Diphenhydramine

Benadryl

First-generation H1 receptor antagonist

Competitive H1 antagonist with significant anticholinergic + sedating activity from CNS penetration. Crosses BBB freely.

Indications

Context	Adult	Pediatric
Allergic reaction	25–50 mg IV/IM/PO q6 h	1 mg/kg (max 50 mg) IV/IM
Dystonic reaction	50 mg IV slow push	—
Anaphylaxis adjunct (NOT first-line)	50 mg IV after epinephrine	—

Onset 15 min IV. Peak 1 h. Duration 4–6 h. Hepatic metabolism.

Mild hypotension on rapid IV push (vasodilation).

Mild drying of secretions; can thicken bronchial secretions in asthmatics (relative caution).

!Sedation — major reason it's avoided in elderly + ambulatory anesthesia
!Anticholinergic load (dry mouth, urinary retention, constipation, delirium in elderly)
!Paradoxical excitation in children
!QT prolongation at high doses
!Tachycardia

★ANAPHYLAXIS: NEVER first-line. Epinephrine first, fluids second, steroid + H1/H2 are adjuncts that don't replace epi.
★ELDERLY: avoid. Beers Criteria explicitly lists diphenhydramine — major delirium driver postoperatively.
★DYSTONIC REACTION: 50 mg IV breaks an acute dystonia (e.g., from metoclopramide) within 5 min — diagnostic and therapeutic.
★AMBULATORY: post-discharge driving impairment well-documented at 50 mg PO. Counsel patients.

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