Ace%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520inhibitors

# Angiotensin-Converting Enzyme (ACE) Inhibitors ## Overview ACE inhibitors are a class of medications that primarily 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, ultimately lowering blood pressure and reducing cardiac workload. ## Primary Indications * Hypertension * Heart Failure (reduced ejection fraction) * Post-Myocardial Infarction (to improve survival) * Diabetic Nephropathy (proteinuric kidney disease) ## Adult Dosing Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is common. * **Hypertension:** Initial doses vary by agent (e.g., lisinopril 10 mg once daily, enalapril 5 mg once or twice daily). Maximum doses vary by agent (e.g., lisinopril up to 40 mg once daily, enalapril up to 40 mg once daily). * **Heart Failure:** Often initiated at lower doses and titrated upwards (e.g., enalapril starting at 2.5 mg twice daily, titrating up to 10-20 mg twice daily). * **Post-MI:** Typically initiated after hemodynamic stabilization (e.g., captopril 6.25 mg three times daily, titrating to 50 mg three times daily). ## Pediatric Dosing Established pediatric dosing varies by agent and indication. Refer to specific drug monographs or pediatric formularies. * **Hypertension:** Doses are typically weight-based and depend on the agent. For example, enalapril: 0.07-0.1 mg/kg/dose orally every 8-24 hours. ## Dose Adjustments * **Renal Impairment:** Dose reduction is often necessary. Specific adjustments depend on the agent and degree of renal impairment (creatinine clearance). * **Hepatic Impairment:** Use with caution; dose adjustments may be needed for agents with significant hepatic metabolism (e.g., fosinopril). ## Contraindications * History of angioedema related to previous ACE inhibitor treatment * Concomitant use with aliskiren in patients with diabetes mellitus * Pregnancy (especially second and third trimesters) * Hypersensitivity to the specific ACE inhibitor ## Adverse Effects * **Cough:** Dry, persistent cough is common (up to 20%). * **Angioedema:** Rare but life-threatening swelling of the face, lips, tongue, and throat. * **Hyperkalemia:** Especially in patients with renal impairment or those taking potassium supplements or potassium-sparing diuretics. * **Hypotension:** Particularly with the first dose or in volume-depleted patients. * **Renal dysfunction:** Can worsen pre-existing renal failure or cause acute kidney injury, especially in susceptible individuals. * Dizziness, fatigue, headache, rash. ## Key Drug Interactions * **Potassium supplements, Salt substitutes, Potassium-sparing diuretics (e.g., spironolactone, amiloride), Trimethoprim:** Increased risk of hyperkalemia. * **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment. * **Diuretics:** Increased risk of symptomatic hypotension, especially with loop or thiazide diuretics. * **Lithium:** Increased serum lithium levels and risk of lithium toxicity. * **mTOR inhibitors (e.g., sirolimus, everolimus), DPP-4 inhibitors (e.g., saxagliptin, linagliptin):** Increased risk of angioedema. * **Sacubitril/Valsartan:** Increased risk of angioedema. ACE inhibitors should not be used within 36 hours of switching to or initiating sacubitril/valsartan. ## Monitoring * **Blood Pressure:** Regularly. * **Renal Function:** Serum creatinine and BUN, especially at initiation and dose changes. * **Potassium Levels:** Serum potassium, especially in patients with renal impairment, diabetes, or those on potassium-sparing agents. * **Signs of Angioedema:** Patient education is crucial. ## Clinical Pearls * First-dose hypotension is a concern, particularly in volume-depleted patients or those on diuretics. Consider initiating with a lower dose or withholding diuretics temporarily. * Cough is typically dose-dependent and may resolve with dose reduction or switching to an angiotensin II receptor blocker (ARB). * Discontinue ACE inhibitors immediately if angioedema occurs. * Consider switching to an ARB in patients experiencing persistent cough. * ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and local protocols for definitive guidance.*