Medicine & USMLE

First Generation Antihistamines (Diphenhydramine)

In Progress
  1. Terbutaline
  2. Radioactive Iodine
  3. Ipratropium / Tiotropium
  4. Levothyroxine
  5. Second Generation Antihistamines
  6. First Generation Antihistamines (Diphenhydramine)
  7. Inhaled Steroids
  8. Antitussives
  9. Hypokalemia


First generation antihistamines include the drugs diphenhydramine, promethazine, and chlorpheniramine. They are used to treat mild allergic reactions and allergies, as well as nausea. Side effects include drowsiness and anticholinergic side effects including constipation, tachycardia, urinary retention, and dry mouth.

Key Points

  • First Generation Antihistamines
    • Key Drugs
      • Diphenhydramine (Benadryl)
      • Promethazine (Phenergan)
      • Chlorpheniramine
      • Hydroxyzine
      • Cyproheptadine
    • Mechanism
      • Antihistamine
        • Competes with histamine at the H-1 receptor sites to reduce the effects of histamine
    • Clinical Use
      • Allergic Reactions
        • Treats mild allergic reactions (e.g. hives/rash, pruritus), as well as seasonal allergies (sneezing, rhinorrhea, etc.)
        • Given with epinephrine in severe anaphylaxis
      • Nausea
        • Suppresses vomiting due to anticholinergic activity
        • Most effective for vestibular nausea (motion sickness), such as that caused by Meniere’s disease, but may also be used as a general anti-emetic
      • Can be used to treat red man syndrome caused by vancomycin
      • Insomnia (off-label)
        • Due to sedative effects
    • Side Effects and Adverse Reactions
      • Drowsiness
        • Do not drive after taking this medication
        • Do not take with other CNS depressants (alcohol, narcotics, barbiturates, etc.)
        • Use with caution in elderly due to risk of falls
      • Anticholinergic symptoms
        • Can cause delirium in older adults (see Beer’s Criteria)
        • Dry mouth
        • Urinary retention
        • Constipation
        • Blurred vision
          • Avoid in patients with glaucoma
      • Orthostatic hypotension
        • Manifests with dizziness and lightheadedness
      • GI discomfort
        • Nausea, vomiting, constipation