Epinephrine is the first-line treatment for severe, histamine-mediated angioedema, especially when there is airway swelling, difficulty breathing, or anaphylaxis. It works by constricting blood vessels, relaxing airway muscles, and blocking further histamine release, rapidly reducing swelling and improving breathing. It is usually given as an intramuscular injection in the thigh (e.g., EpiPen), but can also be administered intravenously in the emergency setting under close monitoring. However, epinephrine is not effective for bradykinin-mediated angioedema (such as hereditary or ACE inhibitor–induced types).