神经阻滞镇痛术.ppt

Analgesics,Zhang,Bin,pain,a.Acutepain(sharppain)b.Chronicpain(dullpain),Paintransmissionpathway,Noxiousstimuli,Primaryafferentfibres,nociceptor,Spinalcord,Limbicsystem,Somato-sensorycortex,moodeffect,theaffectiveaspectofpain,thesensoryaspectofpain,Dorsalhorn,Drugtreatmentofpain,cholinoceptor-blockingdrugs,vasodilatordrugs(eg.Nitroglycerin),Carbamazepine,Localanaesthetics,Cortex,Spinalcord,Dorsalhorn,PGs,K+、H,BK,5-HT,NSAIDs,Opioids,Sitesofactionofdifferentdrugs,opioidanalgesics(narcoticanalgesic,addictiveanalgesics),Opium(阿片)isthedriedexudateobtainedfromunripeseedpodsofthepoppyPapaversomniferum,containingmorphine,codeine,andotheralkaloidsubstances.,Opiate(阿片剂)meansthatasubstanceisextractedfromopiumorissimilarinstructuretonaturalsubstancespresentinopium.,Opioid(阿片样物质)isatermthatdesignatessubstancesthatarenotderivedfromopium.Itrefersparticularlytoopioidpeptides,i.e.endogenouscompoundsthatbindtoopioidreceptorsandmimictheeffectofmorphine-likecompounds.,Widelyuseterm,Opium,Theflowerofpapaver,Opium(阿片),Opiate(阿片剂),MorphineCodeinePapaverine(罂粟碱),structure-activityrelationship,海洛因,吗啡,纳洛酮,Opioid(阿片样物质),Endogenousopioidpeptides:,Enkephalins,Endorphins,Dynorphins,Orphanin,1992,1973,1962,1975,analgesicsiteislaminaeIIIofperiventricularandperiaqueductalgrayarea,putforward“receptors”foropiateanalgesicsinbrain,isolatedthefirst“endogenousopioidpeptide”andnamedenkephalin,Clonedopioidreceptors:,Researchhistory,Opioidreceptors,Gprotein-coupledreceptors,Opioidreceptors,supraspinalanalgesia,sedation,euphoria,dependence,respiratorydepression,miosis,spinalanalgesia,sedation,dysphoria(烦躁不安),hallucination,spinalanalgesia,sedation,euphoria,dependence,respiratorydepression,:,:,:,:,Spinalcord,Dorsalhorn,enkephalins,Ca2+,Ca2+,Presynapticterminal,Postsynapticneuron,enkephalins,Thecellularmechanisms,enkephalins,Presynapticterminal,Postsynapticneuron,Thecellularmechanisms,Morphine+receptors,OpenK+channel,CloseCa2+channel,抑制冲动传导,Ach,NA,Glu,5-HT,Prelease,presynaptic,postsynaptic,Excitability,Thecellularmechanisms,Thecellularmechanisms,Presynapticinhibition:activationofopioidreceptorsonpresynapticnerveterminals.CloseCa2+channel,decreaseCa2+input,andtherebyreducetransmitterrelease(Ach,NA,Glu,5-HT,P).Postsynapticinhibition:activationofpostsynapticopioidreceptors.OpenK+channelsonpostsynapticneurons,increaseK+output,andtherebycausehyperpolarizationandthusreducepostsynapticneuronalexcitability.,Descendingpaininhibitorypathways,Localinhibitoryinterneuroninspinalcord,Ascendingpaintransmissionpathways,Endogenousopioidpeptides,Pharmacologicalactions,CNSSmoothmuscles3.Cardiovascularsystem,1.CNSeffects:principaleffectsAnalgesiaSedation&euphoriaRespiratorydepressionCoughsuppressionOthers:miosis,nausea,hormone,(1)Analgesiainsensitive:musclespasmspain,deafferentationpainpartiallysensitive:nervepain,CNScompressioninjury,bonecancersensitive:myocardialinfarction,othertypesofcancersrelieveanxietyanddistress,toleranceofpain,1.CNS,灼性神经痛(causalgia)系指在明确的神经损伤后，与损伤神经支配范围相一致的区域内出现的以剧烈灼样疼痛主要症状，表现为痛觉异常、痛觉过敏、交感神经机能障碍、血流障碍、出汗异常、骨、肌肉萎缩，有时表现出水肿性改变的慢性顽固性疼痛综合征。,(2)Sedationandeuphoria,drowsinessandcloudingofmentation,sleepinducedandarousedeasily,Euphoria,asenseofcontentmentandwell-being,Sedation:,themainreasonfordrugabuse,Site:limbicsystemandlocusceruleus,respiratoryrate，tidalvolumethemostcommoncauseofdeathfromacutepoisoninginfluencedbystimulusMechanisms:thesensitivityofrespiratorycentertoincreasedCO2tension,(3)Respiratorydepression,(4)Coughsuppression,antitussiveeffectbyinhibitingcoughcenter,codeine,(5)OtherCNSeffects,Miosis:pinpointpupilsNauseaandvomiting:CTZmusculartension:限制胸廓活动,影响呼吸Hormone:LH,FSH,prolactin,GH,ADH,2.SmoothmusclesystemGastrointestinalsystemBiliarytractUrinarysystemgenitalsystem,(1)Gastrointestinaltract,delayspassage,secretionofdigestivegland,indigestion,centralinhibition,acallofnaturedefecationreflex,GITtone,GITmotility,absorptionofwater,biliarycolic,constrictbiliarysmoothmuscleconstrictOddissphincter,pressureinthebiliarytract,(2)Biliarytract,(3)Urinarytract,constrictureteralsmoothmusclebladdersphinctertone,urinaryretention,uterinetone,prolonglabor,(4)Genitaltract,orthostatichypotension,Mechanisms:releaseofhistaminevasomotorcenter,3.Cardiovascularsystem,(1),peripheralarterialandvenousdilatation,(2)intracranialpressure,secondarytorespiratorydepression,Clinicaluses,AnalgesiaCardiacasthmaAntidiarrheaAntitussiveCombinedanesthesia,Analgesiaterminalcancermyocardialinfarctionrenalandbiliarycolic(atropine)trauma,burn,operation,atregulartimeandquantity,Pulmonaryedema,dyspnea,Acuteleftventriculardysfunction,shortofbreath(respiratorycenter),CO2retention,anxietyanddistress,Alveolarhypoventilation,Cardiacasthmaandmorphinetherapy,2.Cardiacasthma,oxygenconsumption,(1)Mechanisms:peripheralarterialandvenousdilationpreloadandafterloadpulmonaryedemasedationanxietyanddistressoxygenconsumptionthesensitivityofrespiratorycentertoCO2shortnessofbreath,Cardiacasthma,Opioidanalgesicdrugs,Morphine(吗啡)Heroin(海洛因，二醋吗啡)Codeine(可待因)Pethidine(哌替啶)Methadone(美沙酮)Fentanyl(芬太尼)buprenorphine(丁丙诺啡)Tramadol(曲马多),Morphine,1803Serturnerisolatedapureactivealkalinesubstancefromopium.Heproposedthename“morphine”foritafterMorpheus.,absorption,excretion,distribution,freedrug,blood,liver,iv.,Bioavailability25-30%,metabolism,美施康定（硫酸吗啡缓释片）1.强效，作用持续12hr。主要用于晚期癌症患者第三阶梯止痛。2.抑制呼吸，可引起恶心、呕吐、便秘及排尿困难，长期应用可产生耐受性、身体依赖性和成瘾性。,Heroin(diamorphine),Semisyntheticsubstance,prodrugofmorphineMorelipidsolublethanmorphineMorerapidonset,德国拜尔公司heroin在德文中意为英雄万能药药品转变为毒品白粉,Codeine,higheroralefficacy2.lowerefficacythanmorphine3.useasantitussive,severedrycough.联邦止咳露：麻黄碱+可待因+氯苯那敏+氯化铵,注意事项,不宜用于痰多粘稠者。连续应用不宜2周，因久用可成瘾。7岁儿童禁用。,Pethidine(dolantin),WeakerpotencythanMorphine,noantitussiveactionMorerapidonsetandshorterduration(2-4h)thanmorphineMetabolite:normeperidineconvulsionLyticcocktail,Methadone,1.syntheticcompound,derabstinencesyndrome3.routinelyusedindetoxificationofmorphineaddicts,Fentanyl,1.moreanalgesicpotentcythanmorphine:2.rapidonsetandshortdurationofaction3.fentanyl,alfentanil,remifentanil:adjunctivedrugforgeneralanaesthesia4.Fentanyl+Droperidol(氟哌利多):neuroleptanalgesia(神经阻滞镇痛术),Usedforminorsurgery,5.breakthroughcancerpain:,口腔经粘膜芬太尼拘橼酸盐(OralTransmucosalFentanylCitrate,OTFC),Fentanyllollipop,ACTIQ,芬太尼口腔粘膜贴片(Fentanylsublingualtablets),ABSTRAL,芬太尼透皮贴剂(Fentanyltransdermalsystem),多瑞吉,highlipid-soluble,Pentazocine,agonist,partialagonist,increasebloodpressureandcausetachycardia(NA),weakactionon:littleaddictiveliabilityprecipitatewithdrawalsyndromeofmorphineabuser,列入非麻醉药品。但久用仍会成瘾！,analgesiaandrespiratorydepression:weaker,Tramadol,Atypicalopioid:weakactivation,alsointeractswithmonoaminergicsystems(inhibitNAand5-HTreuptake)Alternativetotraditionalopioidanalgesics,2008年1月1日国家将曲马多列为精神药品进行管理,延胡索乙素和罗通定,罗通定为左旋体的延胡索乙素，是有效部分。镇静安定镇痛和中枢性肌肉松弛作用解热镇痛抗炎药镇痛作用哌替啶，镇痛作用与阿片受体及前列腺素均无关无明显成瘾性口服后10-30min起效，维持2-5h，对慢性持续性钝痛效果好不影响产程,1.Tolerance,Adverseeffects,largedosesatshortintervalsreadilycrosstolerancefullagonist:moreobvious,2.Dependence,physicaldependence：withdrawalsyndromepsychologicaldenpendence:compulsivedrug-seekingbehavior,Adverseeffects,身体依赖性,精神依赖性,渴求,戒断综合征,强迫性用药,依赖性,药物滥用,药物滥用（drugabuse）:非医疗目的反复使用具有依赖性潜能的精神活性物质。体验该物质产生的特殊精神效应。,药物误用(drugmisuse)：用药适应证选择不当/用量过大、疗程过长等错误用药行为。,WithdrawalsyndromeofOpioid,3.Generaladverseeffects,4.AcuteMorphinePoisoning,Naloxone,petitivefullantagonistforopioidR()2.opioidoverdose:reversescomaandrespiratorydepression3.differentialdiagnosisinmorphineabuser:precipitateswithdrawalsymptom4.shortt1/2(1h),repeatedinjections,Contraindications,obstetriclabor,breastingperiodobstructiveairwaydisea