What are first-generation antihistamines (Histamine 1 receptor antagonists)?

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From the Guidelines

First generation antihistamines are a class of medications that include diphenhydramine, hydroxyzine, and clemastine, which are associated with sedative effects, anticholinergic properties, and significant potential to cause performance impairment and adverse effects. These medications work by blocking histamine H1 receptors to treat allergic symptoms, but they commonly cause sedation as they cross the blood-brain barrier 1. Examples of first generation antihistamines include:

  • Diphenhydramine (Benadryl)
  • Hydroxyzine
  • Clemastine
  • Chlorpheniramine
  • Promethazine
  • Dimenhydrinate

These medications typically work within 15-30 minutes and last 4-6 hours, with dosing varying by specific drug (e.g., diphenhydramine 25-50mg every 4-6 hours) 1. While effective for allergies, hives, and motion sickness, their anticholinergic properties cause significant side effects including:

  • Drowsiness
  • Dry mouth
  • Blurred vision
  • Urinary retention
  • Constipation

They should be used cautiously in the elderly and those with glaucoma, prostate issues, or certain heart conditions, as they are more sensitive to the psychomotor impairment promoted by first-generation antihistamines and are at increased risk for complications such as fractures and subdural hematomas caused by falls 1. Due to their sedating properties, they're often used in sleep aids and should not be combined with alcohol or other central nervous system depressants. The use of first-generation antihistamines should be approached with caution, and alternative antihistamines with a lower likelihood of adverse effects should be considered 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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