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

Introduction Autacoids histamine serotonin endogenous peptides prostaglandins leukotrienes

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

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.

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

Mechanism of Action – Histamine mediates its effects by interacting with receptors. Receptor Types H 1, H 2, and H 3 types.

Pharmalogical effects of Histamine 1)Histamine promotes( intestinal and Bronchiolar ) smooth muscle contraction which is an H 1 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 H 1 and H 2 receptor mediated effect

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

Histamine antagonists receptor antagonists: selective blockade of histamine receptors (H 1, H 2, H 3 types)

H1 receptor antagonists First-generation diphenhydramine promethazine chlorpheniramine Second-generation orally active, hepatic metabolism H 1 receptor blockers: competitive antagonism

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

Therapeutic uses 3)Sedation and hypnotics. : these agents to be used has sleep-aids, i.e. hypnotics. The newer H 1 antagonists, by contrast, cause minimal or no sedation.

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

H 2 receptor antangnists Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid)

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

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

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

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)