Diphenhydramine (Benadryl) is a first generation antihistamine which blocks H1 histamine receptors. Unlike many second generation antihistamines, first generation medications like diphenhydramine cross the blood-brain barrier and inhibit histamine’s important role in sleep and wakefulness. Couple this with diphenhydramine’s anticholinergic effects in the central nervous system, and one can see the sedating and deliriogenic potential of this medication (especially in the elderly) which can lead to cognitive impairment. For this reason, I find it worrisome when elderly patients are admitted with Benadryl as a “home sleep aid.”

As an intensivist and anesthesiologist, I administer diphenhydramine for seasonal allergies, mild allergic reaction to medications/transfusions, generalized pruritus that I feel is attributed to histamine release (ie, NOT itchiness related to epidurals/spinals), and as a part of treating suspected anaphylaxis.

In general, if my patients are tolerating oral medications, I’d rather use second generation antihistamines like loratidine, fexofenadine, and cetirizine due to more favorable side effect profiles.

Drop me a comment below with questions! 🙂

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