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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications 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 (proteinuria reduction)
## Adult Dosing
Dosing is highly individualized and depends on the specific ACE inhibitor, indication, and patient response. Titration is typically done every 1-4 weeks.
* **Hypertension:**
* Benazepril: Initial 10 mg once daily, usual 20-40 mg once daily. Max 80 mg/day.
* Captopril: Initial 12.5-25 mg BID, usual 50 mg TID. Max 150 mg TID.
* Enalapril: Initial 5 mg once daily, usual 10-40 mg once daily. Max 40 mg/day.
* Fosinopril: Initial 10 mg once daily, usual 20-40 mg once daily. Max 80 mg/day.
* Lisinopril: Initial 10 mg once daily, usual 20-40 mg once daily. Max 80 mg/day.
* Moexipril: Initial 7.5 mg once daily, usual 15-30 mg once daily. Max 30 mg/day.
* Perindopril: Initial 2.5-5 mg once daily, usual 5-10 mg once daily. Max 10 mg/day.
* Quinapril: Initial 10 mg once daily, usual 20-40 mg BID. Max 80 mg/day.
* Ramipril: Initial 2.5 mg once daily, usual 5-10 mg once daily. Max 10 mg/day.
* Trandolapril: Initial 0.5-1 mg once daily, usual 1-4 mg once daily. Max 4 mg/day.
* **Heart Failure:** Dosing is generally higher than for hypertension and requires careful titration. Refer to specific drug monographs for detailed titration schedules.
* **Post-MI:** Typically initiated within 24 hours in hemodynamically stable patients. Refer to specific drug monographs.
* **Diabetic Nephropathy:** Refer to specific drug monographs.
## Pediatric Dosing
Dosing in children is less established and requires careful consideration.
* **Hypertension:**
* Enalapril: 0.07-0.1 mg/kg/dose orally every 12-24 hours. Max 0.61 mg/kg/day or 40 mg/day.
* Lisinopril: 0.07-0.2 mg/kg/dose orally every 24 hours. Max 20 mg/day.
* Captopril: 0.3-0.5 mg/kg/dose orally every 8-12 hours. Max 6 mg/kg/day or 150 mg/day.
## Dose Adjustments
* **Renal Impairment:** Reduce dose and/or increase dosing interval. Captopril and fosinopril may require less adjustment than others due to different elimination pathways.
* **Hepatic Impairment:** Use with caution; reduced clearance may occur.
## Contraindications
* History of angioedema related to previous ACE inhibitor treatment.
* Hereditary or idiopathic angioedema.
* Concomitant use with aliskiren in patients with diabetes or renal impairment.
* Second and third trimesters of pregnancy.
## Adverse Effects
* **Common:** Dry cough, dizziness, hyperkalemia, fatigue, hypotension.
* **Serious:** Angioedema (face, lips, tongue, throat, intestines), acute kidney injury, hyperkalemia, neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, spironolactone, eplerenone, trimethoprim, salt substitutes:** Increased risk of hyperkalemia.
* **NSAIDs, COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal impairment, especially in elderly or volume-depleted patients.
* **Diuretics (especially loop and thiazide):** Increased risk of hypotension, particularly upon initiation.
* **Lithium:** ACE inhibitors can decrease lithium clearance, increasing serum lithium levels.
* **mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema.
* **ARBs, Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction. Avoid concomitant use in high-risk patients.
## Monitoring
* **Blood Pressure:** Regularly monitor before and after dose initiation or adjustment.
* **Renal Function:** Serum creatinine and BUN, especially in patients with pre-existing renal disease or those at risk.
* **Potassium:** Serum potassium levels, particularly in patients with renal impairment, diabetes, or on potassium-sparing agents.
* **Angioedema:** Educate patients to report any signs or symptoms immediately.
## Clinical Pearls
* The characteristic dry cough is thought to be due to bradykinin accumulation and is usually reversible upon discontinuation.
* ACE inhibitors can be renoprotective in patients with diabetes and proteinuria.
* First-dose hypotension can occur, especially in patients who are volume-depleted or on diuretics. Consider withholding diuretics for 2-3 days before starting an ACE inhibitor.
* Angioedema can occur at any time during therapy and is a medical emergency. Discontinue ACE inhibitor immediately if angioedema is suspected.
* Due to the potential for teratogenicity, ACE inhibitors are contraindicated in pregnancy.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details before making any treatment decisions.*
