Transcript Histamine and antihistamine drugs

Histamine and antihistamine
drugs
Department of pharmacology
Liming zhou
2010,spring
Introduction
Autacoids
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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 H1, H2,and H3 types.
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
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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 (H1, H2, H3 types)
H1 receptor antagonists
First-generation
 diphenhydramine
 promethazine
 chlorpheniramine
Second-generation
 orally active, hepatic metabolism
 H1 receptor blockers: competitive
antagonism
Therapeutic uses
1）Allergic Reactions:
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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 H1 antagonists, by contrast,
cause minimal or no sedation.
adverse effect
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1) Inhibition of CNS
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2) Some first-generation H1 antagonists
have strong antimuscarinic actions
(atropine-like effects)
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3) others: Second-generation overdosage:
may induce cardiac arrhythmias
H2 receptor antangnists
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Cimetidine (Tagamet)
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Ranitidine (Zantac)
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Famotidine (Pepcid)
Clinical uses
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Peptic Ulcer and Duodenal Disease
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Gastric Ulcer: reduce symptoms
promote healing for benign gastric ulcers
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Gastroesophageal Reflux Disorder
(erosive esophagitis)
Clinical uses
Hypersecretory Disease:
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Zollinger-Ellison syndrome:
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acid hypersecretion -- caused by
gastrin-secreting tumor
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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
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cimetidine --------CNS effects
(uncommon): elderly: confusion states,
delirium, slurred speech (most associated
with cimetadine)
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---------antiandrogenic effects
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---------Blood Dyscrasias
(granulocytopenia , thrombocytopenia ,
neutropenia , aplastic anemia)