Histamine Antagonists
Histamine is a chemical messenger mostly generated in mast cells. Histamine, via multiple receptor systems, mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in parts of the brain.
Classification
- H1 receptor blockers
- First-generation: Diphenhydramine, chlorpheniramine, promethazine
- Second-generation: Cetirizine, loratadine, fexofenadine (less or no CNS penetration, thus non-sedating)
- H2 receptor blockers: Cimetidine, ranitidine, famotidine, nizatidine
- Mast cell stabilizers: Ketotifen
Pharmacodynamics
Histamine antagonists function by blocking the action of histamine at its receptors:
- H1 receptor blockers (located in endothelial cells and smooth muscles):
- First-generation H1 blockers competitively inhibit histamine at H1 receptors. These drugs can cross the blood-brain barrier, leading to sedative effects.
- Second-generation H1 blockers have minimal or no CNS penetration, reducing sedation.
- H2 receptor blockers (located on parietal cells in the stomach lining):
- By blocking histamine at H2 receptors, they reduce gastric acid secretion, making them effective for peptic ulcer disease, GERD, and Zollinger-Ellison syndrome.
- By decreasing stomach acid production, they help to promote the healing of gastric and duodenal mucosa.
- Ketotifen, a mast cell stabilizer:
- Prevents the release of histamine and other inflammatory mediators by inhibiting Ca²⁺ influx into mast cells.
- Used in allergic and inflammatory conditions such as asthma, allergic conjunctivitis, and atopic dermatitis.