General physiology

Target: histamine H1 receptors

• Location of H1 receptors
  • Smooth muscles (especially bronchial and nasopharyngeal lining)
  • Vascular endothelial cell surfaces
  • Central nervous system
• Histamine effects on H1 receptors
  • ↑ Capillary dilation and permeability → hypotension and edema
  • ↑ Bronchiolar smooth muscle contraction (via IP3 and DAG release) → bronchoconstriction
  • ↑ Nasal and bronchial mucus production

Target: histamine H2 receptors

• Location of H2 receptors
  • Gastric parietal cells (oxyntic cells)
• Histamine effects on H2 receptors
  • Increased gastric acid secretion

H1 antihistamines

First-generation antihistamines

• Drug
  • Diphenhydramine
  • Meclizine
  • Doxylamine
  • Promethazine
  • Clemastine
  • Dimenhydrinate
  • Chlorpheniramine
  • Dimetindene
• Uses
  • Antiallergic agent
    • Allergic rhinitis and conjunctivitis
    • Contact dermatitis
    • Hay fever, urticaria, angioedema, and rhinorrhea
  • Antiemetic agent
  • Sedative agent
  • Anaphylactic shock
  • Motion sickness
• Characteristics
  • Strong sedative action
  • Anticholinergic effects, e.g., dry mouth and eyes, mydriasis, urinary retention, tachycardia, dizziness, tinnitus (mostly with first-generation antihistamines)
  • Anti-α-adrenergic effects, e.g, postural hypotension (can lead to falls), weight gain

Second-generation antihistamines

• Drug
  • Loratadine
  • Desloratadine
  • Cetirizine
  • Fexofenadine
    • Fox, satyr, and rat: 2nd generation H1 blockers, Fexofenadine, cetirizine, loratadine
• Uses
  • Antiallergic agent
• Characteristics
  • Nonsedative/mildly sedative
    • These antihistamines usually do not cross the blood-brain barrier and act mainly outside the central nervous system.

H2 antihistamines

• Drug
  • Cimetidine
  • Famotidine
  • Nizatidine
• Uses
  • To reduce production of stomach acid
• Characteristics
  • Usually used as second-line treatment or in combination with proton pump inhibitors (PPIs)