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# ACE Inhibitors ## Overview ACE inhibitors (Angiotensin-Converting Enzyme 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 aldosterone secretion, which lowers blood pressure and reduces cardiac workload. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Post-myocardial infarction (to improve survival) * Diabetic nephropathy (to slow progression) * Chronic kidney disease (in certain populations) ## Adult Dosing * **Hypertension:** Initial doses vary by agent, e.g., lisinopril 10 mg PO once daily, enalapril 5 mg PO once or twice daily, ramipril 2.5 mg PO once daily. Doses are typically titrated every 1-4 weeks based on BP response. Maximum doses also vary by agent (e.g., lisinopril 40 mg/day, enalapril 40 mg/day, ramipril 10 mg/day). * **Heart Failure:** Initial doses are usually lower than for hypertension to assess tolerability, e.g., lisinopril 2.5-5 mg PO once daily, enalapril 2.5 mg PO twice daily, captopril 6.25 mg PO three times daily. Doses are titrated upwards over weeks to months as tolerated, aiming for target doses (e.g., lisinopril 32.5 mg/day, enalapril 20 mg/day, captopril 150 mg/day). * **Post-MI:** Typically initiated within 24 hours of MI if no contraindications exist. Dosing follows similar principles to heart failure treatment. ## Pediatric Dosing * **Hypertension:** Generally initiated at lower doses and titrated based on BP response. Specific starting doses and titration schedules vary by age group and agent. For example, enalapril can be initiated at 0.07 mg/kg/day (PO) divided BID in children >1 month old. Dosing should be guided by current pediatric guidelines and institutional protocols. * **Other indications:** Use in pediatrics for heart failure or post-MI is less established and should be based on specialist consultation and available evidence. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary, particularly for agents renally eliminated. CrCl <30 mL/min often requires significant dose reduction or avoidance of certain agents. Consult specific drug monographs. * **Hepatic Impairment:** Caution is advised, particularly with prodrugs like enalapril and ramipril. Dose adjustments may be needed. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment * Concomitant use with aliskiren in patients with diabetes or renal impairment * Pregnancy (especially second and third trimesters) * Hypersensitivity to the specific ACE inhibitor * Bilateral renal artery stenosis (relative contraindication, risk of precipitating renal failure) ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, fatigue, hyperkalemia, hypotension. * **Serious:** Angioedema (can be life-threatening, involves face, lips, tongue, larynx), acute kidney injury (especially in susceptible individuals), neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive efficacy and increase risk of renal impairment, especially in elderly or volume-depleted patients. * **Aliskiren:** Increased risk of hypotension, hyperkalemia, and renal dysfunction. Avoid concomitant use, especially in diabetes. * **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity. Monitor lithium levels closely. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * **Blood Pressure:** Regularly monitor BP response to therapy. * **Renal Function:** Baseline and periodic monitoring of serum creatinine and BUN. * **Electrolytes:** Baseline and periodic monitoring of potassium. * **Angioedema:** Educate patients on signs/symptoms and to seek immediate medical attention. ## Clinical Pearls * The characteristic dry cough is thought to be due to bradykinin accumulation. If cough is bothersome, consider switching to an ARB. * Initiate at low doses and titrate slowly, especially in patients who are volume-depleted, elderly, or have impaired renal function. * First-dose hypotension can occur, particularly in patients taking diuretics. Consider holding diuretics prior to initiating ACE inhibitor or starting at a lower dose. * Use with caution in patients with a history of angioedema from other causes. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. This information is intended for healthcare professionals. Please verify current prescribing information for specific agents and patient populations.