What are the drugs that belong to sedating antihistamines?

Sedating Antihistamines: Classification and Clinical Considerations

First-generation antihistamines are the primary drugs that belong to the sedating antihistamine class, including diphenhydramine, hydroxyzine, chlorpheniramine, promethazine, cyproheptadine, ketotifen, and doxepin. 1

First-Generation (Sedating) Antihistamines

First-generation H1 receptor antihistamines are characterized by:

• Significant sedative effects due to their ability to cross the blood-brain barrier 2
• Anticholinergic effects that can lead to cognitive impairment 1
• Extensive hepatic metabolism requiring dose adjustments in liver disease 3

Common Sedating Antihistamines:

1. Diphenhydramine

   • Causes significant sedation and impairment of psychomotor performance 4
   • Associated with cognitive decline, particularly in elderly patients 1
   • Can impair driving ability 1

2. Hydroxyzine

   • Highly sedating with extended anticholinergic effects 1
   • Contraindicated during early pregnancy 3
   • Requires caution in patients with renal or liver impairment 3

3. Chlorpheniramine

   • Produces significant impairments in early morning behavior 5
   • Impairs critical flicker fusion thresholds (measure of CNS arousal) 5

4. Promethazine

   • Highly sedating with significant CNS depression 6
   • Produces impairments in early morning behavior 5

5. Cyproheptadine

   • Sedating H1 antihistamine with extended anticholinergic and antiserotonergic activities 1
   • May help with gastrointestinal symptoms in mast cell disorders 1

6. Ketotifen

   • Sedating H1 receptor antagonist 1
   • Approved in the US for allergic eye disease but can be compounded as tablets 1

7. Doxepin

   • Potent H1 and H2 antihistamine with tricyclic antidepressant activity 1
   • Can cause drowsiness and cognitive decline, particularly in the elderly 1
   • May increase suicidal tendencies in children and young adults with depression 1

Clinical Considerations and Cautions

Adverse Effects of Sedating Antihistamines:

• Sedation and impaired cognition: First-generation antihistamines significantly impair psychomotor performance and cognitive function 4
• Cardiovascular effects: Some sedating antihistamines may have cardiac effects 6
• Elderly patients: Increased risk of cognitive decline, falls, and anticholinergic effects 1, 3
• Children: Associated with impaired learning and school performance 3
• Occupational hazards: Increased risk of accidents and impaired driving ability 3

Alternatives to Sedating Antihistamines:

Second-generation (non-sedating) antihistamines are preferred when sedation is a concern:

• Cetirizine (may cause mild sedation in some patients) 7
• Loratadine 7
• Fexofenadine (least sedating of the second-generation options) 7, 4
• Desloratadine 7

Special Populations

Liver Disease:

• Avoid first-generation antihistamines due to extensive hepatic metabolism 3
• Consider second-generation antihistamines at reduced doses (typically half the standard dose) 3

Elderly:

• First-generation antihistamines can worsen cognitive function and increase fall risk 3
• Monitor for anticholinergic effects which are especially problematic in this population 1

Children:

• Sedating antihistamines have been shown to be effective in children with allergic conditions 1
• However, they can impair learning and school performance 3

Conclusion

When selecting an antihistamine, the sedating properties of first-generation agents should be carefully considered against their potential benefits. For most patients, particularly those who need to drive, operate machinery, or maintain cognitive alertness, second-generation non-sedating antihistamines are preferable despite their slightly higher cost 4.