Is hydroxyzine (an antihistamine) an anticholinergic?

Hydroxyzine is a First-Generation Antihistamine with Anticholinergic Properties

Yes, hydroxyzine is an antihistamine with significant anticholinergic effects. 1 The anticholinergic properties of hydroxyzine contribute to its side effect profile and are an important consideration when prescribing this medication, especially for certain patient populations.

Classification and Pharmacological Properties

Hydroxyzine belongs to the first-generation antihistamine class, which is characterized by:

• H1-receptor antagonism
• Significant anticholinergic activity
• Blood-brain barrier penetration leading to CNS effects
• Sedative properties

Anticholinergic Effects of Hydroxyzine

The anticholinergic effects of hydroxyzine include:

• Dry mouth and eyes
• Constipation
• Urinary retention (inhibition of micturition)
• Increased risk for provoking narrow-angle glaucoma 1
• Potential cognitive impairment, especially in older adults

Clinical Implications

Patient Populations Requiring Special Consideration

1. Older Adults:

   • More sensitive to psychomotor impairment
   • Increased risk for falls and associated complications (fractures, subdural hematomas)
   • More susceptible to adverse anticholinergic effects 1
   • Should be used with extra caution in those with comorbidities like increased intraocular pressure, benign prostatic hypertrophy, or cognitive impairment

2. Patients with Dementia:

   • Anticholinergic medications like hydroxyzine are frequently used in older adults with dementia despite potential risks 2
   • May worsen cognitive function

3. Patients with Hepatic Impairment:

   • Should be avoided in severe liver disease due to sedating effects 1

4. Patients with Renal Impairment:

   • Dose should be halved in renal impairment 1

5. Pregnant Women:

   • Hydroxyzine is specifically contraindicated during early stages of pregnancy according to UK manufacturer's guidelines 1

Therapeutic Considerations

When considering hydroxyzine for treatment:

• For Allergic Rhinitis: Second-generation antihistamines are generally preferred over first-generation antihistamines like hydroxyzine due to their better safety profile and reduced anticholinergic effects 1

• For Urticaria:

  • May be used as a sedating antihistamine at night (10-50 mg) in combination with a non-sedating antihistamine during the day 1
  • However, second-generation agents are preferred due to reduced anticholinergic burden 3

• For Anxiety:

  • While hydroxyzine has been used for generalized anxiety disorder, its anticholinergic and sedative effects may limit its utility 4

Comparison with Other Antihistamines

• First-generation antihistamines (including hydroxyzine, diphenhydramine, clemastine):

  • All have significant anticholinergic properties
  • Associated with sedation and performance impairment

• Second-generation antihistamines (cetirizine, loratadine, fexofenadine, etc.):

  • Have less or no anticholinergic effects 1
  • Generally preferred for most indications due to better safety profile
  • Cetirizine (the active metabolite of hydroxyzine) has reduced but still present sedative properties compared to hydroxyzine 1

Risk Mitigation

To minimize risks associated with hydroxyzine's anticholinergic properties:

1. Consider alternative non-anticholinergic medications when possible
2. Use the lowest effective dose
3. Monitor for anticholinergic side effects
4. Avoid combination with other medications having anticholinergic properties
5. Consider topical rather than systemic administration when appropriate 5
6. Educate patients about potential side effects and safety concerns

In conclusion, hydroxyzine's anticholinergic properties are clinically significant and should be carefully considered when prescribing, particularly for vulnerable populations such as older adults and those with comorbid conditions that may be exacerbated by anticholinergic effects.