神经阻滞镇痛术课件

AnalgesicsZhang,Bin1-AnalgesicsZhang,Bin1-paina.Acutepain(sharppain)b.Chronicpain(dullpain)2-paina.Acutepain(sharppain)PaintransmissionpathwayNoxiousstimuliPGsK+、H+BK5-HTPrimaryafferentfibresnociceptorSpinalcordLimbicsystemSomato-sensorycortexmoodeffect,theaffectiveaspectofpainthesensoryaspectofpainDorsalhorn3-PaintransmissionpathwayNoxioseverepainOpioids(eg.Morphine)inflammatorypainNSAIDs(eg.Aspirin)localanaesthesia

smoothmusclecolicanginapectorisinducedbycoronaryarteryspasm

trigeminalpainDrugtreatmentofpaincholinoceptor-blockingdrugsvasodilatordrugs(eg.Nitroglycerin)

CarbamazepineLocalanaesthetics4-severepainOpioids(eg.MorphiCortexSpinalcordDorsalhornPGsK+、H＋BK5-HTNSAIDsOpioidsSitesofactionofdifferentdrugs5-CortexSpinalcordDorsalho

opioidanalgesics

(narcoticanalgesic,addictiveanalgesics)

6-opioidanalgesics

(narcotica

Opium(阿片)

isthedriedexudateobtainedfromunripeseedpodsofthepoppyPapaversomniferum,containingmorphine,codeine,andotheralkaloidsubstances.Opiate

(阿片剂)meansthatasubstanceisextractedfromopiumorissimilarinstructuretonaturalsubstancespresentinopium.Opioid

(阿片样物质)isatermthatdesignatessubstancesthatarenotderivedfromopium.Itrefersparticularlytoopioidpeptides,i.e.endogenouscompoundsthatbindtoopioidreceptorsandmimictheeffectofmorphine-likecompounds.Widelyuseterm7-Opium(阿片)isthedriedexudaOpium

TheflowerofpapaverOpium(阿片)8-OpiumTheflowerofpapaveOpiate(阿片剂)MorphineCodeinePapaverine(罂粟碱)

……9-Opiate(阿片剂)Morphine9-structure-activityrelationship海洛因吗啡纳洛酮OH10-structure-activityrelationshiOpioid(阿片样物质)Endogenousopioidpeptides:

Enkephalins

Endorphins

Dynorphins

Orphanin11-Opioid(阿片样物质)Endogenousopioi1992~197319621975

analgesicsiteislaminaeIIIofperiventricularandperiaqueductalgrayareaputforward“receptors”foropiateanalgesicsinbrainisolatedthefirst“endogenousopioidpeptide”andnamedenkephalinClonedopioidreceptors:μ

κ

δ

Researchhistory12-1992~197319621975analgesicsiExtracellularCytoplasmicNH2HOOCOpioidreceptorsGprotein-coupledreceptors

13-ExtracellularCytoplasmicNH2HOOOpioidreceptorssupraspinalanalgesia,

sedation,euphoria,dependence,respiratorydepression,miosisspinalanalgesia,sedationdysphoria(烦躁不安),hallucinationspinalanalgesia,sedation,euphoria,dependence,

respiratorydepression

:

:

::14-OpioidreceptorssupraspinalanSpinalcordDorsalhornenkephalinsCa2+Ca2+PresynapticterminalPostsynapticneuronenkephalins

Thecellularmechanisms15-SpinalcordDorsalhornenkeenkephalinsPresynapticterminalPostsynapticneuronThecellularmechanismsmorphine16-enkephalinsPresynapticterminMorphine+receptorsOpenK+channelCloseCa2+channel抑制冲动传导Ach,NA,Glu,5-HT,Prelease

presynapticpostsynapticExcitability

Thecellularmechanisms17-Morphine+receptorsOpenK+chThecellularmechanismsPresynapticinhibition:activationofopioidreceptorsonpresynapticnerveterminals.CloseCa2+channel,decreaseCa2+input,andtherebyreducetransmitterrelease(Ach,NA,Glu,5-HT,P).Postsynapticinhibition:activationofpostsynapticopioidreceptors.OpenK+channelsonpostsynapticneurons,increaseK+output,andtherebycausehyperpolarizationandthusreducepostsynapticneuronalexcitability.18-ThecellularmechanismsPresynaDescendingpaininhibitorypathwaysLocalinhibitoryinterneuroninspinalcordPainAscendingpaintransmissionpathwaysEndogenousopioidpeptides19-DescendingpaininhibitorypatPharmacologicalactionsCNSSmoothmuscles3.Cardiovascularsystem20-PharmacologicalactionsCNS21.CNSeffects:principaleffectsAnalgesiaSedation&euphoriaRespiratorydepressionCoughsuppressionOthers:miosis,nausea,hormone

21-1.CNSeffects:principaleffec(1)Analgesia

insensitive:musclespasmspain,deafferentationpainpartiallysensitive:nervepain,CNScompressioninjury,bonecancersensitive:myocardialinfarction,othertypesofcancersrelieveanxietyanddistress,toleranceofpain1.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。22-(1)Analgesia1.CNS灼性神经痛(caus(2)Sedationandeuphoria

drowsinessandcloudingofmentation

sleepinducedandarousedeasily

Euphoria

asenseofcontentmentandwell-being

Sedation:themainreasonfordrugabuseSite:limbicsystemandlocusceruleus23-(2)Sedationandeuphoria

respiratoryrate，tidalvolume

themostcommoncauseofdeathfromacutepoisoninginfluencedbystimulusMechanisms:

thesensitivityofrespiratorycentertoincreasedCO2tension

(3)Respiratorydepression24-respiratoryrate，tidalv(4)Cough

suppressionantitussiveeffectbyinhibitingcoughcentercodeine

(5)OtherCNSeffectsMiosis:

pinpointpupilsNauseaandvomiting:

CTZmusculartension:限制

胸廓活动,影响呼吸Hormone:

↓LH,FSH,

↑prolactin,GH,ADH25-(4)Coughsuppressionantituss2.Smoothmusclesystem

GastrointestinalsystemBiliarytractUrinarysystemgenitalsystem

26-2.Smoothmusclesystem26-(1)Gastrointestinaltract

delayspassage

secretionofdigestiveglandindigestioncentralinhibition

acallofnaturedefecationreflexGITtone

GITmotilityabsorptionofwaterconstipation27-(1)Gastrointestinaltractde

biliarycolic

constrictbiliarysmoothmuscleconstrictOddi'ssphincterpressureinthebiliarytract(2)Biliarytract28-biliarycolicconstrictbilia(3)Urinarytractconstrict

ureteralsmoothmusclebladdersphinctertoneurinaryretention

uterinetone

prolonglabor

(4)Genitaltract29-(3)Urinarytractconstricture

orthostatichypotensionMechanisms:

releaseofhistaminevasomotorcenter3.Cardiovascularsystem(1)peripheralarterialandvenousdilatation(2)intracranialpressuresecondarytorespiratorydepression30-orthostatichypotenClinicalusesAnalgesiaCardiacasthmaAntidiarrheaAntitussiveCombinedanesthesia31-ClinicalusesAnalgesia31-Analgesia

terminalcancermyocardialinfarctionrenalandbiliarycolic(atropine)trauma,burn,operationatregulartimeandquantity32-AnalgesiaatregulartimeandqPulmonaryedemadyspneaAcuteleftventriculardysfunctionshortofbreath(respiratorycenter)

CO2retentionanxietyanddistressAlveolarhypoventilationmorphineReducecardiacpreloadandafterloadReducethesensitivityoftherespiratorycentertoincreasedCO2SedationCardiacasthma

andmorphinetherapy

2.Cardiacasthmaoxygenconsumption

33-Pulmonaryedemadyspne(1)Mechanisms:①

peripheralarterialandvenousdilationpreloadandafterloadpulmonaryedema②

sedation

anxietyanddistress

oxygenconsumption

③

thesensitivityofrespiratorycenterto

CO2

shortnessofbreathCardiacasthma34-(1)Mechanisms:CardiacasthmaOpioidanalgesicdrugsMorphine(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)35-OpioidanalgesicdrugsMorphineMorphine1803Serturnerisolatedapureactivealkalinesubstancefromopium.Heproposedthename“morphine”foritafterMorpheus.36-Morphine1803SerturnerabsorptionexcretiondistributionfreedrugoralFirstpasseliminationsc.im.bloodliverplacentalfetuslittlecrosstheBBB,butenoughforitsfunctionmorphine-6-glucuronidekidney,

breastiv.Bioavailability25-30%metabolism37-absorptionexcretiondistributi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。38-美施康定（硫酸吗啡缓释片）38-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39-Heroin(diamorphine)SemisyntheCodeinehigher

oral

efficacy2.lowerefficacythanmorphine3.useasantitussive,severe

drycough.

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。40-Codeinehigheroralefficacy注意Pethidine(dolantin)WeakerpotencythanMorphine,noantitussiveactionMorerapidonsetandshorterduration(2-4h)thanmorphineMetabolite:normeperidine

convulsion

Lyticcocktail41-Pethidine(dolantin)WeakerpotMethadone

1.syntheticcompound,equalanalgesiatomorphine2.milderabstinencesyndrome3.routinelyusedindetoxification

ofmorphineaddicts42-Methadone1.syntheticcompoFentanyl1.moreanalgesicpotentcythanmorphine:2.

rapidonsetandshortdurationofaction3.

fentanyl,alfentanil,remifentanil:adjunctivedrugforgeneralanaesthesia

4.Fentanyl+

Droperidol(氟哌利多):

neuroleptanalgesia(神经阻滞镇痛术)Usedforminorsurgery5.breakthroughcancerpain:43-Fentanyl1.moreanalgesicpot口腔经粘膜芬太尼拘橼酸盐

(OralTransmucosalFentanylCitrate,OTFC)FentanyllollipopACTIQ

芬太尼口腔粘膜贴片

(Fentanylsublingualtablets)ABSTRAL

芬太尼透皮贴剂

(Fentanyltransdermalsystem)多瑞吉

highlipid-soluble44-口腔经粘膜芬太尼拘橼酸盐

(OralTransmucosaPentazocineκ,

agonist,μpartialagonist

increasebloodpressureandcausetachycardia(

NA)weakactiononμ:

littleaddictiveliabilityprecipitatewithdrawalsyndromeofmorphineabuser列入非麻醉药品。但久用仍会成瘾！analgesiaandrespiratorydepression:weaker45-Pentazocineκ,agonist,μpaTramadolAtypicalopioid:weakμ

activation,alsointeractswithmonoaminergicsystems(inhibitNAand5-HTreuptake)Alternativetotraditionalopioidanalgesics2008年1月1日国家将曲马多列为精神药品进行管理46-TramadolAtypicalopioid:weak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47-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。41.ToleranceAdverseeffects

largedosesatshortintervalsreadilycrosstolerancefullagonist:moreobvious48-1.ToleranceAdverseeffects48-2.Dependence

physicaldependence：withdrawalsyndrome

psychologicaldenpendence:

compulsivedrug-seekingbehaviorAdverseeffects49-2.Dependencephysicaldepend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50-身体依赖性精神依赖性渴求戒断综合征强迫性药物滥用（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。51-药物滥用（drugabuse）:非医疗目的反复使用具有依

rhinorrheaLacrimation

chills

gooseflesh(piloerection)yawningsweatingmuscularachevomitingdiarrhea

anxiety

hostilityhyperventilation

Withdrawal

syndromeofOpioid52-rhinorrheaLacrimation3.Generaladverseeffects1Constipation5Respiratorydepression2Biliarycolic6Posturalhypotension3Nauseaandvomiting7Increasedintracranialpressure4Urinaryretention8Dysphoria53-3.Generaladverseeffects1

Clinicaloverdose

Accidentalpoisoninginaddicts

30mg

–toxicthreshold120mg–lethalthresholdPinpointpupilsDeeprespiratorydepressionComaTreatments:

EstablishpatentairwayAdequateventilation

Naloxone

iv.Thetriad：4.AcuteMorphinePoisoning54-ClinicaloverdoseTreatments:TNaloxone1.competitivefullantagonistforopioidR(μ)2.opioidoverdose:reversescomaandrespiratorydepression3.differentialdiagnosisinmorphineabuser:precipitateswithdrawalsymptom4.shortt1/