Ace%25252525252525252525252525252525252525252525252525252520inhibitors

## 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) * 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. Typical starting doses are low and titrated upwards. * **Lisinopril:** Hypertension: 10 mg orally once daily, titrate to 20-40 mg daily. Heart failure: 5 mg orally once daily, titrate to 10-40 mg daily. * **Enalapril:** Hypertension: 5 mg orally once or twice daily, titrate to 10-40 mg daily in 1-2 divided doses. Heart failure: 2.5 mg orally twice daily, titrate to 10-20 mg daily in 2 divided doses. * **Ramipril:** Hypertension: 2.5 mg orally once daily, titrate to 10 mg daily. Heart failure: 2.5 mg orally twice daily, titrate to 5 mg twice daily. * **Benazepril:** Hypertension: 10 mg orally once daily, titrate to 20-40 mg daily. Heart failure: 5 mg orally once or twice daily, titrate to 10-20 mg daily in 2 divided doses. Maximum doses vary by agent and indication, consult specific drug monographs. ## Pediatric Dosing ACE inhibitors are generally not first-line agents in pediatric hypertension unless specific comorbidities exist. Dosing is based on weight and often initiated with lower doses than adults. * **Captopril:** Hypertension: 0.5 mg/kg/dose orally every 8-12 hours, titrate up to 1.5 mg/kg/dose every 6-12 hours (max 4.5 mg/kg/day or 150 mg/day). * **Enalaprilat (IV):** Hypertension: 0.01 mg/kg/dose IV every 6 hours. * **Enalapril (PO):** Hypertension: 0.07 mg/kg/dose orally once daily, titrate up to 0.21 mg/kg/dose once daily (max 40 mg/day). Consult pediatric-specific guidelines for detailed dosing recommendations. ## Dose Adjustments * **Renal Impairment:** Initiate with lower doses and titrate cautiously. In severe renal impairment, dose reductions may be necessary. Specific recommendations vary by agent. * **Hepatic Impairment:** Generally, no specific dose adjustment is required for hepatic impairment, but caution is advised. * **Volume Depletion/Hyponatremia:** Initiate with lower doses, often 50% of the usual starting dose. ## Contraindications * History of angioedema related to previous ACE inhibitor treatment. * Hereditary or idiopathic angioedema. * Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment. * Pregnancy (especially second and third trimesters - associated with fetal injury and death). ## Adverse Effects * **Most Common:** Dry, persistent cough, dizziness, hypotension, hyperkalemia, fatigue. * **Serious:** Angioedema (can be life-threatening), acute kidney injury, severe hypotension, neutropenia/agranulocytosis (rare). ## Key Drug Interactions * **Potassium-Sparing Diuretics (e.g., Spironolactone, Amiloride) & Potassium Supplements:** Increased risk of hyperkalemia. * **NSAIDs & COX-2 Inhibitors:** May attenuate antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients. * **Lithium:** ACE inhibitors can decrease lithium clearance, increasing lithium toxicity risk. Monitor lithium levels closely. * **ARBs & Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal impairment. Avoid concurrent use. * **Diuretics:** Additive hypotensive effect, increased risk of hypovolemia and hypotension. ## Monitoring * **Blood Pressure:** Regularly monitor for hypotension, especially after initiation or dose increases. * **Renal Function (Serum Creatinine, BUN):** Monitor periodically, especially in patients with pre-existing renal disease, heart failure, or dehydration. * **Serum Potassium:** Monitor for hyperkalemia, especially in patients with renal impairment, diabetes, or those taking potassium supplements/sparing diuretics. * **Angioedema:** Educate patients on signs and symptoms and to seek immediate medical attention if they occur. ## Clinical Pearls * ACE inhibitors are highly effective for patients with diabetes, particularly those with proteinuria, as they can slow the progression of diabetic nephropathy. * The dry cough is a dose-limiting side effect for some patients and may necessitate switching to an Angiotensin II Receptor Blocker (ARB). * Initiation in hypovolemic patients or those on diuretics requires caution and often a lower starting dose. * Angioedema is a rare but serious adverse effect that can occur at any time during treatment and requires immediate discontinuation of the ACE inhibitor and all other potentially causative agents. *** **Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines before making any clinical decisions. Individual patient factors should always be considered.