Pharmacology of Antihistamines

Introduction to Histamine

• Histamine is a small molecule produced by decarboxylation of histidine.
• Found throughout the body, concentrated in skin, lungs, and gastrointestinal tract.
• Stored in granules within mast cells, basophils, eosinophils, and enterochromaffin-like cells.

Triggers for Histamine Release

1. Allergic Reaction
   • Activation of B cells leads to formation of plasma cells producing IgE antibodies.
   • Antibodies attach to mast cells; subsequent allergen exposure triggers histamine release.
2. Tissue Injury
   • Damaged mast cells release mediators including histamine affecting blood vessels and nerves.
3. Drugs and Chemicals
   • Some drugs and chemicals displace histamine from granule stores (e.g., venoms, morphine).

Histamine Receptors

• Four types: H1, H2, H3, H4.
• Focus on H1 and H2 receptors as primary targets for drugs.

H1 Receptors

• Located on vascular endothelial cells, smooth muscle cells, brain, and peripheral nerve endings.
• Mediate inflammatory and allergic reactions (redness, edema, bronchoconstriction).
• Central effects include wakefulness and appetite suppression; peripheral effects include pain and itching.

H2 Receptors

• Found on gastric parietal cells.
• Stimulation increases gastric acid secretion.

Antihistamines

H1 Receptor Blockers (Antihistamines)

• First-generation: Cross blood-brain barrier, cause sedation, and have non-selective receptor effects (dry mouth, hypotension, increased appetite).

  • Examples: Brompheniramine, chlorpheniramine, diphenhydramine, etc.
  • Uses include allergy symptom relief, insomnia (e.g., diphenhydramine), and motion sickness (e.g., meclizine).

• Second-generation: Bulkier structure, limited blood-brain barrier crossing, more selective for peripheral receptors, fewer sedative effects.

  • Examples: Cetirizine, loratadine, fexofenadine, etc.
  • Include drugs with antihistamine and mast cell stabilizing effects (e.g., azelastine).

H2 Receptor Blockers (H2 Antagonists)

• Target acid-producing parietal cells in the stomach, reduce gastric acid secretion.
• Useful for gastric ulcers and GERD.
• Examples: Cimetidine, famotidine, ranitidine, nizatidine.
• Generally well-tolerated; cimetidine may cause interactions and side effects like gynecomastia.

Conclusion

• Comprehensive understanding of histamine function and the pharmacology of antihistamines.
• Acknowledgement of drug classes and their therapeutic uses.