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# ACE Inhibitors ## Overview Angiotensin-converting enzyme (ACE) 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 blood pressure. ## Primary Indications * Hypertension * Heart failure (systolic dysfunction) * Myocardial infarction (post-MI management) * Diabetic nephropathy * Chronic kidney disease (certain types) ## Adult Dosing Dosing varies significantly by agent and indication. Doses should be started low and titrated up based on patient response and tolerability. * **Hypertension:** Initial doses vary (e.g., lisinopril 10 mg once daily, enalapril 5 mg once or twice daily, ramipril 2.5 mg once daily). Maximum doses vary by agent (e.g., lisinopril up to 40 mg once daily, enalapril up to 40 mg once or twice daily, ramipril up to 10 mg once daily). * **Heart Failure:** Initial doses are typically lower than for hypertension to minimize risk of hypotension and renal dysfunction (e.g., lisinopril 2.5-5 mg once daily, enalapril 2.5 mg twice daily, ramipril 1.25-2.5 mg once daily). Titration aims for target doses proven in clinical trials, which may be higher (e.g., lisinopril 32.5 mg once daily, enalapril 10 mg twice daily, ramipril 5 mg twice daily), but often lower doses are sufficient and better tolerated. * **Post-MI:** Similar to heart failure, initiated cautiously. * **Diabetic/Chronic Kidney Disease:** Dosing is often based on achieving target blood pressure and proteinuria reduction. ## Pediatric Dosing Dosing is based on body weight and indication. Specific protocols or pharmacist consultation may be necessary. * **Hypertension:** * Enalapril: 0.1 mg/kg/dose to 0.5 mg/kg/day divided every 12-24 hours. Maximum dose typically 20 mg/day. * Lisinopril: 0.07 mg/kg/dose to 0.2 mg/kg/day divided once daily. Maximum dose typically 20 mg/day. * Ramipril: 0.05 mg/kg/dose to 0.25 mg/kg/day divided once daily. Maximum dose typically 5 mg/day. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific guidelines vary by agent and creatinine clearance. Monitor serum creatinine and potassium closely. * **Hepatic Impairment:** Generally no dose adjustment needed, but caution is advised due to potential for hepatic events. * **Volume Depletion:** Initiate at lower doses and titrate cautiously due to risk of hypotension. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment. * Concomitant use with aliskiren in patients with diabetes. * Second or third trimester of pregnancy (teratogenic). * Hypersensitivity to the drug. * History of hereditary or idiopathic angioedema. ## Adverse Effects * Cough (dry, persistent) - most common * Dizziness, lightheadedness, hypotension * Hyperkalemia * Angioedema (rare but life-threatening, can occur at any time) * Acute kidney injury (especially in susceptible individuals) * Fatigue * Rash * Dysgeusia (altered taste) ## Key Drug Interactions * **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, aliskiren, ARBs:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in volume-depleted patients. * **Lithium:** Increased serum lithium levels and risk of toxicity. * **Diuretics (thiazide, loop):** Additive hypotensive effect, increased risk of renal dysfunction and symptomatic hypotension. * **mTOR inhibitors (e.g., sirolimus, everolimus):** Increased risk of angioedema. ## Monitoring * Blood pressure (prior to and after dose changes) * Serum creatinine and electrolytes (especially potassium) at baseline, within 1-2 weeks of initiation or dose increase, and periodically thereafter. * Renal function in patients with risk factors. * Signs and symptoms of angioedema and cough. ## Clinical Pearls * Cough is usually dose-related and often resolves upon discontinuation. Consider switching to an ARB if cough is bothersome. * Angioedema is a medical emergency; discontinue immediately and do not re-challenge. * Initiate at the lowest effective dose, especially in the elderly, volume-depleted, or renally impaired patients. * ACE inhibitors are generally contraindicated in pregnancy, particularly in the second and third trimesters. *** *This information is intended for clinical use and does not substitute for comprehensive drug reference material. Always verify current prescribing information with the official product monograph or a trusted drug information resource before initiating or modifying therapy.*