药理4

1Chapter8CholinoceptorblockingdrugsAmericanorigin,containsAtropineCaoYongxiao曹永孝[e-mail];029-82655140•preganglionicfibers•parasympatheticfibers•afewsympatheticpostganglionicfibers•nervousfiberscontrollingadrenalmedulla.•somaticmotorfibers西安交大医学院药理学系曹永孝[e-mail];029-82655140西安交大医学院药理学系曹永孝[e-mail];029-82655140CholinoceptorantagonistsaredividedintoMandNsubgroupsbasedontheirspecificreceptoraffinities.TheNreceptorantagonistsconsistofganglion-blockers(N1,NN)andneuromuscularjunctionblockers(N2,NM).BasicPharmacologyoftheMReceptor-blockingDrugsarecalledparasympatholyticbecausetheyblocktheeffectsofparasympatheticautonomicdischarge.Naturallyoccurringcompoundswithanti-Mreceptoreffectshavebeenusedformillenniaasmedicines,poisons,andcosmetics.Atropineistheirprototype.Manysimilarplantalkaloidsareknown.Hundredofsyntheticanti-Mreceptorcompoundshavebeenprepared.西安交大医学院药理学系曹永孝[e-mail];029-82655140PharmacokineticsMostofantimuscarinicdrugsbeingtertiaryagentsreachestheCNSScopolamineisrapidlyandfullydistributedintotheCNSwellabsorbedfromthegutandwidelydistributedinthebodylimitthedosetoleratedwhereithasgreatereffectsthanmostothersThequaternaryderivativesarepoorlytakenupbythebrain.TheyarerelativelylesseffectofCNS西安交大医学院药理学系曹永孝[e-mail];029-82655140PharmacokineticsAtropinedisappearsrapidlyfromtheblood,t½of2h.Theeffectdeclinesrapidlyinallorgansexcepttheeye.Effectsontheeyepersistfor≥3days.About60%ofthedoseisexcretedunchangedintheurine.Therestappearsashydrolysisandconjugationproducts.西安交大医学院药理学系曹永孝[e-mail];029-82655140A.MechanismofAction:blocksMreceptorreversiblelyTheeffectivenessvarieswithtissues.Themostsensitivetissuestoatropinearethesalivary,sweatglands,digestivetract,bladder,bronchial,anduterus.Theleastsensitiveisthegastricparietalcellssecretingacid.AntimuscarinicagentsblockexogenousMreceptoragonistsmoreeffectivelythanendogenousACh.西安交大医学院药理学系曹永孝[e-mail];029-82655140PharmacodynamicsB.OrganSystemEffectsScopolaminehasmarkedcentraleffects,producingdrowsinessandamnesia.Intoxicdosescancauseexcitement,agitation,hallucinations,andcoma.1.CentralNerveSystemAtropinehasminimaleffectsontheCNS.西安交大医学院药理学系曹永孝[e-mail];029-826551402.Eye—BlockMreceptorMydriasis扩瞳西安交大医学院药理学系曹永孝[e-mail];029-82655140Thepupillaryconstrictormuscle,irisdependsonMreceptor.Atropineandotheranti-MdrugsblockMreceptorandresultsindilatationofirisandmydriasis.ThesmoothmusclesoftheirisThesphinctermuscleisinnervatedbycholinergicfiberstoMreceptors.Itscontractionundertheinfluenceofanagonistresultsinmiosis,anditsblockadebyatropineresultsinmydriasis.Theradialmuscleisinnervatedbyadrenergicfiberstoanalpha-1receptor.Itscontractionbyanagonistresultsinmydriasisanditsblockaderesultsinmiosis2.Eye—Mydriasis扩瞳西安交大医学院药理学系曹永孝[e-mail];029-826551402.Eye—BlockMreceptorMydriasis扩瞳intraocularpressure↑升眼压西安交大医学院药理学系曹永孝[e-mail];029-82655140AtropineblockMreceptor,contracttheiris,andreducetheanglespaceofanteriorchambersoastopreventoutflowofaqueoushumor,increasingthetheintraocularpressure.AtropineblocksMreceptor,inhibitsthecontractionoftheiris,andnarrowtheanglespaceofanteriorchambersoastopreventoutflowofaqueoushumor,increasingtheintraocularpressure.2.Eye—Mydriasis扩瞳intraocularpressure↑升眼压cycloplegia调节麻痹西安交大医学院药理学系曹永孝[e-mail];029-82655140Anti-MdrugsblockMreceptor,inhibitthecontractionoftheciliarymuscle,resultincycloplegia.Diagramofeyedepictingmajorpathwayforoutflowofaqueoushumor(heavyarrow)whichdrainsatSchlemm'scanal.Iftheanglebetweentheirisandthecorneaisnarrow,aphysicalimpedimentmayexisttodrainageandtheintraocularpressureisincreases.Thisisexacerbatedduringmydriasisbecausetheiriscontractstowardthatangle(narrowangleglaucoma)tofurtherimpedeoutflow.Theciliarymuscleisasphincter.Whencontracting,itrelaxesthesuspensoryligamentsonthelens.Thelensroundsofitsownelasticitytoaccomodatetonearvision.UndertheinfluenceofexcessACh,however,themusclegoesintociliospasm,andcannotreaccomodateforfarvision.Thisoccursinanticholinesterasepoisoning.2.Eye—Mydriasis扩瞳intraocularpressure↑升眼压cycloplegia调节麻痹Anti-MdrugsblockMreceptor,inhibitthecontractionoftheciliarymuscle,resultincycloplegia.Antimuscarinicdrugsreducelacrimalsecretion.西安交大医学院药理学系曹永孝[e-mail];029-826551403.CardioavascularsystemCardiomuscleiscontrolledbylesserdegreeofMreceptor.Atropinehasnoclinicalsignificanteffectonit.西安交大医学院药理学系曹永孝SinoatrialnodeiscontrolledbyMreceptor.AtropineblocksMreceptorandcausestachycardia.LowerdosesresultsininitialbradycardiaduetoblockpresynapticMreceptorwhichlimitAChrelease.AtropineblocksMreceptoronatrioventricularnode,increasetheconduction,andthePRintervalofECG.Intoxicdoses,atropineblocksintraventricularconductionTheskeletalmusclevascularbedcontainsMreceptor.AlmostallvesselscontainendothelialMreceptorsthatmediatevasodilation.Thereceptorsarereadilyblockedbyantimuscarinicdrugs.Attoxicdoses,andinsomeindividualsatnormaldoses,atropinecausecutaneousvasodilation.Butthereislittleeffectonbloodp