A patient with a documented penicillin allergy is prescribed cephalexin and develops shortness of breath 30 minutes later. Which mediator is primarily responsible?

Correct answer: B. Histamine

• A. EPINEPHRINE is the TREATMENT, not the mediator causing the reaction. This is the classic distractor — read the question carefully: it asks what molecule is INVOLVED in producing the symptoms.
• B. CORRECT. This is a TYPE I, IgE-mediated hypersensitivity reaction resulting from cross-reactivity between penicillins and cephalosporins (they share a beta-lactam ring; cross-reactivity with first-generation cephalosporins such as cephalexin is real, though lower than historically taught — roughly 1–2%). IgE bound to mast cells and basophils triggers degranulation, releasing preformed HISTAMINE, which causes bronchoconstriction, vasodilation, increased vascular permeability, urticaria, and angioedema.
• C. Serotonin is a mediator in rodent mast cells but plays little role in human anaphylaxis.
• D. Bradykinin mediates ACE-inhibitor angioedema — a non-allergic mechanism that does NOT respond to epinephrine or antihistamines the way anaphylaxis does.

Note: That is wrong — epinephrine is the antidote. Histamine is the mediator.