dose adjustments are generally recommended, but monitor for increased serum concentrations and adverse effects. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes or renal impairment. * Pregnancy (especially second and third trimesters). ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, headache, hyperkalemia, hypotension. * **Less Common:** Angioedema (facial, lingual, laryngeal), rash, dysgeusia, acute kidney injury, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, Potassium supplements, Aldosterone antagonists, ARBs, NSAIDs:** Increased risk of hyperkalemia. * **Diuretics (especially thiazides and loop diuretics):** Increased risk of hypotension, particularly symptomatic hypotension. Initiating ACE inhibitors at lower doses and/or adding a diuretic before starting an ACE inhibitor can minimize this risk. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to increased lithium toxicity. Monitor lithium levels closely. * **mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Avoid concomitant use; risk of angioedema is significantly increased. A 36-hour washout period is required after stopping an ACE inhibitor before starting sacubitril/valsartan. ## Monitoring * **Blood Pressure:** Regularly monitor for therapeutic effect and hypotension. * **Renal Function:** Monitor serum creatinine and BUN, especially in patients with pre-existing renal disease, heart failure, or renovascular hypertension. * **Potassium:** Monitor serum potassium levels, especially in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics. * **Angioedema:** Educate patients about the signs and symptoms and instruct them to discontinue the drug immediately if they occur. * **Cough:** Assess for persistent cough. ## Clinical Pearls * The characteristic dry cough is thought to be due to increased bradykinin levels. If cough is bothersome, consider switching to an Angiotensin II Receptor Blocker (ARB). * Hypotension is more likely with the first dose, in patients with volume depletion, or those on diuretics. Consider a lower starting dose and/or temporary discontinuation of diuretics. * ACE inhibitors can cause significant fetal harm and are contraindicated in pregnancy. * Monitor for signs of hyperkalemia, particularly in patients with renal impairment or those on concomitant potassium-increasing agents. * Dosing needs to be individualized and titrated based on patient response and tolerability. *** *Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for the specific drug and patient scenario.*