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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, resulting in lower blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (proteinuric) * Chronic kidney disease (proteinuric) ## Adult Dosing Dosing is highly individualized and depends on the specific agent and indication. Typical starting doses are low and titrated upwards. * **Hypertension:** * Benazepril: Start 10 mg once daily, titrate up to 40 mg daily. * Captopril: Start 25 mg twice daily, titrate up to 50 mg three times daily. * Enalapril: Start 5 mg once daily, titrate up to 20 mg twice daily. * Fosinopril: Start 10 mg once daily, titrate up to 40 mg daily. * Lisinopril: Start 10 mg once daily, titrate up to 40 mg daily. * Moexipril: Start 7.5 mg once daily, titrate up to 30 mg daily. * Perindopril: Start 2.5-5 mg once daily, titrate up to 10 mg daily. * Quinapril: Start 10 mg twice daily, titrate up to 20 mg twice daily. * Ramipril: Start 2.5 mg once daily, titrate up to 10 mg daily. * Trandolapril: Start 1 mg once daily, titrate up to 4 mg daily. * **Heart Failure:** Doses are typically higher than for hypertension. Refer to specific guidelines or product monographs. * **Post-MI/Diabetic Nephropathy/CKD:** Doses are also specific to indication and agent. ## Pediatric Dosing Dosing in pediatric patients is less established and should be individualized based on weight, renal function, and clinical response. Consult pediatric-specific resources. * **Hypertension:** * Enalapril: Start 0.07 mg/kg once daily (max 5 mg/day), titrate up to 0.42 mg/kg/day (max 40 mg/day). * Lisinopril: Start 0.07 mg/kg once daily (max 10 mg/day), titrate up to 0.61 mg/kg/day (max 40 mg/day). ## Dose Adjustments * **Renal Impairment:** Dose reduction is often required, especially in moderate to severe impairment (e.g., CrCl < 30 mL/min). Specific recommendations vary by drug. * **Hepatic Impairment:** Caution is advised; dose adjustment may be needed for some agents (e.g., captopril, enalapril). ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus. * Pregnancy (especially second and third trimesters, as they can cause fetal injury or death). ## Adverse Effects * **Common:** Dry cough, dizziness, fatigue, headache, hyperkalemia. * **Serious:** Angioedema (facial, limb, intestinal), acute kidney injury (especially in renal artery stenosis), hypotension, hyperkalemia, neutropenia (rare). ## Key Drug Interactions * **Potassium-sparing diuretics (e.g., spironolactone, amiloride), potassium supplements, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs (including COX-2 inhibitors):** May decrease antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients or those with pre-existing renal disease. * **Diuretics:** Additive hypotensive effect. Risk of profound hypotension, especially with thiazides, if diuretic therapy is not stopped or dose reduced prior to ACE inhibitor initiation. * **Lithium:** Reduced lithium clearance, leading to increased serum lithium levels and risk of toxicity. * **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid in patients with diabetes. ## Monitoring * **Baseline:** Blood pressure, serum potassium, serum creatinine, BUN. * **During therapy:** Blood pressure, serum potassium, serum creatinine, BUN (especially after dose increases or in patients with risk factors for renal impairment). Monitor for cough and angioedema. ## Clinical Pearls * ACE inhibitors are generally renoprotective in proteinuric kidney disease. * The characteristic dry cough is thought to be due to bradykinin accumulation and is reversible upon discontinuation. * Initiate at low doses, particularly in the elderly, volume-depleted patients, or those with heart failure or renal impairment. * Risk of angioedema is higher in Black patients. * Monitor closely for hyperkalemia, especially in patients with renal impairment or those taking potassium-sparing agents. * Discontinue immediately if angioedema occurs. *** *Disclaimer: This information is intended for clinical use and is not a substitute for professional medical advice. Always verify current prescribing information with the manufacturer's product monograph and consult relevant clinical practice guidelines.*