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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used for cardiovascular conditions. They work by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation, reduced aldosterone secretion, and decreased sympathetic nervous system activity.
## Primary Indications
* Hypertension
* Heart failure (systolic dysfunction)
* Post-myocardial infarction (to improve survival)
* Diabetic nephropathy (proteinuria reduction)
* Chronic kidney disease (proteinuria reduction)
## Adult Dosing
Dosing varies significantly by agent, indication, and patient response. Titration is common.
* **Hypertension:** Initial doses are typically low and titrated upwards every 2-4 weeks.
* Benazepril: 10 mg orally once daily, titrate up to 40 mg/day.
* Captopril: 25 mg orally twice daily, titrate up to 50 mg three times daily.
* Enalapril: 10 mg orally once daily, titrate up to 40 mg/day.
* Lisinopril: 10 mg orally once daily, titrate up to 40 mg/day.
* Ramipril: 2.5 mg orally once daily, titrate up to 10 mg/day.
* *Max doses vary by agent and should be guided by clinical response and tolerability.*
* **Heart Failure:** Typically initiated at a low dose and titrated to target doses or maximally tolerated doses.
* Enalapril: 2.5 mg orally twice daily, titrate up to 10 mg twice daily.
* Lisinopril: 5 mg orally once daily, titrate up to 20 mg once daily.
* Ramipril: 1.25 mg orally once daily, titrate up to 5 mg twice daily.
* **Post-MI:** Initiate within 24 hours in hemodynamically stable patients.
* Captopril: 6.25 mg orally three times daily, increase to 12.5 mg three times daily, then 25 mg three times daily.
* Enalapril: 2.5 mg orally twice daily, increase to 5 mg twice daily, then 10 mg twice daily.
* **Diabetic/Chronic Kidney Disease:** Dosing is individualized.
## Pediatric Dosing
Dosing in pediatric patients is weight-based and should be determined by a pediatric specialist.
* **Hypertension:**
* Benazepril: 0.1-0.3 mg/kg/day orally divided once or twice daily (max 0.6 mg/kg/day or 40 mg/day).
* Enalapril: 0.07-0.1 mg/kg/dose orally every 12-24 hours (max 0.57 mg/kg/day or 40 mg/day).
* Lisinopril: 0.07-0.2 mg/kg/day orally once daily (max 20 mg/day).
* *Specific recommendations and maximums vary by agent and age group.*
## Dose Adjustments
* **Renal Impairment:** Reduce initial dose and titrate cautiously. Captopril and lisinopril require more significant dose adjustments in severe renal impairment.
* **Hepatic Impairment:** Generally no dose adjustment needed, but caution is advised.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes.
* Concomitant use with sacubitril/valsartan (within 36 hours of the last dose of sacubitril/valsartan).
* Pregnancy (especially second and third trimesters).
* Hypersensitivity to the specific ACE inhibitor.
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia, hypotension, rash.
* **Serious:** Angioedema (including laryngeal), acute kidney injury, severe hypotension, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, salt substitutes:** Increased risk of hyperkalemia.
* **Aliskiren, ARBs:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid in combination with aliskiren in diabetics.
* **NSAIDs:** May reduce antihypertensive effect and increase risk of renal dysfunction.
* **Lithium:** Reduced lithium clearance, increased risk of lithium toxicity.
* **Sacubitril/Valsartan:** Increased risk of angioedema. Avoid concomitant use.
* **Diuretics:** Additive hypotensive effect.
## Monitoring
* Blood pressure (before and after initiation/titration).
* Serum potassium.
* Renal function (serum creatinine, BUN).
* Monitor for signs and symptoms of angioedema.
* Complete blood count (especially in those with risk factors for neutropenia).
## Clinical Pearls
* The characteristic dry cough is thought to be due to increased bradykinin levels. Discontinuation of the ACE inhibitor usually resolves the cough.
* Hypotension can occur, especially in volume-depleted patients, those on diuretics, or with heart failure. Consider initiating at lower doses and titrating slowly.
* Angioedema is a rare but serious adverse effect that can occur at any time during treatment and is a contraindication to future use.
* Monitor electrolytes and renal function closely, especially in patients with pre-existing renal disease, heart failure, or those taking potassium-sparing agents.
* Do not use in pregnancy due to risk of fetal harm.
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*This information is intended for healthcare professionals and does not substitute for comprehensive drug reference materials. Always consult current prescribing information for specific product details and guidelines.*
