Histamine

Summary

• Histamine is stored in most tissues and metabolised in the liver by histaminase
• Excreted in urine

• Histamine modulates the inflammatory response, particularly type I hypersensitivity reactions

• Mast cells contain histamine and release it in hypersensitivity reactions
• IgE mediates allergen-induced hypersensitivity
• Histamine is also a neurotransmitter 
• There are three common G-protein coupled receptors for histamine
• H1 receptors are found in bronchial muscle and in the CNS
• Activation of phospholipase C
• Affinity with cetirizine
• Activation increases intracellular calcium
• Increased vascular permeability
• Arteriolar dilatation
• Smooth muscle contraction
• Bronchospasm
• CNS arousal
• Note: H1 receptors mediate the type I hypersensitivity reaction
• H2 receptors are found in the stomach, heart and uterus
• Affinity with cimetidine
• Activations stimulates adenyl cyclase and a second messenger cascade, increases cAMP
• Increased pepsin and gastric acid secretion
• Increased myocardial stroke volume (positive chronotrope too)
• H3 receptors: expressed in CNS and mediate neurotransmitter release.

Antihistamines

• H1 antihistamines
• Prevent bronchial smooth muscle contraction and vascular permeability in these tissues
• Antiemetic effect on CNS tissue
• Sedative
• Anticholinergic 

• Olopatadine: selective H1-receptor antagonist (rapid onset) and inhibitor of mast cell degranulation (and prolonged duration of action)

• H2 antihistamines
• Decrease gastric acid secretion
• Inhibit cytochrome p450: decrease metabolism of some drugs