hydroxyzine
Brand: Atarax, Vistaril
Beers Criteria Prototype: diphenhydramine
Drug Class: antihistamine / anxiolytic / antiemetic
Drug Family: antihistamine
Subclass: first-generation H1 receptor antagonist with CNS effects
Organ Systems: cns
Mechanism of Action
Centrally active first-generation H1 antihistamine with anxiolytic, antipruritic, antiemetic, and sedative properties. CNS histamine H1 blockade produces sedation; anxiolytic effect is incompletely understood but may involve mild serotonin antagonism. Also blocks muscarinic receptors (anticholinergic effects) and alpha-1 adrenergic receptors.
H1 histamine receptors (CNS and peripheral)muscarinic receptors (anticholinergic)alpha-1 adrenergic receptors
Indications
- anxiety and tension (short-term)
- pruritus (allergic and non-allergic)
- nausea and vomiting (preoperative, pregnancy)
- sedation (preoperative, procedural)
Contraindications
- early pregnancy (Vistaril — risk of fetal abnormalities)
- prolonged QT interval
Adverse Effects
Common
- sedation
- dry mouth
- constipation
- urinary retention
- blurred vision
Serious
- QT prolongation (rare)
- anticholinergic toxidrome (overdose)
- paradoxical excitation (rare in children)
Pharmacokinetics (ADME)
| Absorption | oral or IM; well absorbed |
| Distribution | crosses BBB extensively; high Vd |
| Metabolism | hepatic; active metabolite cetirizine |
| Excretion | renal |
| Half-life | 20–25 hours (increased in elderly) |
| Onset | 15–30 minutes (IM) |
| Peak | 2 hours |
| Duration | 4–6 hours |
| Protein Binding | 93% |
| Vd | 16–20 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CNS depressants | additive sedation | moderate |
| anticholinergic drugs | additive anticholinergic effects | moderate |
| QT-prolonging drugs | additive QT prolongation risk | moderate |
Nursing Considerations
- IM injection must be given into a large muscle (gluteal or lateral thigh); NEVER administer IV or subcutaneous — tissue necrosis, thrombosis, and inadvertent intra-arterial injection can cause severe harm.
- Advise patients about sedation; avoid driving.
- Monitor for anticholinergic effects in elderly; Beers Criteria — avoid in older adults.
- Safe alternative to benzodiazepines for acute anxiety in patients with substance use disorders — no abuse potential.
Clinical Pearls
- Hydroxyzine's daughter metabolite cetirizine (Zyrtec) is a widely used second-generation antihistamine with much less CNS penetration — cetirizine lacks the anxiolytic and sedative effects of hydroxyzine because it crosses the BBB poorly.
- Hydroxyzine is increasingly popular as an acute anxiety treatment in emergency settings for patients with opioid or benzodiazepine use disorder, as it provides sedation and anxiolysis without dependence or abuse potential.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.