Diphenhydramine
Benadryl
First-generation H1 receptor antagonist
Competitive H1 antagonist with significant anticholinergic + sedating activity from CNS penetration. Crosses BBB freely.
Indications
- •Allergic / anaphylactic reactions (with epinephrine + steroid)
- •Pre-treatment for contrast-allergy patients
- •PONV adjunct
- •Acute dystonic reaction reversal
- •Pruritus (drug-induced, neuraxial-opioid)
Dosing
| 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 | — |
Pharmacokinetics
Onset 15 min IV. Peak 1 h. Duration 4–6 h. Hepatic metabolism.
Hemodynamic effects
Mild hypotension on rapid IV push (vasodilation).
Respiratory effects
Mild drying of secretions; can thicken bronchial secretions in asthmatics (relative caution).
Side effects
- !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
Contraindications
- ×Narrow-angle glaucoma
- ×Severe BPH / urinary obstruction
- ×Neonates (paradoxical CNS excitation)
- ×Concurrent MAOIs
Clinical pearls
- ★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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Other drugs in Antihistamines
- Famotidine
Reversible competitive antagonist at parietal cell H2 receptors → reduces basal + stimulated gastric acid secretion. Raises gastric pH within 30 min.
- Cetirizine
Selective peripheral H1 antagonist. Carboxylic acid structure → poor BBB penetration → minimal sedation compared with first-generation antihistamines like diphenhydramine.
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