腫瘤內(nèi)科的疼痛管理課件

腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理現(xiàn)狀和對策腫瘤內(nèi)科的疼痛管理癌癥相關疼痛的全球性Cancer-relatedpainisamajorissueofhealthcaresystemsworldwide.Thereportedincidence,consideringallstagesofthedisease,is51%,whichcanincreaseto90%intheadvancedandterminalstages.Foradvancedcancer,painismoderatetosevereinabout40–50%andverysevereorexcruciatingin25–30%ofcases.

腫瘤內(nèi)科的疼痛管理疼痛治療的現(xiàn)狀在歐洲ArecentEuropeanstudythatfocusedontheprevalenceandtreatmentofcancerpainhasbeenperformedin11EuropeancountriesandIsraelin2006–2007.Atotalof5,084cancerpatientswerecontactedand56%(573)ofthemsufferedmoderatetoseverepainatleastmonthly.Theresultsofthissurveychallengethebeliefthatcancerpainisusuallywellmanaged.Thestudyfoundthatpainwasprincipallymanagedbymedicaloncologists(42%,242/573).Mostpatients(72%,415/573)reportedthattheirclinicianaskedthemabouttheirpaineitheratmostconsultations(16%,95/573)oreveryconsultation(55%,320/573).Only15%(88/573)ofpatientsreportedthattheirclinicianmeasuredtheirpainusingapainscale(55%,320/573).Of441patients,437reportedthattheyusedprescriptionmedicationstotreatpain.Amongthese,24%weretakingastepIIIopioidalone,12%weretakingastepIIopioidalone,7%weretakingstepIIandstepIIIopioids,eithertogetherorincombinationwithnon-opioiddrugs,and8%receivednon-opioidanalgesicsalone.Eventually,painwasdescribedasdistressingby67%ofpatients,asanintolerableaspectoftheircancerby36%,and32%reportedthatthepainwassobadtheywantedtodie.BreivikH,ChernyN,CollettB,etal.Cancer-relatedpain:apan-Europeansurveyofprevalence,treatment,andpatientattitudes.AnnOncol.2009;26[Epubaheadofprint]**ThemostrecentstudyoftheprevalenceandmanagementofcancerpaininEuropeandIsraelthatdemonstratesthatatthemomentthetreatmentofcancerpainissuboptimal.

腫瘤內(nèi)科的疼痛管理WHO癌癥疼痛三階梯治療指南的目前的評價In1986theWorldHealthOrganization(WHO)publishedanalgesicguidelinesforthetreatmentofcancerpainbasedonathree-stepladderandpracticalrecommendations.TheWHOanalgesicladderremainstheclinicalmodelforpaintherapy.TheseandsimilardatasuggestthatadirectmovetothethirdstepoftheWHOanalgesicladderisfeasible.

腫瘤內(nèi)科的疼痛管理WHO癌癥疼痛三階梯治療指南的目前的評價Opioidsarethegold-standardtreatmentinmoderatetoseverepain.TheWorldHealthOrganization(WHO)in1986establishedastepwiseapproachforthetreatmentofpatientswithcancerpain.Thegoalwastoprovidetreatmentguidelinesthathealth-carepractitionerscouldeasilyfollow.NumerousstudieshaveshownthatwhentheWHOtreatmentguidelinesarefollowed,90%ofpatientsarepain-free.腫瘤內(nèi)科的疼痛管理WHO癌癥疼痛三階梯治療指南的目前的評價Thesepainmanagementguidelinessuggestthatthechoiceofanalgesicpharmacotherapyshouldbebasedontheintensityofpainreportedbythepatient,notsimplyonitsspecificetiology.IntheWHOguidelines,morphineremainsacornerstoneforthemanagementofcancerpain.Asubstantialminorityofpatientstreatedwithoralmorphine(10–30%)donothaveasuccessfuloutcomebecauseofexcessiveadverseeffects,inadequateanalgesia,oracombinationofbothadverseeffectstogetherwithinadequateanalgesia.Itisnowrecognizedthatindividualpatientsvarygreatlyintheirresponsetodifferentopioids.Patientswhoobtainpooranalgesicefficacyortolerabilitywithoneopioidwillfrequentlytolerateanotheropioid.Opioids,suchasmorphine,hydromorphone,oxycodone,fentanyl,andbuprenorphine,havebeenshowntobehighlyeffectiveinalleviatingmoderatetoseveremalignantpain.腫瘤內(nèi)科的疼痛管理WHO癌癥疼痛三階梯治療指南的目前的評價Recently,thedevelopmentofnewdrugsandformulationsofdifferentopioidshasenlargedtheavailabletherapeuticarsenalandimprovedtheiradministration,thuscontributingtobettertoleranceofsideeffects.Thishasmodifiedthethirdstepinanalgesia,andmorphinedoesnotremainthefirst-choicedrug.腫瘤內(nèi)科的疼痛管理WHO癌癥疼痛三階梯治療指南的目前的評價However,theroleoftheweakopioidsinthetreatmentofmoderatecancerpainhasbeenquestioned,andsomeexpertsspeculatethatthissecondstepoftheladdercouldbeomitted.MarinangeliF,CiccozziA,LeonardisM,etal.Useofstrongopioidsinadvancedcancerpain:arandomizedtrial.JPainSymptomManage.2004;27:409–16.*Thisarticlespeculatesthatsecondstepoftheladdercouldbeomitted.

腫瘤內(nèi)科的疼痛管理弱阿片類藥物在二階梯治療中的地位受到質(zhì)疑Whiletheuseofnon-opioidsforstepIand“strong”opioidsforstepIIIiswidelyaccepted,theclinicalusefulnessofthe“weak”opioidsinthemanagementofcancerpainhasbeenchallenged.Therearetwosystematicreviewscomparingtheefficacyofnonsteroidalanti-inflammatorydrugs(NSAID)versusaweakopioid.[1，2]TheresultssuggestthatthetransitionfromstepItostepIIdrugsdoesnotnecessarilyimproveanalgesia.Furthermore,thistransitionmaydelayachievingoptimalpaincontrol,especiallyinpatientswithrapidlyprogressivepainorinthosewhoneedquicktitrationofanalgesictherapy.1.EisenbergE,BerkeyCS,CarrDB,MostellerF,ChalmersTC.Efficacyandsafetyofnonsteroidalantiinflammatorydrugsforcancerpain:ameta-analysis.JClinOncol.1994;12:2756–65.2.McNicolE,StrasselsS,GoudasL,LauJ,CarrD.Nonsteroidalanti-inflammatorydrugs,aloneorcombinedwithopioids,forcancerpain:asystematicreview.JClinOncol.2004;22:1975–92.腫瘤內(nèi)科的疼痛管理強阿片類藥物一線治療疼痛的臨床試驗Theefficacyandtolerabilityofstrongopioidsasfirst-linetreatmentcomparedwiththerecommendedWHOregimenwasanalyzedinaphaseIIIstudyperformedin100terminalcancerpatientswhosufferedfrommildtomoderatepain.Patientswhowerestartedonstrongopioidsnotonlyhadsignificantlybetterpainrelief,buttheyalsorequiredsignificantlyfewerchangesintherapy,hadgreaterreductionsinpainwhentherapeuticchangeswereinitiated,andreportedgreatersatisfactionwithtreatment.Nodifferenceswereobservedinqualityoflifeorperformancestatusbetweenthetwogroups.Thesedatasuggesttheutilityofstrongopioidsforfirst-linetreatmentofpaininpatientswithterminalcancer.[1]

1.MarinangeliF,CiccozziA,LeonardisM,etal.Useofstrongopioidsinadvancedcancerpain:arandomizedtrial.JPainSymptomManage.2004;27:409–16.腫瘤內(nèi)科的疼痛管理疼痛視覺量表評分>5是治療的關鍵Experiencereportedsinceitsapplicationmorethan20yearsago,aswellasthedeeperunderstandingofthedifferenttypesofpainandthereleaseofbrandnewtherapeuticformulations,havecurrentlyledustoconsidernewchangesinthisuniqueanalgesictreatmentmodel,thususefulinchoosingthebesttherapyaccordingtothetypeofpainandnotonlyitsseverity.Asaresult,someexpertssuggestthe"analgesicelevator"model.Incontrasttotheladderconcept,thismodelleadsustotheconceptofimmediateresponse,sincethetransportofanalgesicsinsidealiftwouldbequickerthansteppingupaladder.ThishighlightshowimportantitistoperformacontinuousevaluationforpainbasedonthePainVisualAnalogSeverityScale(PVASS).Infact,ascore>5onthisscaleshouldmakeusbealertandprovidethelevelofanalgesiarequiredimmediately.TorresLM,CalderónE,PerniaA,Martínez-VázquezJ.[Fromthestairstotheescalator].RevSocEspDolor.2002;9:289–90.腫瘤內(nèi)科的疼痛管理MorphineDosesneedtobeindividualizedbioavailabilityisvariable(15–65%)Serumlevelshaveapeakatapproximatelyonehour.Clearanceisvariableandmediumeliminationhalf-liferangesfrom3–4hours(1–7).Thisdeterminesthewayofadministration.Comparativeclinicalstudieshaveshownnodifferenceamongthedifferenttypesofopioidsavailableintermsofsymptomcontrolandsideeffects.Oneretrospectivecohortstudyincluding12,000patientscomparedefficacyandadverseeventsamongtransdermalfentanyl,controlled/extended-releasemorphine,andoxycodone,findingnodifferenceeitherinpaincontrolorinthegastrointestinalside-effectprofile.WeschulesDJ,BainKT,ReifsnyderJ,etal.Towardevidence-basedprescribingatendoflife:acomparativeanalysisofsustained-releasemorphine,oxycodone,andtransdermalfentanyl,withpain,constipation,andcaregiverinteractionoutcomesinhospicepatients.PainMed.2006;7:320–9.腫瘤內(nèi)科的疼痛管理FentanylFentanylisaselectiveμ-receptoragonist.Comparedtomorphine,itisapproximately100-timesmorepotent,1,000-timesmorelipophilic,anditfeaturesalowermolecularweight.Fentanylismetabolizedprimarilyintheliver.Inhumans,invitroexperimentshavedemonstratedthatfentanylismetabolizedmainlybycytochromeP4503A4(CYP3A4)tonor-fentanylviaoxidativeN-dealkylation.Itsclearancehalf-lifeisshortandtheeffectofasingleoraldoselastsfor30minutes.[26]Oral(enteral)bioavailabilityoffentanylispoorandhencetheusualroutesofadministrationareintravenous,subcutaneous,spinal,transdermal,andtransmucosal.腫瘤內(nèi)科的疼痛管理FentanylFentanylisrecommendedforpatientswhoseopioidrequirementsarestableatalevelcorrespondingto≥60mg/dayofmorphine.JostL,RoilaF.ESMOGuidelinesWorkingGroup.Managementofcancerpain:ESMOClinicalRecommendations.AnnOncol.2008;19(Suppl2):ii119–21.腫瘤內(nèi)科的疼痛管理TransdermalFentanylTTSOncethepatchisplaced,fentanylserumlevelsincreaseuptoanalgesicconcentrationsin6–12hours,remainingstablefrom12–24hoursanddecreasingduringthefollowing48hours.Onesingleadministrationevery72hoursreachesstableserumfentanyllevels.Afterremovingthepatch,serumlevelsoffentanylprogressivelydecreaseuntil50%in17hours.Itsbioavailabilityis92%,andthereleasedamountofthedrugcorrelateswiththesizeofthepatch.腫瘤內(nèi)科的疼痛管理OraltransmucosalfentanylcitrateFentanylIontophoreticTransdermalSystem

FentanylSublingualTablet

腫瘤內(nèi)科的疼痛管理Fentanylcitratenasalspray,TAIFUN?.腫瘤內(nèi)科的疼痛管理Oxycodonefirst-stepmetabolizationinliver,whichexplainsits60–87%bioavailability.Oxycodoneserumhalf-lifetimeisdoublethatofmorphine(3–5hours)andreachesstationaryconcentrationsin24–36hours.Oxycodoneinteractswithseveralmedications,includingselectiveserotoninreuptakeinhibitors,cyclosporine,andrifampin.SelectiveserotoninreuptakeinhibitorsinhibitoxycodonemetabolismbyCYP450,whichleadstohigherconcentrationsandincreasedtoxicity.腫瘤內(nèi)科的疼痛管理Oxycodonecomparisonbetweenoxycodoneandmorphineincombinationversusmorphinealoneandprovedthattheconcomitantadministrationexhibitedabetteranalgesiaprolessincidenceofemesis.LaurettiGR,OliveiraGM,PereiraNL.Comparisonofsustained-releasemorphinewithsustained-releaseoxycodoneinadvancedcancerpatients.BrJCancer.2003;89:2027–30.腫瘤內(nèi)科的疼痛管理OxycodoneOncancerchronicpain,fiveclinicaltrialshavebeenpublishedcomparingcontrolled-releaseoxycodoneversuscontrolled-releasemorphine(fourtrials)andversushydromorphone(onestudy).Themainefficacyendpointwastheperceptionofpainreportedbypatientsthemselves,measuredasascoreonPVASSorastheamountofrescuemedicationneeded.Nosignificantdifferencesinefficacywereproven,butinasinglestudy[56]resultsweremorefavorabletomorphine.Ingeneral,thelimitednumberofpatientsrecruitedmakesthesestudiesdifficulttoevaluateproperly.Theirimportance,ontheotherhand,liesinthefactthatthesestudieshelpeddetermineequianalgesicdoses.Thus,intermsofequianalgesicefficacy,1mgoxycodonedosecorrespondsto1.5mgofmorphine,[55–58]whereasone1mgoxycodonedosecorrespondsto0.25mgofhydromorphone.[59]

腫瘤內(nèi)科的疼痛管理ThematchofoxycodoneandnaloxoneAgonistAntagonistNaloxoneOxycodoneTargin@

腫瘤內(nèi)科的疼痛管理OxycodoneNaloxone

Targin@

TheinnovativeprincipleAchievingpotentanalgesia;Treatmentand/orprophylaxisofopioidinducedconstipation;Improvedqualityoflifeandcompliance.腫瘤內(nèi)科的疼痛管理innovative腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理總結Since1986,theapplicationoftheWHOstepladderanalgesicregimenhasallowedabettercontrolofpainandwillachievepainreliefinthemajorityofpatientswithcancer.Between70–90%ofpatientswithcancerpaintreatedaccordingtothethree-stepladderachieveseffectiveanalgesia.Experiencereportedsinceitsapplicationmorethan20yearsagosuggeststheutilityofstrongopioidsforfirst-linetreatmentofpaininpatientswithterminalcancercouldbebetter,especiallyforpatientswithmoderatetoseverecancerpain.RecentupdatesabouttheprevalenceandtreatmentofcancerpaininEuropehavedemonstratedthatassessmentispoorandtreatmentandoutcomesareoftensuboptimal.Itisnecessarytoimprovepainmanagementinmoderatetoseverecancerpain.Opioidsarethegold-standardtreatmentinmoderatetoseverepainandintheWHOguidelines;morphineremainsacornerstoneforthemanagementofcancerpain.Recently,thedevelopmentofnewdrugsandformulationsofdifferentopioidshasenlargedtheavailabletherapeuticarsenal,modifyingthethird-stepinanalgesiaandmorphineisnottheonlyoption.腫瘤內(nèi)科的疼痛管理腫瘤內(nèi)科的疼痛管理我國腫瘤病人疼痛處理中問題現(xiàn)狀1.管理上較為嚴格，有需要的病人不能合理或及時的得到相應的符合標準的處理。2.病人家屬及病人自己的問題，不愿意及時使用強阿片類藥物。3.病人的經(jīng)濟問題。4.藥物品種的缺少。尤其在基層醫(yī)院。5.病人的教育。6.醫(yī)務人員對腫瘤病人疼痛的不作為。7.藥品企業(yè)對疼痛產(chǎn)品開發(fā)的不足。8.缺少相應的符合國情的疼痛治療指南。9.對于難治性疼痛缺少共識。10.缺少專業(yè)的隊伍，包括心理，護士和?？漆t(yī)生。腫瘤內(nèi)科的疼痛管理管理上較為嚴格，有需要的病人不能合理或及時的得到相應的符合標準的處理。1.由于國家政策的限制，現(xiàn)行的麻醉藥品管理較為嚴格。2.表現(xiàn)為：1.病人用藥量有限制2.針劑控制3.藥品品種不全，劑量不全4.地域差異明顯5.處方醫(yī)生限制腫瘤內(nèi)科的疼痛管理病人家屬及病人自己的問題，不愿意及時使用強阿片類藥物1.由于歷史原因，國人對于使用阿片類藥物有一事實上的恐懼心理，不愿