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Chapter 30
Drugs affecting autacoids
Local hormones
 Prostaglandins, histamine and serotonin
belong to a group of compounds called
autacoids. Although differed in structures
and pharmacologic activities, they all have
the common feature of being formed by the
tissues on which they act; thus, they act as
local hormones.
 In this chapter, we are going to discuss
histamine and histamine antagonists mainly.
Section 1 Arachidonic
acid and it’s productions
Ⅰ、Prostaglandins (PGs)
Alprostadil (PGE1)
Epoprostenol (PGI2)
Misprostol
Enprostil（恩前列素）
Ⅱ、LTs and LTs inhibitors
1、LTs
2、LTs inhibitors
Ⅲ、PAF and it’s antagonists
1、PAF（血小板活化因子）
2、PAF receptor antagonists
Section 2
5-HT and antagonists
Ⅰ、5-HT
Ⅱ、5-HT receptor agonists
sumatriptan（舒马普坦）
buspirone（丁螺环酮）
cisapride（西沙必利）
dexfenfluramine（右芬氟
拉明）
Ⅲ、5-HT receptor antagonists
Cyproheptadine （赛庚啶）
Ondansetron （昂丹司琼）
Ergot alkaloids
1.peptide alkaloids
Ergotamine（麦角胺）
ergotoxine（麦角毒）
2. Amine alkaloids
ergonovine（麦角新碱）
methylergonovine（甲基麦角
新碱）
methysergide（二甲麦角新碱）
Section 4
Polypeptides
Ⅰ、kinins
1、bradykinin (BK)
2、kinin inhibitors
aprotinin（抑酞酶）
icatibant（艾替班特）
Ⅱ、endothelins (ETs)
1、 Ets
2、 Ets inhibitors
Ⅲ、substance (SP)
Section 5 Nitric oxide (NO)
Section 6 Adenosine
Section 3 Histamine and
receptor antagonists
Ⅰ． Histamine
 Histamine is a chemical messenger that
mediates a wide range of cellular response,
including:
 allergic reactions
 Local inflammatory reactions
 gastric acid secretion
 cardiovascular function
 possibly neuro-transmission in parts of the brain.
Metabolism of histamine
(1) Synthesis
Histidine
histamine
(2) Storage and release of histamine
stored in mast cell and basophil
Histamine
methylhistamine
methylimidozoleacetic
acid
[Mechanism of actions]
Three types of histamine receptors:
H1, H2 and H3-R
 H1 receptors are important in
producing smooth muscle contraction
increasing capillary permeability
Dilating vascular smooth muscle
Stimulating sensory nerve ending
 H2 receptors
mediate gastric acid secretion
Dilating vascular smooth muscle
Increase heart rate and contractility
 H3 receptors is located in presynaptic
membrane and possibly mediate the
negative feedback of histamine release.
Action of histamine
pharmacological effects
1. Cardiovascular system:
(1)heart: positive inotropism----H1,H2-R
positive chronotropism----H2-R
(2)vessel: dilation BP↓
 In small doses, the cardiovascular effect
of histamine is mainly mediated by H1receptors.
 In large doses, the cardiovascular effect
of histamine is mainly mediated by both
H1 and H2-receptors.
 ( 3) triple effect on terminal vasculature
(itching & pain):
 i. reddening at injection site due to
vasodilation
 ii. wheal or disk of edema within 1 to 2 min
 iii. a large, bright crimson flare or halo
surrounding the wheal
Pharmacological effects
2. splanchnic smooth muscle: histamine
causes bronchiolar and gastrointestinal tract
smooth muscle constriction which is
mediated by H1 receptors.
3. Exocrine system:
histamine has long been recognized as a
powerful stimulant of gastric acid secretion which
is caused by activation of H2-receptors on gastric
parietal cells.
secretion of nasal and bronchial mucus are
also increased.
it enhances salivary and lacrimal gland
secretion (minimal unless large doses are given)
Pharmacological effects
4. nervous system: histamine is a powerful
stimulant of sensory nerve endings,
especially those mediating pain and itch.
This H1-receptor-mediated effect is an
important component of some allergic
reactions .
clinical uses
mainly for diagnosis
(1) Testing the secretion of gastric
acid
(2) Diagnosis of pheochromocytoma
(3) Pulmonary function testing
(4) Tool drugs
Betahistine (培他司汀，抗眩啶）
Histamine Antagonists
H1 receptor antagonists have a history
for over 60 years. The first H2 receptor
antagonist was reported in 1972, while
selective H3 receptor antagonists are
not yet available for clinical use.
H1 receptor antagonists
Pharmacological effects
1.H1 receptor blockade
(1) capiliary
(2) BP
(3) GI SM
(4) branchial SM
H1 receptor antagonists
2.Actions not caused by histamine
receptor blockade
(1) Sedative and hypnotic effects
(2) Antiemetic（止吐） action
(3) Anticholinoceptor actions
Therapeutic uses
1. Skin and mucosa allergic conditions：
H1 blockers are useful in treating allergies
caused by antigens acting on IgE-antibody
sensitized mast cells, including:
Allergic rhinitis(鼻炎), urticaria(荨麻疹),
pollen disease, hay fever, atopic dermatitis ,
contact dermatitis , drug rash
low efficacy on asthma
ineffective on alergic shock
Therapeutic uses
 2. motion sickness and nausea:
some H1 receptor antagonists, such as
diphenhydramine (DH) and
dimenhydrinate (乘晕宁) are the most
effective agents for the prevention of the
symptoms of motion sickness.
 3. insomnia: some of the H1 receptor
antagonists, such as DH and promethazine,
have strong sedative properties.
 4. other use: promethazine
adverse reactions
H1 receptor antagonists have a low specificity,
that is, they interact not only with histamine
receptor but also with muscarinic cholinergic
receptors, α-adrenergic receptors and serotonin
receptors.
 1. CNS reactions:
Sedation, somnolence, hypodynamia the most
frequently observed reactions, but less common
in some new agents for they do not enter the
CNS.
 2.gestraintestinal reaction: dry mouth,
anorexia, constipation, diarrea
H2 receptor antagonists
Effects
(1) Reduce the secretion of gastric
acid.
(2) Other effects related to H2
receptor blockade
1) Cardiovascular system
2) Immunoregulation effects
uses
 The chief clinical use for histamine H2
receptor antagonists is as inhibitors of
gastric acid secretion in the treatment of
peptic ulcers. We will discuss it in other
chapter.
H3 receptor blockers
Burimamide
GT2277