Histamine and antihistamine drugs

1. Histamine and antihistamine drugs Department of pharmacology Liming zhou 2010,spring

2. Introduction Autacoids • histamine • serotonin • endogenous peptides • prostaglandins • leukotrienes

3. Introduction Distribution: The primary site the mast cell granules (or basophils)  • Mast cells are important in that they release histamine in response to potential tissue injury Other sites • central nervous system :neurotransmitter • the fundus of the stomach: major acid secretagogues

4. Histamine: Storage and Release Immunologic Release:  • The most important mechanism for histamine release is in response to an immunological stimulus.  • In mast cells, if sensitized by surface IgE antibodies, degranulate when exposed specific antigen.  • Degranulation means liberation of the contents of the mast cell granules, including histamine.  • Degranulation is involved in the immediate (type I) allergic reaction.

5. Mechanical/Chemical Release: • A second type of release occurs following chemical or mechanical injury to mast cells.  • In these injuries caused degranulation

6. Mechanism of Action – • Histamine mediates its effects by interacting with receptors.  • Receptor Types   H1, H2,and H3 types. 

7. Pharmalogical effects of Histamine 1)Histamine promotes( intestinal and Bronchiolar ) smooth muscle contraction which is an H1 receptor mediated effect 2)Histamine significant increase in gastric acid and gastric pepsin secretion which is an H2 receptor mediated effect 3) Vasodilation of arterioles and precapillary sphincters which is an H1and H2 receptor mediated effect

8. Increase the systole dilation the small vein and small artery • Increase the gastric acid secretion • Mainly contract the soomth muscle,especially in bronchus

9. Histamine antagonists receptor antagonists: • selective blockade of histamine receptors (H1, H2, H3 types)

10. H1 receptor antagonists First-generation • diphenhydramine • promethazine • chlorpheniramine Second-generation • orally active, hepatic metabolism • H1 receptor blockers: competitive antagonism

11. Therapeutic uses 1）Allergic Reactions: • allergic rhinitis , Atopic dermatitis, hay fever, urticaria(风疹） 2）Motion sikness: vestibular disturbances

12. Therapeutic uses 3)Sedation and hypnotics. : • these agents to be used has sleep-aids, i.e. hypnotics.  • The newer H1 antagonists, by contrast, cause minimal or no sedation.

13. adverse effect • 1) Inhibition of CNS • 2) Some first-generation H1 antagonists have strong antimuscarinic actions (atropine-like effects) • 3) others: Second-generation overdosage: may induce cardiac arrhythmias

14. H2 receptor antangnists • Cimetidine (Tagamet) • Ranitidine (Zantac) • Famotidine (Pepcid)

15. Clinical uses • Peptic Ulcer and Duodenal Disease • Gastric Ulcer: reduce symptoms promote healing for benign gastric ulcers • Gastroesophageal Reflux Disorder (erosive esophagitis)

16. Clinical uses Hypersecretory Disease: •   Zollinger-Ellison syndrome: • acid hypersecretion -- caused by gastrin-secreting tumor • Systemic mastocytosis and multiple endocrine adenomas:

17. adverse effects Generally well tolerated • Most common adverse effects: diarrhea , dizziness , somnolence , headache , rash, thrombocytopenia , neutropenia , aplastic anemia)

18. adverse effects • cimetidine --------CNS effects (uncommon): elderly: confusion states, delirium, slurred speech (most associated with cimetadine) • ---------antiandrogenic effects • ---------Blood Dyscrasias (granulocytopenia , thrombocytopenia , neutropenia , aplastic anemia)