【文档说明】阿托品atropine药理学英文课件.ppt，共(125)页，2.301 MB，由小橙橙上传

转载请保留链接：https://www.ichengzhen.cn/view-233908.html

以下为本文档部分文字说明：

阿托品atropine——药理学英文课件Chapter5IntrductiontoPharmacologyofEfferentNervousSystemZhangBinInstituteofPharmacologyScho

olofMedicineShandongUniversityOrganizationofNervoussystemefferentnervoussystem(ENS)◼autonomicnervoussystem(vegetativenervoussystem)◼somaticmotorn

ervoussystemEfferentneuronsoftheautonomicnervoussystemClassificationofENSaccordingtothereleasedneurotr

ansmitters❖cholinergicnerve:acetylcholine(Ach)❖noradrenergicnerve:noradrenaline(NA)ClassificationofENSParasympatheticnerveCentralnervoussystemA

chskeletalmuscleAchNAAchAchsweatglandsAchAchAchadrenalmedullasomaticmotornervesympatheticnerveglands,smoothmu

scle,heartheart,vessel,smoothmuscleSection1NeurotransmitterandReceptorofENS◼NeurotransmitterofENS◼ThereceptorsofENS一.NeurotransmitterofENS1.Deve

lopmentofneurotransmittertheory◼100yearsagoChemicaltransmissionelectronictransmission◼1946VonEulerNA(norad

renaline)◼1921loewidoublefrogheartexperiment◼1926DaleAch(acetylcholine)2.Biosynthesis,storage,releaseandtermina

tionofneurotransmitters◼Ach(acetylcholine)◼NA(noradrenaline)inhibitor2.Biosynthesis,storage,releaseandterminationofneurotransmitters(1)

Biosynthesis◼choline+acetylcoenzymeAAch◼tyrosinedopaDANAcholineacetylaseTHDDDH(2)Storage+ATP+proteinstorei

nvesiclesAchNA(3)release◼exocytosis◼quantalrealease◼cotransmission(4)Termination❖Ach:acetylcholinesterase

(AchE)insynapse❖NA:uptake1(neuronaluptake)75%-90%storageinvesicles\MAOuptake2(non-neuronaluptake)COMT\MAO二.ThereceptorsofENSClass

ification,DistributionandEffectCholinereceptors(Cholinoceptors)◼M-R:muscarine◼N-R:nicotineCholinoceptorsM-R:❖M1-R:ganglion,CNS❖M2-

R:heart,presynapticsites(negativefeedback),CNS❖M3-R:exocrineglands,smoothmuscle,endothelium,CNS❖M4–R:exocrineglands,smoothmuscle,C

NS❖M5-R:CNSCholinoceptorsN-R:nicotineNM-R:skeletalmuscleNN-R:ganglionandCNSadrenoceptor:NAADα-R◼α1-R:postsynapticeffectorcells(especial

lysmoothmuscle)◼α2-R:presynapticnerveterminals(negativefeedback),platelet,smoothmuscle,lipocytesadrenoceptor

β-R❖β1-R:postsynapticeffectorcells,(especiallyheart,lipocytes,)presynapticnerveterminals❖β2-R:postsynapticeffectorcells,(especiallysmoothmu

scle)❖β3-R:postsynapticeffectorcells,(especiallylipocytes)Classificationofreceptoraccordingtotheirstructure◼G-protein-couple

dreceptor:-R,-R,M-R,DA-R,5-HT-R◼Ligand-gatedreceptorsN-RStructureofG-protein-coupledReceptorMolecularMechanismofGq-protein-c

oupledReceptorMolecularMechanismofGi/s-protein-coupledReceptorStructureofligand-gatedionchannelReceptorMolecularM

echanismofligand-gatedionchannelreceptor◼1.CholinoceptorsM-R:G-protein-coupledreceptorM1-R:Gq-protein-coupledreceptorM2-R-Gi-protein-couple

dreceptorN-R:ligand-gatedionchannelreceptor◼2.adrenoceptor:G-protein-coupledreceptorα1–R:Gq-protein-coupledreceptorα2–R:Gi-protein-coupledreceptorβ

-R:Gs-protein-coupledreceptorMolecularMechanismofReceptorN-RNa+,K+,Ca2+G-protein-coupledreceptorligand-gatedreceptor:(-)PKAcAMPM1-R

M2-RGqGiK+,Ca2+(-)ACcAMPPLCIP3DAGα1-Rα2-Rβ-R(+)AC(-)ACGiGqPLC,PLA2,PLDGscAMP(-)PKA(+)PKACa2+(+)PKCterminology◼adrenergic◼adrenergicre

ceptor◼cholinergic◼cholinergicreceptor◼postsynapticreceptor◼presynapticreceptorSection2ThephysiologicalactionsofENS◼Co-innervationandDomin

antTheory◼Sympatheticactions:fightandflightresponse◼Parasympatheticactions:restanddigestresponseSection3ThebasicmechanismsofactionsofENSdrugs◼1.

Directactionofreceptorsagonistblocker(antagonist)◼2.lnfluenceofneurotransmittersbiosynthesisreleasestorageconv

ersionSection4TheclassificationoftheENSdrugs（三）抗胆碱酯酶药Chapter6parasympathomimetics◼Cholinoceptoragonists(ch

olinomimetics)◼Anticholinesteraseagents(cholinesterase-inhibitingdrugs)◼DrugsofenhancersofAChreleaseCholinoceptorAgonists➢M-Ragonists:Cholineester

s:acetylcholine(ACh)alkaloids:pilocarpine◼N-Ragonists:nicotineSection1M-RagonistsAcetylcholine(ACh)1.unstable2.l

owselectivity3.administrationroute[Pharmacologicalactions]DirectlyactivateM-R,N-R❖muscarinicactions:smalldose❖nicotinicactions:largedose

1.muscarinicactions:smalldose1.cardiovascularsystem◼vesseldilatea.NOrelease↑(M3R→EDRF(NO)↑→GC→cGMP↑→intracellularCa2+↓)b.NArelease↓◼BP(HR)◼Heartdepr

ess:negative(chronotropic,dromotropic,inotropic)effect1.muscarinicactions:smalldose2.glands↑3.gastrointestinaltract

:motilityincrease,secretionstimulation4.urinarybladder:detrusormuscle(逼尿肌）contraction,trigoneandsphincterrelaxat

ion5.eye:sphinctermuscleofiris(虹膜）contract:miosisciliarymusclecontract:nearvision2.nicotinicactions:largedose❖NN-R:dominant

nerveactions❖NM-R:skeletalmusclecontractionalkaloids◼Pilocarpine（毛果芸香碱，匹鲁卡品）◼Muscarine（毒蕈碱）◼Arecoline（槟榔碱）◼Oxotremorine（氧化震颤素）PilocarpinePha

rmacologicalactions:selectivelyactivateM-R1.Eye◼miosis:pupiliarysphincter❖decreaseintraocularpressure❖spasmofaccommadation:ciliarymuscle

2.Glandssecreteincreasingly(sweatgland,salivarygland)3.Smoothmuscle4.CardiovascularsystemClinicaluses1.Glaucoma(青光眼）◼angle-closuregla

ucoma❖open-angleglaucomaWhatisGlaucoma?◼increasedpressurewithintheeye.Cellsinsidetheeyeproduceaqueoushumo

rthatmaintainstheshapeoftheeyeandnourishesthetissuesinsidetheeye.Thebalanceoffluidproductionanddrainageisresponsibleformaintaini

ngnormalpressurewithintheeye.◼Inglaucoma,thedrainbecomescloggedbuttheeyekeepsproducingfluid.Therefore,thepre

ssureintheeyeincreases.TheincreasedpressureintheeyeactuallycancausetheeyetostretchandenlargeHowdoesGlaucomaaffecttheeye?◼VisionLoss.Pressuredamagetot

heopticnerveanddecreasedbloodflowtotheretina,resultsinlossofvision.However,ifthepressureintheeyeremainsuncontrolled,theretinadegeneratesandvi

sionispermanentlylost.Permanentblindnesscanoccurwithinseveralhoursifthepressureisveryhighandtheglaucomadevelopsrapidly◼Pain.Human

shavenormalintraocularpressuresbetween10and20mmHg.Glaucomaoftenresultsinpressuresof20-28mmHginhumans.Thepainp

ersistsintheformofaconstantheadacheormigraine.Thisdiscomfortcanresultindecreasedactivity,lessdesiretoplay

,irritability,ordecreasedappetite2.iritis（虹膜炎），iridocyclitis（虹膜睫状体炎）3.others:drymouthAdversereactionsMuscarine（

毒蕈碱）◼Amanitamuscaria（捕蝇蕈）Inocybe（丝盖伞菌属）Clitocybe（杯伞菌属）Section2N-Ragonists——nicotine◼Nicotine:fromtobaccoAction:NM,NN,

CNSanddependence(doublephase)Tobaccopoison:Hypertension,coronaryheartdisease,cerebrovasculardisease,cancer,Atherosclerosis

China:Largesttobaccoproductivecountry,LargesttobaccoconsumptioncountryNosmoking！Stopsmoking！Section3Anticholinestera

seAgentsCholinesterase:trueCholinesterase(AChE)PseudocholinesteraseAnticholinesteraseAgents-----indirectactingcholinomimeticsClassi

ficationaccordingtostructure◼non-covalentbondingagents:Edrophoniumchloride(依酚氯铵):strongpolarity,shorttacrine(他克林)

:stronglipophilia,longdonepezil(多奈哌齐):stronglipophilia,long◼Carboxamide(氨甲酰类):Physostigmine(毒扁豆碱)Pyridostigmin

e(吡斯的明)Demecarium(地美溴铵)rivastigmine(利凡斯的明)◼orgnaophosphoruscompound(有机磷化合物)亲和力亲脂性BBB维持时间依酚氯铵一般弱—短他克林较高强＋长多奈哌齐较高强＋长Classificationaccordingt

opharmacologicalproperty❖ReversibleAnticholinesteraseagents❖irreversibleAnticholinesteraseagents❖Mechanismsofactions:❖Pharmacologica

lactions:1.eye2.gastrointestinaltract（esophagus,stomach,intestine)3.motorendplate4.glands5.cardiovascularsystemClinicalUses1.My

astheniagravis(重症肌无力):NeostigminePyridostigmine(吡斯的明)Ambenoniumchloride(安贝氯胺)ClinicalUses2.Postoperativeabdominaldist

ension;Urinaryretention:Neostigmine3.glaucoma:Physostigmine(毒扁豆碱)Demecarium(地美溴铵)4.intoxicationofd-tubocurarine:Neostigm

ine，Edrophoniumchloride(依酚氯铵):5.Alzheimer’sdisease:tacrine,donepezil,rivastigmine,galanthamin6.Supraventr

iculartachyarrhythmiasCommonusedagentsReversibleAnticholinesteraseagentsNeostigmine(新斯的明）❖actions：1.InhibitAChE2.ActivateNM-Ronmotorendplate3.Stronge

ffectonskeletalmuscle4.NotintoCNS❖Uses:1.Myastheniagravis:Skeletalmusclecontractionpo,sc,imiv2.Postoperativeabdomin

aldistension;Urinaryretention3.intoxicationofd-tubocurarineandatropine4.Supraventriculartachyarrhythmias5.G

laucomaAdversereactions:◼Cholinergicoverexcitation(cholinergiccrisis)Treatment:atropined-tubocurarinePyridostigmine(吡斯的明)

◼WeakerthanNeostigmine◼slowerthanNeostigmine◼LongerthanNeostigmine◼NotintoCNS◼UsedtotreatMyastheniagra

vis◼Contraindication:mechanicalileus，urinaryobstructionPhysostigmine◼characteristics1.Strongerthanneostigmine2.CanenterCNS3.HavenodirectactiononR◼act

ions：1.eye2.systemicaction◼Uses:1.Glaucoma2.Intoxicationofanticholineagents:AtropineTricyclicantidepressantDibenzothiazineantipsychotics◼Compa

risontopilocarpine1.Morerapid2.Stronger3.longer◼Donepezil◼Rivastigmine◼Tacrine——Alzheimer’sdiseaseReversibleanticholinesteraseagent

s❖neostigmine\Pyridostigmine\Ambenonium\Galanthamine:Myastheniagravis❖Physostigmine\Demecarium:Glaucoma❖Edrophoniumch

loride:diagnostictestformyastheniagravis❖Donepezil\rivastigmine\Tacrine\:Alzheimer’sdiseaseIrreversibl

eAnticholinesteraseAgents--Organophosphates❖Mechanismsofintoxication❖Pathwayofintoxication❖signsofacuteintoxication1.Mmanifestation(muscar

inicexcess)2.Nmanifestation(nicotiniceffects)3.CNSeffects❖ChronicintoxicationPreventionandtreatmentoforganophosphatesinto

xication❖Prevention❖Treatmentofacuteintoxication1.maintenanceofvitalsigns2.Decontaminationtopreventfurtherabsorption3.Symptomatictreat

ment1)atropine2)cholinesterasereactivatorCholinesteraseReactivatorsPralidoximeiodide(PAM):碘解磷定➢Mechanismsofaction➢therap

euticeffect1.inhibitNmmanifestation——strong2.inhibitMmanifestation——weak3.CNS碘解磷定磷酰化AChE复合物磷酰化碘解磷定AChEPralidoximechloride(PAM-Cl

):氯解磷定betterwater-solubilityimandivlittleadversereactionChapter7cholinoceptor-blockingdrugs◼M-Rblockers◼N-Rblockers:NN

-RblockersNM-RblockersMuscariniccholinoceptor-blockingdrugs◼Atropineandatropine-likealkaloids◼Syntheticatropinesubstitutesatropine-likealk

aloidsandtheirresources植物主要生物碱颠茄(atropabelladonna)莨菪碱(hyoscyamine)曼陀罗(daturastramonium)莨菪碱洋金花(datruasp)东莨菪碱(

scopolamine)莨菪(hyoscyamusniger)莨菪碱唐古特莨菪(scopoliatangutica)山莨菪碱(anisodamine)◼樟柳碱(anisodine颠茄莨菪曼陀罗洋金花Atropine◼pharmacologicalactions:blo

ckM-RblockNN-Rinlargedosepharmacologicalactions1.glands:secretion↓salivary,sweat>lacrimal,respiratory>gastricacid,pancreatic,intesti

naljuice2.eyes(1)mydriasis(2)increaseintraocularpressure(3)paralysisofaccommodation3.splanchnicsmoothmuscle:relaxation(spasmodic)GI

tract,detrusormuscleofbladder:significantBiletract,bronchial,uterine(子宫):weak4.heart:(1)HRTherapeuticdose:decrease(presynapticM1block

ade)Largedose:increase(blockvagaleffectonM2–R)(2)A-Vconduction:5.vessels:dilation(inlargedose)(1)Direct

effect(2)Compensativereactionbytemperaturerise6.CNS:excitationOrgansensitivity:Gland＞eye＞splanchnicsmoothm

uscle＞cardiovascularsystem＞CNS.ClinicalUses1.Anti-smoothmusclespasm2.Pre-anaesthesiamedicationagent3.Ophthalmologicaluse(1)iri

docyclitis(2)optometry(3)examinationofretina4.Bradyarrhythmias5.Shock(septicshock):Cautions6.Intoxicationoforganophosphateadversereact

ions1.CommonSideEffects2.AcutePoisoningminimallethaldose:adults–80~130mgchildren--10mgPrevention1.Decon

tamination:topreventfurtherabsorption2.Antidotes:Parasympathomimetics3.Maintenanceofvitalsignscontraindicti

ons❖Glaucoma❖prostatichypertrophyanisodamine(654-2)山莨菪碱◼Characteristicofactions1.highselectivity(smoothmuscleand

vessels)2.littlesideeffect(notpassthroughBBB)◼Uses1.septicshock2.visceralcolics.Scopolamine(东莨菪碱)[Characteristics]1.CNSactio

ns:depression(strong)2.peripheralactions:glands:strongothers:weak❖Uses:1.preanaesthesiamedication2.preventionmotionsicknes

s3.Parkinsondisease4.traditionalmedicineanaesthesia中药麻醉◼华佗（公元141～203年）◼“麻沸散”◼曼陀罗(洋金花)◼徐州医学院附属医院:中药麻醉汤(针剂)◼东莨菪碱Section2Syntheticatropinesubstitutes◼Sy

ntheticMydriatics◼SyntheticAntispasmatics◼SelectiveM1AntagonistsSyntheticMydriatics◼Homatropine(后马托品)◼Tropicamide(托吡卡胺)◼Cyclopentolate(环

喷托酯)◼Eucatropine(尤卡托品)Comparisonofsomemydriaticsdrugsconcentration(%)mydriasisparalysisofaccommodationpeak

(m)duration(d)peak(h)duration(d)atropine1.030~407~101~37~12homatropine1.0~2.040~601~20.5~11~3tropicamide0.5~1.020~400.250.5<0.25cyclopentolate0.53

0~50110.25~1eucatropine2.0~5.0301/12~1/4◼Uses:iridocyclitisoptometryexaminationofretinaSyntheticAntispasmaticsQuaternaryamines(季胺类)：P

ropanthelinebromide(溴丙胺太林，普鲁本辛)1.selectiveblockadeofGItract:2.ulceration,GIspasm,bladderstimulation3.neuromuscularblockaction:toxicdose4.lo

wBBBpermeabilityQuaternaryamines(季胺类)：Ipratropiumbromide(异丙托溴胺)1.Relievebronchospasmbyinhalation2.Uses:chronicobstructivepulmon

arydisease,bronchialasthma3.ganglionicblockactionstrongerthanatropine4.lowBBBpermeabilityTertiaryamines(叔胺类)：Mydriat

icsAnticholinergicinCNSAntispasmaticagentsBenactyzine(贝那替嗪，胃复康）1.Relievesmoothmusclespasm2.AntianxietyeffectSelectiveM1Antagonists◼Pi

renzepine(哌仑西平)◼Telenzepine(替仑西平)◼Inhibitsecretionofgastricacid◼Clinicaluse:pepticulcer◼NotintoCNS受体亚型分布效应N1受体N2受体M1受体M2受体M3受体神经节肾上腺髓质骨骼肌神经节窦房节房室节心肌平

滑肌外分泌腺神经节除极儿茶酚胺释放骨骼肌收缩介导迟发性兴奋突触后电位延缓自发除极，减慢心率减慢传导速度降低收缩力收缩分泌增多受体亚型分布效应1受体2受体1受体2受体3受体血管平滑肌生殖道泌尿道平滑肌肝脏小肠平滑肌心脏胰岛细胞血管平滑

肌血小板神经末梢心脏肾小球旁器细胞平滑肌肝脏脂肪组织收缩收缩肝糖原分解松弛增强收缩力减少胰岛素分泌收缩聚集减少去甲肾上腺素释放兴奋增加肾素分泌松弛肝糖原分解脂肪分解