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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, reduced aldosterone secretion, and decreased sympathetic nervous system activity. ## Primary Indications * Hypertension * Heart failure (reduced ejection fraction) * Post-myocardial infarction (left ventricular dysfunction) * Diabetic nephropathy (proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is typically guided by blood pressure and tolerability. * **Hypertension:** Initial doses vary by agent (e.g., lisinopril 5-10 mg PO daily, enalapril 5 mg PO daily, ramipril 2.5 mg PO daily). Usual maintenance doses range from 10-40 mg daily for lisinopril, 10-40 mg daily for enalapril, and 5-10 mg daily for ramipril. Maximum doses vary by agent and should not be exceeded without careful consideration of risk-benefit. * **Heart Failure:** Initial doses are often lower than for hypertension to minimize risk of hypotension and renal dysfunction (e.g., enalapril 2.5 mg PO BID, lisinopril 5 mg PO daily, ramipril 1.25 mg PO daily). Titration aims for target doses or maximally tolerated doses (e.g., enalapril 10-20 mg PO BID, lisinopril 20-40 mg PO daily, ramipril 5 mg PO BID). * **Post-MI:** Similar to heart failure dosing, initiated early after MI in eligible patients (e.g., captopril 6.25 mg PO TID, lisinopril 5 mg PO daily). Titration aims for target doses. * **Diabetic Nephropathy:** Specific agents and doses may be preferred based on evidence (e.g., ramipril 5 mg PO daily, perindopril 5 mg PO daily). ## Pediatric Dosing ACE inhibitors are used in pediatric patients for hypertension and certain cardiac conditions. Dosing is typically weight-based and requires careful titration. * **Hypertension:** For example, enalapril: 0.08 mg/kg/day to 0.58 mg/kg/day PO divided BID. Maximum dose is typically 5 mg/kg/day or 40 mg/day, whichever is less. * **Heart Failure:** Enalapril: 0.1 mg/kg/dose PO BID. Titrate up to 0.5 mg/kg/day or the adult maximum, whichever is less. Dosing for other ACE inhibitors in pediatrics is less well-established and may require specialist consultation. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary in patients with significantly impaired renal function. Specific recommendations vary by agent and degree of renal impairment. * **Hepatic Impairment:** Generally, dose adjustments are not required, but caution is advised. * **Volume Depletion/Hyponatremia:** Initiate at lower doses and titrate slowly. ## Contraindications * History of angioedema related to prior ACE inhibitor use * Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment * Pregnancy (especially second and third trimesters) * Known hypersensitivity to ACE inhibitors ## Adverse Effects * **Common:** Cough (dry, persistent), dizziness, hypotension, hyperkalemia, fatigue, headache. * **Serious:** Angioedema (potentially life-threatening), acute kidney injury, hyperkalemia, neutropenia/agranulocytosis (rare), hepatic dysfunction. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride) and Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction, particularly in elderly or volume-depleted patients. * **Lithium:** ACE inhibitors can increase lithium levels, potentially leading to toxicity. * **Diuretics:** Increased risk of hypotension, especially with loop diuretics. * **ARBs and Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use, particularly in high-risk populations. * **mTOR Inhibitors (e.g., everolimus, sirolimus):** Increased risk of angioedema. ## Monitoring * **Baseline:** Blood pressure, serum creatinine, electrolytes (especially potassium). * **During Therapy:** Blood pressure, serum creatinine, electrolytes (especially potassium) at regular intervals (e.g., 1-2 weeks after initiation or dose adjustment, then periodically). Assess for cough and signs/symptoms of angioedema. ## Clinical Pearls * Cough is a common side effect and often resolves upon discontinuation. If persistent and bothersome, consider switching to an ARB. * Angioedema is a medical emergency; discontinue immediately and manage airway. * Initiate at low doses in elderly, volume-depleted, or renally impaired patients. * Monitor potassium closely, especially in patients with renal impairment, diabetes, or those taking potassium supplements or potassium-sparing diuretics. * ACE inhibitors are renoprotective in patients with proteinuria, particularly diabetic nephropathy. Please verify current prescribing information for the most up-to-date details on dosing, contraindications, and interactions.