Diphenhydramine (Benadryl) is the most common first-generation antihistamine found in OTC sleep aids, whether used alone or in combination with pain relievers, including acetaminophen (eg, Tylenol PM), ibuprofen (eg, Advil PM), and aspirin.
Currently the only FDA-approved histamine antagonist medications block the effects of histamine at H1 or H2 receptor sites.
Antihistamines are classified into two groups – the first-generation (“sedating”) and second-generation (“non-sedating”).
Sedating antihistamines cause sedation as they are highly lipid soluble and readily cross the blood brain barrier.
Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil.
Once released, the histamine can react with local or widespread tissues through histamine receptors.
First-generation antihistamines are widely available without a prescription and commonly used to treat allergic symptoms, including rhinitis, conjunctivitis, pruritus, eczema, urticaria, and anaphylactic reactions.