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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, decreased aldosterone secretion, and reduced sympathetic nervous system activity, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Acute myocardial infarction (post-MI patients with evidence of LV dysfunction or heart failure) * Diabetic nephropathy (in patients with type 1 diabetes and hypertension) * Chronic kidney disease (in select patients to slow progression) ## Adult Dosing Dosing is highly individualized and titration is often required. The following are starting and maximum doses for common agents: * **Benazepril:** Start 10 mg once daily. Max 40 mg daily. * **Captopril:** Start 12.5 mg two to three times daily. Max 150 mg three times daily. * **Enalapril:** Start 5 mg once or twice daily. Max 40 mg daily. * **Fosinopril:** Start 10 mg once daily. Max 80 mg daily. * **Lisinopril:** Start 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 1 mg once daily. Max 4 mg daily. ## Pediatric Dosing ACE inhibitor use in pediatrics is less established than in adults. Dosing varies by agent and indication. * **Enalapril:** Hypertension: 0.07-0.1 mg/kg/dose every 24 hours, increased as needed. Max 0.61 mg/kg/day or 40 mg/day. * **Lisinopril:** Hypertension: 0.07-0.2 mg/kg/dose once daily. Max 20 mg/day. Consult pediatric-specific resources or guidelines for precise dosing. ## Dose Adjustments * **Renal Impairment:** Starting doses should be reduced, especially in patients with severe renal impairment (CrCl < 30 mL/min). Titration should be cautious. * **Hepatic Impairment:** Generally, no dose adjustment is needed, but caution is advised. * **Volume Depletion/Hyponatremia:** Initiate at a lower dose. * **Concomitant Diuretics:** May need to discontinue diuretic 2-3 days prior to ACE inhibitor initiation or start with a lower ACE inhibitor dose. ## 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 (Category D in 2nd and 3rd trimesters; Category C in 1st trimester). ## Adverse Effects * **Most Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, headache, fatigue. * **Serious:** Angioedema (can be fatal, especially involving the airway), acute kidney injury (especially in patients with bilateral renal artery stenosis), severe hypotension, hyperkalemia. * **Less Common:** Rash, dysgeusia, renal dysfunction, neutropenia, agranulocytosis, elevated liver enzymes. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) and Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs and COX-2 Inhibitors:** May blunt the antihypertensive effect and increase the risk of renal impairment. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concurrent use, especially in patients with diabetes or renal impairment. * **ARBs (Angiotensin II Receptor Blockers):** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concurrent use. * **Diuretics:** Increased risk of symptomatic hypotension. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels closely. * **mTOR Inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. ## Monitoring * **Renal Function:** Baseline and periodically, especially in patients with pre-existing renal disease, heart failure, or dehydration. Monitor serum creatinine and BUN. * **Electrolytes:** Baseline and periodically, especially serum potassium. Monitor more frequently in patients with renal impairment, diabetes, or those taking potassium supplements or potassium-sparing diuretics. * **Blood Pressure:** Regularly to assess efficacy and identify hypotension. * **Signs of Angioedema:** Educate patients to report swelling of the face, lips, tongue, or throat immediately. ## Clinical Pearls * The characteristic dry cough may occur weeks to months after starting therapy and can lead to discontinuation. It is reversible upon cessation of the drug. * Initiate with low doses and titrate slowly, especially in patients who are volume depleted, on diuretics, or have heart failure. * Monitor for first-dose hypotension, particularly in patients with heart failure or significant volume depletion. * ACE inhibitors are generally renoprotective in patients with diabetes and proteinuria. * While generally safe in pregnancy, they are contraindicated in the second and third trimesters due to the risk of fetal injury and death. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines before initiating or modifying drug therapy.