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# ACE Inhibitors
## Overview
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications primarily used to manage cardiovascular diseases. 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 with reduced ejection fraction (HFrEF)
* Post-myocardial infarction (MI) in patients with evidence of LV dysfunction or heart failure
* Diabetic nephropathy (particularly in type 1 diabetes with proteinuria)
* Chronic kidney disease (CKD) with proteinuria
## Adult Dosing
Dosing varies significantly by agent, indication, and patient response. Titration is common.
* **Hypertension:**
* Benazepril: 10-40 mg once daily
* Captopril: 25-150 mg divided twice daily (max 450 mg/day)
* Enalapril: 5-40 mg once or twice daily
* Fosinopril: 10-40 mg once daily
* Lisinopril: 10-40 mg once daily (max 80 mg/day)
* Moexipril: 7.5-30 mg once daily
* Perindopril: 2.5-10 mg once daily
* Quinapril: 5-40 mg divided twice daily
* Ramipril: 2.5-10 mg once daily
* Trandolapril: 1-4 mg once daily
* **Heart Failure (HFrEF):**
* Captopril: Start 6.25 mg TID, titrate up to 50 mg TID
* Enalapril: Start 2.5 mg BID, titrate up to 10-20 mg BID
* Lisinopril: Start 5 mg QD, titrate up to 10-40 mg QD
* Ramipril: Start 1.25-2.5 mg QD, titrate up to 10 mg QD
* **Post-MI:**
* Captopril: Start 6.25 mg TID, titrate to 50 mg TID
* Enalapril: Start 2.5 mg BID, titrate to 5 mg BID, then to 10 mg BID
* Lisinopril: Start 5 mg QD, titrate to 10 mg QD, then to 20 mg QD
* **Diabetic Nephropathy/CKD with Proteinuria:** Dosing similar to hypertension, aiming to reduce proteinuria. Target doses are often higher than those used solely for blood pressure control.
## Pediatric Dosing
* **Hypertension:** Dosing varies by age and weight. Consult specific pediatric guidelines.
* Enalapril: 0.07-0.1 mg/kg/dose PO once daily; may increase to BID. Max dose: 0.5 mg/kg/day.
* Captopril: 0.3 mg/kg/dose PO TID. Max dose: 4.5 mg/kg/day.
* Lisinopril: 0.07-0.2 mg/kg/dose PO once daily. Max dose: 20 mg/day.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary, especially for renally excreted ACE inhibitors (e.g., captopril, enalapril, lisinopril). Monitor serum creatinine and potassium.
* **Hepatic Impairment:** May require dose reduction for prodrugs (e.g., enalapril, ramipril).
## Contraindications
* History of angioedema related to ACE inhibitor therapy
* Concomitant use with aliskiren in patients with diabetes mellitus or moderate to severe renal impairment
* Pregnancy (especially second and third trimesters)
* Known hypersensitivity to ACE inhibitors
## Adverse Effects
* **Common:** Dry cough (dose-related), dizziness, fatigue, headache, hyperkalemia, hypotension.
* **Less Common/Serious:** Angioedema (potentially life-threatening, can occur at any time), renal impairment/failure (especially in susceptible individuals), neutropenia/agranulocytosis (rare), hepatic dysfunction, rash, taste disturbances.
## Key Drug Interactions
* **Potassium-sparing diuretics, potassium supplements, salt substitutes:** Increased risk of hyperkalemia.
* **Aliskiren:** Increased risk of hyperkalemia, hypotension, and renal dysfunction; avoid concomitant use in patients with diabetes or renal impairment.
* **Angiotensin II Receptor Blockers (ARBs):** Increased risk of hyperkalemia, hypotension, and renal dysfunction.
* **NSAIDs/COX-2 inhibitors:** May reduce antihypertensive effect and increase risk of renal dysfunction.
* **Diuretics (thiazide and loop):** Increased risk of hypotension, especially with first-dose effect.
* **Mammalian Target of Rapamycin (mTOR) inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema.
* **Racecadotril:** 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 (before and after initiation/titration)
* Serum electrolytes (especially potassium)
* Renal function (serum creatinine, BUN)
* Signs and symptoms of angioedema
* Signs of infection (if neutropenia is suspected)
## Clinical Pearls
* The characteristic dry cough is thought to be due to increased bradykinin levels and is generally reversible upon discontinuation.
* Angioedema is a medical emergency. Patients should be advised to stop the medication immediately and seek emergency care if swelling of the face, lips, tongue, or throat occurs.
* First-dose hypotension is more likely in patients who are volume-depleted or on concurrent diuretic therapy.
* ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria.
* Prodrugs (e.g., enalapril, ramipril) require hepatic activation and may have slower onset of action compared to direct-acting ACE inhibitors (e.g., captopril, lisinopril).
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*This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for specific patient care decisions.*
