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# ACE Inhibitors ## Overview Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used for managing cardiovascular and renal conditions. They work by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure and cardiac workload. ## Primary Indications * Hypertension * Heart Failure (systolic dysfunction) * Myocardial Infarction (post-MI, in select patients) * Diabetic Nephropathy (in patients with proteinuria) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is essential. * **Hypertension:** Typical starting doses include enalapril 5 mg once or twice daily, lisinopril 10 mg once daily, ramipril 2.5 mg once daily. Maximum doses vary by agent, e.g., enalapril up to 40 mg/day, lisinopril up to 40 mg/day, ramipril up to 10 mg/day. * **Heart Failure:** Typical starting doses include enalapril 2.5 mg to 5 mg twice daily, lisinopril 5 mg once daily, ramipril 1.25 mg to 2.5 mg once daily. Doses are titrated upwards as tolerated. Max doses for HF are often higher than for hypertension, e.g., enalapril up to 40 mg/day divided bid, lisinopril up to 35 mg/day, ramipril up to 10 mg/day. * **Post-MI:** Generally initiated within 24 hours if no contraindications. Dosing aligns with hypertension or heart failure indications based on hemodynamic stability and symptoms. * **Diabetic Nephropathy:** Dosing is similar to hypertension, aiming for blood pressure control and proteinuria reduction. ## Pediatric Dosing ACE inhibitors are used in pediatric patients, but dosing is often weight-based and may require specialist consultation. * **Hypertension:** Doses vary significantly by agent. For example, enalapril: 0.07 to 0.1 mg/kg/dose given once or twice daily. Maximum doses are typically weight-based or capped at adult maximums. Specific protocols should be consulted. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary in patients with renal insufficiency (creatinine clearance < 30 mL/min). Specific adjustments depend on the individual ACE inhibitor and degree of renal impairment. * **Hepatic Impairment:** Generally, no specific dose adjustment is needed, but caution is advised. * **Volume Depletion/Hyponatremia:** Lower initial doses and slower titration are recommended. ## Contraindications * History of angioedema related to prior ACE inhibitor treatment * Hereditary or idiopathic angioedema * Concomitant use with aliskiren in patients with diabetes mellitus * Pregnancy (Category D in 2nd and 3rd trimesters, Category C in 1st trimester) - *risk of fetal injury or death* ## Adverse Effects * **Most Common:** Dry, persistent cough; dizziness; hyperkalemia; hypotension. * **Serious:** Angioedema (potentially life-threatening); acute kidney injury (especially in patients with bilateral renal artery stenosis); hyperkalemia; neutropenia/agranulocytosis (rare); elevated liver enzymes. ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., spironolactone, amiloride), Potassium Supplements, ARBs, Aliskiren:** Increased risk of hyperkalemia. * **NSAIDs:** May reduce antihypertensive effect and increase risk of renal impairment, particularly in the elderly or volume-depleted. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing the risk of lithium toxicity. * **Diuretics (especially loop or thiazide):** Increased risk of hypotension, particularly upon initiation. Consider lower doses of ACE inhibitor or diuretic. ## Monitoring * **Baseline:** Serum creatinine, electrolytes (especially potassium), blood pressure. * **During Therapy:** * **Renal Function:** Monitor serum creatinine and BUN within 1-2 weeks of initiation or dose increase, and periodically thereafter. A rise in creatinine up to 30% is often acceptable if stable. * **Electrolytes:** Monitor potassium, especially in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics. * **Blood Pressure:** Regular monitoring to assess efficacy and identify hypotension. * **Signs/Symptoms:** Monitor for cough, angioedema, dizziness. ## Clinical Pearls * Initiate at low doses and titrate slowly, especially in elderly patients, those with heart failure, or renal impairment. * The dry cough is generally reversible upon discontinuation. Consider switching to an Angiotensin II Receptor Blocker (ARB) if cough is intolerable. * Contraindicated in pregnancy due to risk of fetal harm. * Caution is advised in patients with bilateral renal artery stenosis due to the risk of acute kidney injury. * Angioedema is a medical emergency and requires immediate discontinuation of the ACE inhibitor. *** **Disclaimer:** This information is intended for healthcare professionals and does not replace professional medical judgment. Always verify current prescribing information, guidelines, and institutional protocols before making clinical decisions.