03阿托品atropine-山东大学药理学英文课件03IntroductionAChatropine.ppt
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- 03 阿托品 atropine 山东大学 药理学 英文 课件 IntroductionAChatropine
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1、pharmacologynGeneral introductionnDrugs acting on efferent nervous systemnDrugs acting on central nervous systemnDrugs acting on cardiovascular systemnDrugs acting on visceranChemotherapeutic agentsChapter 5 Intrduction to Pharmacologyof Efferent Nervous SystemZhang BinInstitute of PharmacologySchoo
2、l of MedicineShandong UniversityOrganization of Nervous systemefferent nervous system(ENS)nautonomic nervous system (vegetative nervous system)nsomatic motor nervous system Efferent neurons of the autonomic nervous systemClassification of ENS according to the released neurotransmittersvcholinergic n
3、erve:acetylcholine(Ach)vnoradrenergic nerve:noradrenaline(NA)Classification of ENSParasympathetic nerve Central nervous system Ach skeletal muscle Ach NA Ach Ach sweat glands Ach AchAch adrenal medullasomatic motor nerve sympathetic nerveglands,smooth muscle,heart heart,vessel,smooth muscleSection 1
4、 Neurotransmitter and Receptor of ENS nNeurotransmitter of ENSnThe receptors of ENS 一.Neurotransmitter of ENS1.Development of neurotransmitter theoryn100 years ago Chemical transmission electronic transmissionn1946 Von Euler NA(noradrenaline)n1921 loewi double frog heart experimentn1926 Dale Ach(ace
5、tylcholine)2.Biosynthesis,storage,release and termination of neurotransmittersnAch(acetylcholine)nNA(noradrenaline)inhibitor2.Biosynthesis,storage,release and termination of neurotransmitters(1)Biosynthesisncholine+acetyl coenzymeA Achntyrosine dopa DA NAcholine acetylaseTHDD DH(2)Storage +ATP+prote
6、in store in vesicles Ach NA(3)releasenexocytosisnquantal realeasen cotransmission(4)TerminationvAch:acetylcholinesterase(AchE)in synapsevNA:uptake1(neuronal uptake)75%-90%storage in vesicles MAO uptake2(non-neuronal uptake)COMTMAO 二二.The receptors of ENS Classification,Distribution and Effect Cholin
7、e receptors (Cholinoceptors)nM-R:muscarinenN-R:nicotine Cholinoceptors M-R:vM1-R:ganglion,CNSvM2-R:heart,presynaptic sites(negative feedback),CNSvM3-R:exocrine glands,smooth muscle,endothelium,CNSvM4 R:exocrine glands,smooth muscle,CNSvM5-R:CNSCholinoceptorsN-R:nicotine NM-R:skeletal muscle NN-R:gan
8、glion and CNSadrenoceptor:NA AD-Rn1-R:postsynaptic effector cells (especially smooth muscle)n2-R:presynaptic nerve terminals(negative feedback),platelet,smooth muscle,lipocytesadrenoceptor-Rv1-R:postsynaptic effector cells,(especially heart,lipocytes,)presynaptic nerve terminalsv2-R:postsynaptic eff
9、ector cells,(especially smooth muscle)v3-R:postsynaptic effector cells,(especially lipocytes)Classification of receptor according to their structurenG-protein-coupled receptor:-R,-R,M-R,DA-R,5-HT-RnLigand-gated receptors N-RStructure of G-protein-coupled ReceptorMolecular Mechanism of Gq-protein-cou
10、pled ReceptorMolecular Mechanism of Gi/s-protein-coupled ReceptorStructure of ligand-gated ion channel ReceptorMolecular Mechanism of ligand-gated ion channel receptorn1.Cholinoceptors M-R:G-protein-coupled receptor M1-R:Gq-protein-coupled receptor M2-R-Gi-protein-coupled receptor N-R:ligand-gated i
11、on channel receptorn2.adrenoceptor:G-protein-coupled receptor 1 R:Gq-protein-coupled receptor 2 R:Gi-protein-coupled receptor -R:Gs-protein-coupled receptorMolecular Mechanism of Receptor N-R Na+,K+,Ca2+G-protein-coupled receptor ligand-gated receptor:(-)PKA cAMPM1-R M2-R GqGi K+,Ca2+(-)AC cAMPPLC I
12、P3DAG1-R 2-R-R(+)AC(-)AC GiGqPLC,PLA2,PLD Gs cAMP(-)PKA(+)PKA Ca2+(+)PKCterminologynadrenergic nadrenergic receptor ncholinergicncholinergic receptornpostsynaptic receptornpresynaptic receptorSection 2The physiological actions of ENSnCo-innervation and Dominant TheorynSympathetic actions:fight and f
13、light responsenParasympathetic actions:rest and digest responseSection 3 The basic mechanisms of actions of ENS drugs n1.Direct action of receptors agonist blocker(antagonist)n2.lnfluence of neurotransmitters biosynthesis release storage conversionSection 4 The classification of the ENS drugs(三)抗胆碱酯
14、酶药Chapter 6 parasympathomimeticsnCholinoceptor agonists(cholinomimetics)nAnticholinesterase agents(cholinesterase-inhibiting drugs)nDrugs of enhancers of ACh releaseCholinoceptor AgonistsM-R agonists:Choline esters:acetylcholine(ACh)alkaloids:pilocarpineN-R agonists:nicotine Section 1 M-R agonists A
15、cetylcholine(ACh)1.unstable2.low selectivity3.administration routePharmacological actions Directly activate M-R,N-Rv muscarinic actions:small dosev nicotinic actions:large dose1.muscarinic actions:small dose1.cardiovascular systemvvessel dilate a.NO release(M3 R EDRF(NO)GC cGMP intracellular Ca2+)b.
16、NA releasev BP (HR)v Heart depress:negative(chronotropic,dromotropic,inotropic)effect1.muscarinic actions:small dose2.glands 3.gastrointestinal tract:motility increase,secretion stimulation4.urinary bladder:detrusor muscle(逼尿肌)contraction,trigone and sphincter relaxation5.eye:sphincter muscle of iri
17、s(虹膜)contract:miosis ciliary muscle contract:near vision2.nicotinic actions:large dosevNN-R:dominant nerve actionsvNM-R:skeletal muscle contraction alkaloidsnPilocarpine(毛果芸香碱,匹鲁卡品)毛果芸香碱,匹鲁卡品)nMuscarine(毒蕈碱)毒蕈碱)n Arecoline(槟榔碱(槟榔碱)nOxotremorine(氧化震颤素)氧化震颤素)PilocarpinePharmacological actions:selectiv
18、ely activate M-R 1.Eye vmiosis:pupiliary sphincter vdecrease intraocular pressurevspasm of accommadation:ciliary muscle 2.Glands secrete increasingly (sweat gland,salivary gland)3.Smooth muscle4.Cardiovascular systemClinical uses 1.Glaucoma(青光眼)vangle-closure glaucomavopen-angle glaucoma What is Gla
19、ucoma?nincreased pressure within the eye.Cells inside the eye produce aqueous humor that maintains the shape of the eye and nourishes the tissues inside the eye.The balance of fluid production and drainage is responsible for maintaining normal pressure within the eye.nIn glaucoma,the drain becomes c
20、logged but the eye keeps producing fluid.Therefore,the pressure in the eye increases.The increased pressure in the eye actually can cause the eye to stretch and enlargeHow does Glaucoma affect the eye?nVision Loss.Pressure damage to the optic nerve and decreased blood flow to the retina,results in l
21、oss of vision.However,if the pressure in the eye remains uncontrolled,the retina degenerates and vision is permanently lost.Permanent blindness can occur within several hours if the pressure is very high and the glaucoma develops rapidlynPain.Humans have normal intraocular pressures between 10 and 2
22、0 mmHg.Glaucoma often results in pressures of 20-28 mmHg in humans.The pain persists in the form of a constant headache or migraine.This discomfort can result in decreased activity,less desire to play,irritability,or decreased appetite2.iritis(虹膜炎),iridocyclitis(虹膜睫状体炎)3.others:dry mouthAdverse reac
23、tions Muscarine(毒蕈碱)nAmanita muscaria (捕蝇蕈)Inocybe(丝盖伞菌属)Clitocybe(杯伞菌属)Section 2 N-R agonists nicotinenNicotine:from tobaccoAction:NM,NN,CNS and dependence (double phase)Tobacco poison:Hypertension,coronary heart disease,cerebrovascular disease,cancer,AtherosclerosisChina:Largest tobacco productive
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