Download 胆碱受体激动药

Cholinoceptoractivating drug
Cholinoceptor-activating
drug
• Acetylcholine receptor stimulants
• Cholinesterase inhibitors
• Mimic acetylocholine
Acetylcholine receptor
stimulants
• Classified by their spectrum of
action depending on the receptor
type
• Activate muscarinic receptor
• Activate nicotinic receptor
Muscarinic receptor
stimulants
• Choline esters: acetylcholine,
methacholine, carbachol,
bethanechol
• Alkaloid: pilocarpine, arecoline
Acetylcholine
• Cardiovascular system:
– Vessel: dilation via EDRF
– Negative chronotropic effect
– Negative dromotropic effect
– Negative inotropic effect
Acetylcholine
• Gastrointestinal tract: increase
motility, stimulate secretion
• Urinary bladder: detrusor
contraction, trigone and sphincter
relaxation
• Glands: stimulate secretion
• Eye: contract sphincter muscle of
iris, contract ciliary muscle for
near vision
Acetylcholine
• A large dose of Ach after
administration of atropine can
activate nicotinic receptor
• N1: ganglion
• N2: neuromuscular junction
Activate NN
receptor
• All ganglion are activated
• Sympathetic effects: increase in blood
pressure
• Parasympathetic effects: glands secret,
contract smooth muscle
• excite adrenal gland medulla
• Overdose: excitement
inhibition
Activate Nm receptor
• Neuromuscular end plate
• Skeletal muscle Contraction
methacholine
• Selectively activate muscarinic
receptor
• Stronger effects on cardiovascular
system
• Clinical uses: sjogren’s syndrome
• Asthma, ulcer, anoxemia
others
• Carbachol: pharmacodynamics is
similar to Ach, uses for
glaucoma
• Bethanechol: more selective to
M receptor
Alkaloid
Including pilocarpine, arecoline,
muscarine, oxotremorine
pilocarpine
• Pharmacodynamics:
– Eye: miosis, ocular pressure
reduction, accommodation
– Glands: secretion
阿托品阻断
毛果芸香碱激动
M受体
瞳孔括约肌
缩瞳
（动眼神经的胆碱能神经支配）
瞳孔开大肌
（去甲状腺素能神经支配）
Α受体
扩瞳
虹膜(包括瞳孔括约肌和瞳孔开大肌 )
毛果芸香碱的缩瞳作用
睫状体上皮
细胞分泌
狭窄时眼内
压增高，闭
角型青光眼
（急，慢型
充血性青光
眼）
房水
前房角间隙
间隙扩大,房
水入循环
变性或硬化
时眼内压增
高 开角性
青光眼（慢
性单纯性青
光眼）
血管
渗出
瞳孔
毛果芸香碱收
缩瞳孔括约肌
前房
缩瞳虹膜拉紧
虹膜根部变薄
降低眼内压
小梁网
毛果芸香碱
巩膜静脉窦
收缩睫状肌
扩张小血管
阿托品扩瞳，虹膜退向四周，前房角
血流
间隙变窄，房水回流受阻，眼内压升高
毛果芸香碱的降低眼内压作用
正常时晶体较扁平
受睫状肌控制
环状肌
(瞳孔括约肌)
辐射状肌
(瞳孔开大肌)
睫状肌起点
动眼神经兴奋
悬韧带 或毛果芸香碱
外
界
动眼神经胆
碱能神经
向瞳孔中心收缩悬韧
带，睫状小带放松
晶状体变凸
屈光度增加
只视近物(调节痉挛)
阿
托
品
去甲肾上腺素能
神经支配 对眼
调节无重要意义
睫状肌松弛而退向
外缘，悬韧带拉紧
晶状体变扁
屈光度降低
只视远物(调节麻痹)
毛果芸香碱的调节痉挛作用
Clinical uses
• Glaucoma
• Iritis
Muscarine
Direct acting muscarinic
receptor: toxic reaction
nicotine
• Contributes to increased risk of
vascular disease and sudden
coronary death
• Contributes to high incidence of
ulcer recurrence with peptic
ulcer
Anticholinesterase
agents
Acetylcholinesterase
Ach====AchE
Ach- AchE
choline+AcAchE
Acetate+Ache
The entire process takes place in 150ms
AchE
• Nerve terminal, synaptic
cleft, effectors
• Most chlinergic synapses are
richly supplied with AchE,
the half-life of Ach is very
short
Anticholinesterase
agents
• Binds to AchE
complex
• The covalent bond is resistance
to the second process, and this
step is prolonged
classification
• Hydration process is
prolonged for 30 minutes to 6
hours
• Hydration process is
prolonged for hundreds of
hours
Anticholinesterase
agents
• Pharmacodynamics:
– Eye: miosis, ocular pressure
reduction, accommodation
– Gastrointerase systems:
contract, increase secretion
Anticholinesterase
agents
• Neuromuscular junction:
– Therapeutic concentration:
prolong and intensify the actions
of Ach; activate skeletal muscle
directly
– Higher concentration: fibrillation
of muscle fibers
Anticholinesterase
agents
• Respiratory, urinary tract:
contract
• Cardiovascular system: increase
activation in ganglia and at
acetylcholine receptors on
neruoeffector cells( HR ,BP )
Anticholinesterase
agents
• Glands: secret
• CNS
– Low concentration: activation of
EEG, subjective alerting response
– High concentration: coma,
respiratory arrest
Clinical uses
•
•
•
•
•
•
Myasthenia gravis
Ileus,
Glaucoma
Detoxifcation
Alzheimier’s disease
cholinergic crisis
Neostigmine
• Inhibit AchE and thereby increase
the concentration of endogenous
Ach
• Act at neuromuscular junction and
smooth muscle Selectively
• Myasthenia gravis
• Ileus,
Pyridostigmine
• Pharmacodynamics is similar to
Neostigmine
• Take effect slowly
• Myasthenia gravis
• Ileus,
physostigmine
• Eye
• CNS: toxic reaction
• glaucoma
• Edrophonium chloride: Use for
diagnosis
• Ambenonium chloride:
• Galanthamine
• Demecarium bromide
Organophosphates
• Binds to AchE
complex
• The covalent bond is stable and
hydrolyzes in water at a very
slow rate
• Aging: more stable and more
difficult to split
Toxic symptom
• Activate M receptor
• Activate N receptor
• CNS
• Diagnosis
• Prevention
• Detoxifcation
– Atropine
– PAM