What are the first and second generation antihistamines (anti-histamine)?

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From the Guidelines

First-generation antihistamines include diphenhydramine, hydroxyzine, and clemastine, while second-generation antihistamines include loratadine, cetirizine, fexofenadine, desloratadine, levocetirizine, and bilastine.

Classification of Antihistamines

Antihistamines are classified into first and second generation categories based on their chemical structure, side effect profile, and blood-brain barrier penetration.

  • First-generation antihistamines readily cross the blood-brain barrier, causing sedation and other central nervous system effects, as well as anticholinergic properties that can cause dry mouth, urinary retention, and blurred vision 1.
  • Second-generation antihistamines minimally cross the blood-brain barrier, resulting in significantly less sedation, and have fewer anticholinergic effects and drug interactions, making them safer options for elderly patients and those with comorbidities 1.

Examples of First and Second Generation Antihistamines

  • First-generation antihistamines:
    • diphenhydramine (Benadryl)
    • chlorpheniramine
    • hydroxyzine
    • promethazine
    • clemastine
    • doxylamine
  • Second-generation antihistamines:
    • loratadine (Claritin)
    • cetirizine (Zyrtec)
    • fexofenadine (Allegra)
    • desloratadine (Clarinex)
    • levocetirizine (Xyzal)
    • bilastine

Sedative Properties of Second-Generation Antihistamines

There are important differences among the second-generation antihistamines in regards to their sedative properties, with fexofenadine, loratadine, and desloratadine not causing sedation at recommended doses, while cetirizine and intranasal azelastine may cause sedation at recommended doses 1.

From the FDA Drug Label

Brompheniramine maleate is a histamine antagonist, specifically an H1-receptor-blocking agent belonging to the alkylamine class of antihistamines. Fexofenadine hydrochloride is a histamine H1-receptor antagonist

  • First generation antihistamine:
    • Brompheniramine
  • Second generation antihistamine:
    • Fexofenadine 2 3

From the Research

First Generation Antihistamines

  • Diphenhydramine 4, 5, 6
  • Chlorpheniramine 4
  • Brompheniramine 4
  • Hydroxyzine 6

Second Generation Antihistamines

  • Loratadine 4, 5
  • Desloratadine 4, 5
  • Cetirizine 4, 5
  • Fexofenadine 4, 5

Professional Medical Disclaimer

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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