Mechanism explains both benefits (itch relief) and side effects (sleepiness, dry mouth).
Diphenhydramine is a first‑generation antihistamine that acts as an inverse agonist at H1 receptors, reducing histamine‑mediated symptoms like itching and swelling. It crosses the blood–brain barrier and has anticholinergic properties, leading to sedation and typical anticholinergic effects.
Diphenhydramine blocks the body’s histamine signals that cause itch and hives, but it can make kids sleepy.
Think of it like this: It’s like turning off the ‘itch switch’ while dimming the brain’s alertness lights.
A small number of children experience paradoxical excitation. Stop and call your provider.
Yes—non‑sedating antihistamines are better for school days.
GPCR - inverse_agonist
Reduces allergic itch and swelling
GPCR - antagonist
Dry mouth, constipation, urinary retention, blurry vision
H1 inverse agonism reduces histamine‑mediated itching and swelling; anticholinergic action contributes to sedation
Bioavailability
High
Time to Peak
~2 h
Food Effect
Route
Oral
Hepatic (CYP‑mediated)
Pediatric: Developing enzymes may alter kinetics in young children
Half-life
~4–8 h
Primary Route
Renal (metabolites)
Dosing Implication
q6–8h dosing typical
Near adult absorption
Developing hepatic enzymes
High CNS penetration
Greater sensitivity to sedation and anticholinergic effects
First test dose in evening to gauge sedation vs excitation