胆碱受体阻断药

CholinoceptorBlockingDrugs成都大学医护学院药理教研室王跃锜原创1MuscarinicCholinoceptorBlockingDrugs毒蕈碱型受体阻断药，M受体阻断药2NicotinicCholinoceptorBlockingDrugs烟碱型受体阻断药，N受体阻断药ReceptorTypeOtherNamesLocation部位M1Nerves神经M2CardiacM2Heart,nerves,smoothmuscle心脏，神经，平滑肌M3Glands,smoothmuscle,endothelium腺体，平滑肌，内皮细胞M4CNS中枢神经系统M5CNSNMMuscletype,endplatereceptor肌肉型，终板受体Skeletalmuscleneuromuscularjunction骨骼肌神经肌肉接头NNNeuronaltype,ganglionreceptor神经元型，神经节受体postganglioniccellbody,dendrites突触后细胞，树突tertiaryaminealkaloidestersoftropicacid莨菪酸的叔胺生物碱酯Propantheline丙胺太林,普鲁本辛Quaternaryamineantimuscarinicagents季胺类化合物Mosttertiaryantimuscarinicdrugs（叔胺类抗胆碱药）arewellabsorbedfromthegut（消化道）andconjunctivalmembranes（结膜）.Incontrast,only10–30%ofadoseofaquaternaryantimuscarinicdrug（季胺类抗胆碱药）isabsorbedafteroraladministration（口服）,reflectingthedecreasedlipidsolubilityofthechargedmolecule（带电荷的分子）.Atropineandtheothertertiaryagents(叔胺类抗胆碱药)arewidelydistributedinthebody.SignificantlevelsareachievedintheCNS(中枢神经系统)within30minutesto1hour,andthiscanlimitthedosetoleratedwhenthedrugistakenforitsperipheraleffects.Scopolamine（东莨菪碱）israpidlyandfullydistributedintotheCNSwhereithasgreatereffectsthanmostotherantimuscarinicdrugs.Incontrast,thequaternaryderivatives（季胺类抗胆碱药）arepoorlytakenupbythebrainandthereforearerelativelyfree—atlowdoses—ofCNSeffects.Afteradministration,theelimination消除ofatropinefromthebloodoccursinapproximately15hours.About50%ofthedoseisexcretedunchangedintheurine尿.Mostoftherestappearsintheurineashydrolysis水解andconjugationproducts结合物.Thedrug‘seffectonparasympathetic副交感functiondeclinesrapidlyinallorgansexcepttheeye.Effectsontheiris瞳孔andciliarymuscle睫状肌persistformorethan72hours.Atropinecausesreversible(surmountable可逆的)blockadeatmuscarinicreceptors;thatis,blockadebyasmalldoseofatropinecanbeovercomebyalargerconcentrationofacetylcholine乙酰胆碱orequivalentmuscarinicagonistM受体阻断药.Tissues组织mostsensitivetoatropinearethesalivary唾液腺,bronchial支气管,andsweatglands汗腺.Secretionofacidbythegastricparietalcells胃壁细胞istheleastsensitive.Atropineishighlyselective选择性formuscarinicreceptorsM型受体.Itspotency效力atnicotinicreceptorsN型受体ismuchlower.Atropinedoesnotdistinguish区分amongtheM1,M2,andM3subgroups亚型ofmuscarinicreceptors.Incontrast,otherantimuscarinicdrugsaremoderatelyselectiveforoneoranotherofthesesubgroups.CentralNervousSystem中枢神经系统Inthedosesusuallyused,atropine阿托品hasminimalstimulanteffects兴奋效应ontheCNS,andaslower,longer-lastingsedative镇静effectonthebrain.Scopolamine东莨菪碱hasmoremarkedcentraleffects,producingdrowsiness嗜睡whengiveninrecommendeddosagesandamnesia失忆insensitiveindividuals.Intoxicdoses中毒剂量,scopolamine,andtoalesserdegreeatropine,cancauseexcitement兴奋,agitation焦躁,hallucinations幻觉,andcoma昏迷.Eye眼前房角变窄睫状肌松弛扩瞳畏光，调节麻痹房水回流受阻泪腺分泌减少，眼干涩CardiovascularSystem心血管系统心率上升，房室传导加快RespiratorySystem呼吸系统支气管分泌减少，支气管扩张GastrointestinalTract消化道Blockadeofmuscarinicreceptorshasdramaticeffectsonmotility运动andsomeofthesecretory分泌functionsofthegut肠道.AntimuscarinicdrugsM型抗胆碱药havemarkedeffectsonsalivarysecretion唾液分泌;drymouthoccursfrequentlyinpatientstakingantimuscarinicdrugs.Gastricsecretion胃酸分泌isblockedlesseffectively.Gastrointestinalsmoothmusclemotility胃肠平滑肌运动isaffectedfromthestomach胃tothecolon结肠.Ingeneral,thewallsoftheviscera内脏arerelaxed,andbothtone张力andpropulsivemovements蠕动arediminished.Therefore,gastricemptyingtime胃排空时间isprolonged,andintestinaltransittimeislengthened.GenitourinaryTract泌尿道Theantimuscarinicactionofatropineanditsanalogs同类药relaxessmoothmuscleoftheureters输尿管andbladderwall膀胱壁andslowsvoiding排尿.SweatGlands汗腺体温上升，皮肤血流增加散热降低皮肤变干汗液减少OphthalmologicDisorders眼科Accuratemeasurementofrefractiveerror屈光不正inuncooperativepatients,eg,youngchildren,requiresciliaryparalysis睫状肌麻痹.Also,ophthalmoscopicexamination眼底镜检查oftheretina视网膜isgreatlyfacilitatedbymydriasis散瞳.Therefore,antimuscarinicagents,administeredtopicallyaseyedrops眼药水orointment眼膏,areveryhelpfulindoingacompleteexamination.Foradultsandolderchildren,theshorter-actingdrugsarepreferred（如后马托品，托吡卡胺）.Foryoungerchildren,thegreaterefficacyofatropineissometimesnecessary.Asecondophthalmologicuseistopreventsynechia(adhesion粘连)formationinuveitis葡萄膜炎andiritis虹膜炎.DrugDurationofEffect(days)作用持续时间UsualConcentration(%)常用浓度Atropine阿托品7–100.5–1Scopolamine东莨菪碱3–70.25Homatropine后马托品1–32–5Tropicamide托吡卡胺0.250.5–1RespiratoryDisorders呼吸系统Theuseofatropine阿托品becamepartofroutinepreoperativemedication术前给药whenanesthetics麻醉suchasether乙醚wereused,becausetheseirritant刺激性anestheticsmarkedlyincreasedairwaysecretions分泌andwereassociatedwithfrequentepisodesoflaryngospasm喉痉挛.Preanesthetic麻醉前injectionofatropine阿托品orscopolamine东莨菪碱couldpreventthesehazardouseffects.CardiovascularDisorders心血管系统Markedreflexvagaldischarge迷走神经反射性兴奋sometimesaccompaniesthepainofmyocardialinfarction心肌梗塞(eg,vasovagalattack血管迷走神经性发作)andmayimpaircardiacoutput心输出.Parenteral注射atropineorasimilarantimuscarinicdrugisappropriatetherapyinthissituation.Rareindividualswithoutotherdetectablecardiacdiseasehavehyperactivecarotidsinusreflexes颈动脉窦反射andmayexperiencefaintness眩晕orevensyncope昏厥asaresultofvagaldischarge迷走兴奋inresponsetopressureontheneck,