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# ACE Inhibitors
## Overview
ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) are a class of medications primarily used to treat cardiovascular conditions by blocking 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 (with reduced ejection fraction)
* Post-Myocardial Infarction (to improve survival and reduce reinfarction)
* Diabetic Nephropathy (to slow progression)
## Adult Dosing
Dosing varies significantly by specific ACE inhibitor, indication, and patient factors. Titration is typically guided by blood pressure response and tolerability.
* **Hypertension:** Initial doses are generally low and titrated upwards every 2-4 weeks.
* Benazepril: 10-40 mg once daily
* Captopril: 25 mg twice daily, titrate up to 50 mg three times daily
* Enalapril: 5-10 mg once daily, titrate up to 10-40 mg once or twice daily
* Fosinopril: 10-40 mg once daily
* Lisinopril: 10 mg once daily, titrate up to 20-40 mg once daily
* Moexipril: 7.5-15 mg once daily, titrate up to 30 mg once daily
* Perindopril: 5-10 mg once daily, titrate up to 10-20 mg once daily
* Ramipril: 2.5-5 mg once daily, titrate up to 10 mg once daily
* Trandolapril: 1-4 mg once daily
* Quinapril: 10-20 mg once or twice daily, titrate up to 40 mg twice daily
* **Heart Failure:** Dosing often starts lower than for hypertension and is titrated cautiously.
* Captopril: 6.25 mg three times daily, titrate up to 50 mg three times daily
* Enalapril: 2.5 mg twice daily, titrate up to 10-20 mg twice daily
* Lisinopril: 5 mg once daily, titrate up to 10-40 mg once daily
* Ramipril: 2.5 mg twice daily, titrate up to 5 mg twice daily (often preferred in certain guidelines)
* **Post-MI:** Initiated within 24 hours in hemodynamically stable patients.
* Captopril: 6.25 mg three times daily, then titrate upwards.
* Enalapril: 2.5 mg twice daily, then titrate upwards.
* Lisinopril: 5 mg once daily, then titrate upwards.
## Pediatric Dosing
Dosing in children is based on body surface area or weight and varies by agent. Pediatric dosing is often not well-established for all ACE inhibitors, and use should be guided by expert consultation and careful monitoring.
* **Hypertension:**
* Enalapril: 0.07 mg/kg/day (maximum 40 mg/day), divided once or twice daily.
* Lisinopril: 0.07 mg/kg/day (maximum 40 mg/day), once daily.
* Captopril: 0.3 mg/kg/dose (maximum 150 mg/day), divided three times daily.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is generally required for patients with impaired renal function (creatinine clearance < 30 mL/min). Specific guidelines vary by agent. Captopril and fosinopril may require less adjustment than others.
* **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 of aliskiren in patients with diabetes or renal impairment.
* Pregnancy (Category D in 2nd and 3rd trimesters).
## Adverse Effects
* **Most Common:** Cough (dry, persistent), hyperkalemia, dizziness, fatigue, hypotension.
* **Less Common but Serious:** Angioedema (potentially life-threatening), acute kidney injury, rash, dysgeusia, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-Sparing Diuretics/Potassium Supplements/ARBs/Aliskiren:** Increased risk of hyperkalemia.
* **NSAIDs/COX-2 Inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in volume-depleted patients.
* **Diuretics (Thiazide/Loop):** Increased risk of hypotension, especially upon initiation.
* **Lithium:** ACE inhibitors can decrease lithium clearance, leading to lithium toxicity.
## Monitoring
* **Renal Function (BUN, Creatinine):** Baseline and periodically, especially with dose changes or in patients with risk factors.
* **Serum Potassium:** Baseline and periodically.
* **Blood Pressure:** Regularly, especially after initiation and dose titration.
* **Signs/Symptoms of Angioedema:** Educate patients to report immediately.
## Clinical Pearls
* Cough is a common side effect, often necessitating discontinuation and switch to an ARB.
* Angioedema can occur at any time, even after prolonged use.
* Initiate at low doses and titrate slowly, especially in elderly patients, volume-depleted patients, or those with renal impairment.
* ACE inhibitors are renoprotective in patients with diabetes and proteinuria.
* May cause a false-positive urine protein test.
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*This information is intended for healthcare professionals and is not a substitute for clinical judgment. Always refer to the most current prescribing information and relevant guidelines for complete details. Dosing may vary based on specific patient factors and local protocols.*
