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# ACE Inhibitors
## 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)
* Myocardial Infarction (post-MI patients with LV dysfunction or overt HF)
* Diabetic Nephropathy (proteinuria)
## Adult Dosing
Dosing is highly individualized and depends on the specific agent, indication, and patient response. Titration is common.
* **Hypertension:** Initial doses vary by agent (e.g., lisinopril 10 mg PO once daily, enalapril 5 mg PO once or twice daily, ramipril 2.5 mg PO once daily). Maximum doses vary by agent (e.g., lisinopril up to 40 mg PO once daily, enalapril up to 40 mg PO once or twice daily, ramipril up to 10 mg PO once daily).
* **Heart Failure:** Initial doses are typically lower than for hypertension (e.g., lisinopril 5 mg PO once daily, enalapril 2.5 mg PO twice daily, ramipril 1.25 mg PO once daily). Target doses are higher and titrated based on tolerance and clinical response (e.g., lisinopril up to 40 mg PO once daily, enalapril up to 20 mg PO twice daily, ramipril up to 10 mg PO once daily).
* **Post-MI:** Generally started within 24 hours of MI in hemodynamically stable patients with evidence of LV dysfunction or HF. Dosing follows similar titration strategies as for heart failure.
* **Diabetic Nephropathy:** Dosing often mirrors that used for hypertension, titrated to achieve blood pressure goals and reduce proteinuria.
## Pediatric Dosing
Dosing in pediatric patients is less well-established and often requires individualized titration based on age, weight, and clinical response. Consult specific pediatric guidelines or literature.
* **Hypertension:** Captopril: 0.3-1 mg/kg/dose PO every 8-12 hours. Enalapril: 0.1-0.5 mg/kg/dose PO once daily or divided every 12 hours. Pediatric maximums apply and vary by agent.
## Dose Adjustments
* **Renal Impairment:** Dose reduction is often necessary, particularly in moderate to severe renal impairment. Specific recommendations vary by agent and creatinine clearance.
* **Hepatic Impairment:** Use with caution; dose adjustments may be needed for agents metabolized by the liver.
## Contraindications
* History of angioedema related to ACE inhibitor therapy.
* Concomitant use with aliskiren in patients with diabetes mellitus.
* Pregnancy (Category D in 2nd and 3rd trimesters).
## Adverse Effects
* **Common:** Cough (dry, persistent), dizziness, headache, fatigue, hyperkalemia.
* **Serious:** Angioedema (lips, face, tongue, throat, intestines), hypotension, renal insufficiency (especially in patients with bilateral renal artery stenosis), hyperkalemia, liver toxicity (rare), neutropenia/agranulocytosis (rare).
## Key Drug Interactions
* **Potassium-Sparing Diuretics/Potassium Supplements/ARBs/Aliskiren:** Increased risk of hyperkalemia.
* **NSAIDs/COX-2 Inhibitors:** May decrease antihypertensive effect and increase risk of renal dysfunction.
* **Diuretics (Thiazide, Loop):** Increased risk of hypotension, especially with initial doses or with sodium depletion.
* **Lithium:** ACE inhibitors can increase serum lithium levels, potentially leading to toxicity.
* **Mammalian target of rapamycin (mTOR) inhibitors (e.g., sirolimus, everolimus, temsirolimus):** Increased risk of angioedema.
## Monitoring
* **Blood Pressure:** Regularly monitor for hypotension and assess efficacy.
* **Renal Function:** Monitor serum creatinine and BUN, especially at initiation, dose changes, or in patients with risk factors.
* **Potassium:** Monitor serum potassium levels, particularly in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics or supplements.
* **Angioedema:** Educate patients on signs and symptoms and to report immediately.
## Clinical Pearls
* Cough is a common, dose-limiting side effect, usually reversible upon discontinuation.
* Angioedema is a rare but life-threatening adverse effect; patients should be counseled to seek immediate medical attention if symptoms occur.
* Initiate at low doses and titrate slowly, especially in elderly patients, those with volume depletion, or significant renal impairment.
* ACE inhibitors are generally considered renoprotective in patients with diabetes and proteinuria.
* Consider switching to an Angiotensin II Receptor Blocker (ARB) if cough is intolerable or angioedema occurs.
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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 clinical guidelines for complete details. Drug availability and dosing may vary by region.*
