胆碱受体激动药英文课件.ppt

1、 Cholinoceptor-activating drugCholinoceptor-activating drug Acetylcholine receptor stimulants Cholinesterase inhibitors Mimic acetylocholineAcetylcholine receptor stimulants Classified by their spectrum of action depending on the receptor type Activate muscarinic receptor Activate nicotinic receptor

2、Muscarinic receptor stimulants Choline esters:acetylcholine,methacholine,carbachol,bethanechol Alkaloid:pilocarpine,arecolineAcetylcholine Cardiovascular system:Vessel:dilation via EDRF Negative chronotropic effect Negative dromotropic effect Negative inotropic effectAcetylcholine Gastrointestinal t

3、ract: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 visionAcetylcholine A large dose of Ach after administration of atropine can activate nic

4、otinic receptor N1:ganglion N2:neuromuscular junctionActivate 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 inhibitionActivate Nm receptor Neuromuscul

5、ar end plate Skeletal muscle Contractionmethacholine Selectively activate muscarinic receptor Stronger effects on cardiovascular system Clinical uses:sjogrens syndrome Asthma,ulcer,anoxemiaothers Carbachol:pharmacodynamics is similar to Ach,uses for glaucoma Bethanechol:more selective to M receptor

6、Alkaloid Including pilocarpine,arecoline,muscarine,oxotremorinepilocarpine Pharmacodynamics:Eye:miosis,ocular pressure reduction,accommodationGlands:secretion（动眼神经的胆碱能神经支配）（动眼神经的胆碱能神经支配）毛果芸香碱激动毛果芸香碱激动 瞳孔括约肌瞳孔括约肌 缩瞳缩瞳 阿托品阻断阿托品阻断 瞳孔开大肌瞳孔开大肌 扩瞳扩瞳（去甲状腺素能神经支配）（去甲状腺素能神经支配）虹膜虹膜(包括瞳孔括约肌和瞳孔开大肌包括瞳孔括约肌和瞳孔开大肌 )

7、毛果芸香碱的缩瞳作用毛果芸香碱的缩瞳作用 受体受体 M受体受体狭窄时眼内狭窄时眼内压增高，闭压增高，闭角型青光眼角型青光眼（急，慢型（急，慢型充血性青光充血性青光眼）眼）变性或硬化变性或硬化时眼内压增时眼内压增高高 开角性开角性青光眼（慢青光眼（慢性单纯性青性单纯性青光眼）光眼）睫状体上皮睫状体上皮 细胞分泌细胞分泌血管血管渗出渗出 房水房水 瞳孔瞳孔 前前房房前房角间隙前房角间隙小梁网小梁网巩膜静脉窦巩膜静脉窦血流血流 毛果芸香碱的降低眼内压作用毛果芸香碱的降低眼内压作用 间隙扩大间隙扩大,房房水入循环水入循环毛果芸香碱收毛果芸香碱收缩瞳孔括约肌缩瞳孔括约肌 缩瞳虹膜拉紧缩瞳虹膜拉紧 虹膜根

8、部变薄虹膜根部变薄毛果芸香碱毛果芸香碱收缩睫状肌收缩睫状肌扩张小血管扩张小血管阿托品扩瞳，虹膜退向四周，前房角阿托品扩瞳，虹膜退向四周，前房角间隙变窄，房水回流受阻，眼内压升高间隙变窄，房水回流受阻，眼内压升高 降低眼内压降低眼内压正常时晶体较扁平正常时晶体较扁平受睫状肌控制受睫状肌控制环状肌环状肌辐射状肌辐射状肌(瞳孔括约肌瞳孔括约肌)动眼神经兴奋动眼神经兴奋或毛果芸香碱或毛果芸香碱动眼神经胆动眼神经胆碱能神经碱能神经阿托品阿托品向瞳孔中心收缩悬韧向瞳孔中心收缩悬韧带，睫状小带放松带，睫状小带放松睫状肌松弛而退向睫状肌松弛而退向外缘，悬韧带拉紧外缘，悬韧带拉紧(瞳孔开大肌瞳孔开大肌)去甲肾上

9、腺素能去甲肾上腺素能神经支配神经支配 对眼对眼调节无重要意义调节无重要意义只视近物只视近物(调节痉挛调节痉挛)只视远物只视远物(调节麻痹调节麻痹)晶状体变扁晶状体变扁屈光度降低屈光度降低晶状体变凸晶状体变凸屈光度增加屈光度增加毛果芸香碱的调节痉挛作用毛果芸香碱的调节痉挛作用外外界界睫状肌起点睫状肌起点悬韧带悬韧带Clinical uses Glaucoma IritisMuscarine Direct acting muscarinic receptor:toxic reactionnicotine Contributes to increased risk of vascular disea

10、se and sudden coronary death Contributes to high incidence of ulcer recurrence with peptic ulcer AcetylcholinesteraseAch=AchE Ach-AchE choline+AcAchE Acetate+AcheThe entire process takes place in 150ms AchE Nerve terminal,synaptic cleft,effectors Most chlinergic synapses are richly supplied with Ach

11、E,the half-life of Ach is very shortAnticholinesterase agents Binds to AchE complex The covalent bond is resistance to the second process,and this step is prolongedclassification Hydration process is prolonged for 30 minutes to 6 hours Hydration process is prolonged for hundreds of hoursAnticholines

12、terase agents Pharmacodynamics:Eye:miosis,ocular pressure reduction,accommodationGastrointerase systems:contract,increase secretionAnticholinesterase agents Neuromuscular junction:Therapeutic concentration:prolong and intensify the actions of Ach;activate skeletal muscle directly Higher concentratio

13、n:fibrillation of muscle fibersAnticholinesterase 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 al

14、erting response High concentration:coma,respiratory arrestClinical uses Myasthenia gravis Ileus,Glaucoma Detoxifcation Alzheimiers disease cholinergic crisisNeostigmine Inhibit AchE and thereby increase the concentration of endogenous Ach Act at neuromuscular junction and smooth muscle Selectively M

15、yasthenia 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 bromideOrganophosphates 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 splitToxic symptomActivate M receptorActivate N receptorCNSDiagnosisPreventionDetoxifcationAtropinePAM