阿片 成瘾 英文

OpiateDependentPatients:

ManagementStrategiesintheUnitedStates

MichelleRainka,Pharm.D.,CCRPDentInstituteUniversityatBuffalomrainka@mmrainka@Copyright©:ReproductionoftheseslidesisprohibitedwithoutpermissionoftheauthorOpiatedependentmanagementobjectivesKnowthefollowingsubstanceabusevocabulary:opiateagonist,opiateantagonist,partialagonist,withdrawal,tolerance,addiction,drugabuse,dependenceIdentifyeffectsofabuse,includingsignsandsymptomsoftoxicity/withdrawalDiscusstreatmentoptionsforpatientsRecommendtreatmentsforoverdose,dependence,withdrawal,andmaintenance.SubstanceUseDisorder

Facts&Figures-UnitedStates22.2millionpeople12orolder(8.5%ofthepopulation)livewithsubstancedependenceorabuse2.1millionAmericanslivewithpainrelieveropioidaddictiondisease,while467,000AmericanslivewithheroinopioidaddictiondiseaseNearly100Americansdieeachdayfromopioidoverdose-60%menand40%womenAbout3,000AmericansdieannuallyfromheroinoverdoseAbout75%ofopioidaddictiondiseasepatientsswitchtoheroinasacheaperopioidsource/docs/default-source/advocacy/asam---opioid-addiction-disease-facts-figures-2014.pdf?sfvrsn=0VocabularyAddiction:aprimary,chronic,neurobiologicaldiseaseorbehavioralsyndrome,withgenetic,psychosocial,andenvironmentalfactorsinfluencingitsdevelopmentandmanifestationsChronicity,impairedControloverdruguse,Compulsiveuse,Continuedusedespiteharm,CravingDrugAbuse–maladaptivepatternofsubstanceusecharacterizedbyrepeatedadverseconsequencesrelatedtotherepeateduseofthesubstanceVocabularyDiagnosticandStatisticalManualofMentalDisordersdefinesDependenceas-atleast3ofthefollowing:ToleranceWithdrawalLargeramountsorlongerperiodoftimethanwasintendedPersistentdesireorunsuccessfulefforttocutdownorcontrolTimespentinactivitiesnecessarytoobtain,use,orrecoverSocial,occupational,orrecreationalactivitiesgivenuporreducedContinueddespiteknowledgeofhavingapersistentorrecurrentphysicalorpsychologicalproblemcausedorexacerbatedbysubstanceAmericanPsychiatricAssociation

DiagnosticandStatisticalManualofMentalDisorders,4thEdition,TextRevision(DSM-IV-TR)June,2000ToleranceTolerance–astateofadaptationinwhichexposuretoadruginduceschangesthatresultinadiminutionofoneormoreofthedrug’seffectovertimeShiftingDoseResponseCurvetotheright2typesMetabolicLiverenzymesCellularReceptordown-regulationAcutevs.ProtractedAcuteiswithinasingleadministrationCross-toleranceTolerancetoonedrugleadstotoleranceofotherdrugsinthesameclass.DOSERESPONSEtolerancePhysicaldependenceisassociatedwith,butseparatefrom,tolerance.Thepatientneedsthedrugtofunctionnormallyandtoavoidwithdrawalsymptoms.Dependence/WithdrawalPhysiologicalDependenceBodyadaptstopresenceofdrug.Needsdrugonboardtomaintainhomeostasisspecificwithdrawalsymptomscanbeproducedbyabruptcessation,rapiddosereduction,decreasingbloodlevelofadrugand/oradministrationofanantagonistWithdrawalsymptomsBehaviorsdisplayedbyauserwhendruguseendsTypicallytheoppositeofthedrugeffectRepeatedSelf-AdministrationMesolimbicdopaminesystemAbuseddrugsalltendtoactivatethissystem3stagesPleasureAssociativelearningthroughclassicalconditioningIncentivesalienceCraving(wanting)GetDAreleasebycues/contextaloneEffectsonNeuralSystemsActivationofmesocorticolimbicsystemReinforcement:NeurochemicalsystemsEnkephalinInhibitoryNeuronREWARDGlutamateExcitatoryInputEnkephalinorDynorphinInhibitoryNeuronGABAInhibitoryNeuronGABAInhibitoryFeedbackDopamineNeuronGABANeuronVentralTegmentalArea(VTA)NucleusAccumbens(NAc)DopamineReceptorsGABA-AReceptorsPresynapticOpioidReceptors(m,d?)mOpioidReceptorskOpioidReceptorsTreatmentPharmacotherapyOutpatient/Inpatient(acutevslongterm)addictionTreatmentCounselingGroups:NarcoticsAnonymousToxicologyTestingIdentifyingco-morbidconditions–History,PhysicalExam,Neurologicalexam,laboratory:LaboratoryVitaminD,B12,iron,folate,liverfunctiontests,thyroid,Hematology,MetabolicPanel,HIV,HepatitisCPsychiatricdiagnosisMostcommon:othersubstances,PTSD,substance-inducedpsychiatricdisorders,antisocialandborderlinepersonalitydisorderBipolar,schizophrenia,depression,anxietyOtherhealthissuesHepatitis,HIV/AIDS,ConcernswithsharingneedlesESAPprogramsExpandedsyringeaccessprogramSexuallyTransmittedDiseases–HIV/AIDSHepatitisTetanusAnaphylaxisNephroticsyndromeSepticemiaEndocarditisAbscesses–“skinpopping”VocabularyOpiateagonist:DrugsthatactivateopiatereceptorsonneuronsRepeatedadministrationleadstophysicaldependenceandtoleranceOpiateantagonist–opiatesthatbindtoopiatereceptorsbutblockthemratherthanactivatingthemOpiatepartialagonists–drugsthatbindtoopiatereceptors,butnottothesamedegreeasfullagonists.ceilingeffectOpiateagonistsMechanismofActionBindstoopiatereceptorsintheCentralNervousSystem,causinginhibitionofascendingpainpathways,alteringtheperceptionofandresponsetopain;producesgeneralizedCNSdepressionHeroin,morphine,codeine,hydrocodone,hydromorphone,fentanyl,oxycodone,tramadol,tapentadol,meperidineBymouth,intravenous,insufflation,subcutaneously,IntramuscularlyMechanismofAction:

FullopioidagonistTheopioidreceptorisempty.Assomeonebecomesmoretoleranttheybecomelesssensitivetothemedications.Thepatientisexperiencingpain,thisiswhenwithdrawalhappens.Theopioidreceptorisfilledwithfullagonist.Thereceptorisfullyactive.Drugssuchasheroinandpainkillerscancauseeuphoriaandstopwithdrawalforsometime.OpiatesEffectsEuphoriaDysphoriaApathyMotorretardationSedationSlurredspeechAttentionimpairmentMiosisConstipationWithdrawal(notfatal,notdelirious)LacrimationRhinorrheaMydriasisPiloerectionDiaphoresisDiarrheaYawningFeverInsomniaMuscleache/pain“kickingthehabit”OverdoseOverdose:supportive,Naloxone0.4-2mgIVq3minifunconsciousandrespiratorydepressedNaloxone:MechanismofActionPureopioidantagonistthatcompeteswithanddisplacesnarcoticsatopioidreceptorsitesSKOOPProgram-TheHarmReductionCoalition’sSKOOP(SkillsandKnowledgeonOverdosePrevention)–Provideseducation,needleexchangeandemergencyaccesstonaloxoneOpiatesWithdrawal:Methadone–since1960sLAAM–levo-alpha-acetylmethadol–2003discontinuedinUSBuprenorphine:4mg-32mg/day–since2002Clonidine.Maintenance:Methadone–since1960sLAAM–levo-alpha-acetylmethadol-2003discontinuedinUSBuprenorphineAbstinenceNaltrexone-bymouthorintramuscularlyMethadoneDetoxorMaintenanceMechanismofActionBindstoopiatereceptorsintheCNS,causinginhibitionofascendingpainpathways,alteringtheperceptionofandresponsetopain;producesgeneralizedCNSdepressionSubstrateofCYP2C9(minor),2C19(minor),2D6(minor),3A4(major);InhibitsCYP2D6(moderate),3A4(weak)Half-lifeelimination:4-91hours;maybeprolongedwithalkalinepH,decreasedduringpregnancyQTprolongationMethadonedetoxWithdrawal:Withdrawal-Methadone20-80mg,taperby5-10mgdailyMethadonemaintenance3objectives:SuppresssignsandsymptomsofopiatewithdrawalExtinguishopiatecravingBlockthereinforcingeffectsofillicitopiatesMethadoneMaintenanceInduction(priortosteadystate):Halfofeachday’sdoseremainsinthebodyandisaddedtothenextday’s,increasinglevelswithoutincreasingdose-startlow,goslowInitialdosenotgreaterthan30mgor40mginday1Nocorrelationbetweentroughorpeaklevelsatdosesabove100mg/dayPeaklevelsshouldbenomorethantwicethetroughs/scanbemosteffectiveindicatorsRelievewithdrawal–adequacybasedon3-8hReachtolerance,reducecravingEstablishadequatedoseMaintenace=preservationofdesiredeffectsCompletephysicalexamandlabswithin14daysLeavittSBMethadoneDosingandSafetyIthetreatmentofopiateaddiction.AddictionTeatmentForum2003MethadoneMaintenanceTakehome:Dependsonlongevityinprogram(2days/weekin1st90daysto1monthafter2years)CapableofhandlingandtakingunsupervisedAbstinencefromunauthorizedsubstancesRegularattendanceAbsenceofbehavioralorcriminalissuesStablehomeandsocialenvironmentsMethadonecanbesafelystoredLeavittSBMethadoneDosingandSafetyIthetreatmentofopiateaddiction.AddictionTeatmentForum2003BuprenorphineMechanismofActionBuprenorphineexertsitsanalgesiceffectviahighaffinitybindingtoμopiatereceptorsintheCNS;displayspartialmuagonistandweakkappaantagonistactivitySubstrateofCYP3A4(major);InhibitsCYP1A2(weak),2A6(weak),2C19(weak),2D6(weak)Activemetabolite=norbuprenorphineMechanismofAction:

PartialOpioidAgonistBuprenorphinereplacedthefull-opioidagonists.Buprenorphinecompeteswiththefullagonistsforthereceptors.Buprenorphinehashigheraffinitysoitisabletodisplacefull-agonists.Italsohaslimitedopioideffectstostopwithdrawalsymptoms.Overtime24-72hours,buprenorphinedissipateshoweveritstillhaslimitedopioideffectsandcontinuestoblockotheropioidsfromattachingtothereceptor.BuprenorphinemanagementCandidatesNotmerelyphysicallydependent,butalsoaddictedNocontraindicationsInterestedExpectedtobereasonablycompliantWillingtofollowsafetyprecautionsWillingafterreviewoftxUnlikelycandidatesComorbiddependenceonotherCNSdepressantsSignificantuntreatedpsychActive/chronicSI/HIMultipletx/relapsesPoorresponsetosuboxoneComplexmedicalTreatmentImprovedProtocol(TIP)40:ClinicalGuidelinesfortheuseofBuprenorphineinthetreatmentofOpioidAddiction(2004).HHSBuprenorphinemanagementMaintenancetxwithBuprenorphineInduction–Switchingpatientsfromopiatestobuprenorphine,findingtheminimumdoseatwhichthepatientdiscontinuesormarkedlydiminishesuseofopiates,experiencesnowithdrawal,minimalornosideeffectsandnocravings.Stabilization–Markedbytheptexperiencingnowithdrawal,minimalornosideeffects,nolongeruncontrolledcravings,ptsseenweeklyMaintenance–Maybeindefinite,attentiontopsychosocialissues,seen/toxedmonthlyTreatmentImprovedProtocol(TIP)40:ClinicalGuidelinesfortheuseofBuprenorphineinthetreatmentofOpioidAddiction(2004).HHSMedicallysuperviseddetoxwithBuprenorphineToprovideatransitionforanopiatephysicallydependentstatetoanopiatefreestate.InductionDosereductionTreatmentImprovedProtocol(TIP)40:ClinicalGuidelinesfortheuseofBuprenorphineinthetreatmentofOpioidAddiction(2004).HHSBuprenorphineDetox/WithdrawalORMaintenance:Buprenorphine:4mg-32mg/daySubutex=Buprenorphine2mgor8mgSuboxone=buprenorphine/naloxoneSuboxone12/3mgslFilmSuboxone8/2mgslTablets/FilmSuboxone4/1mgslFilmSuboxone2/0.5mgsltablets/FilmZubsolv=buprenorphine/naloxoneZubsolv5.7/1.4mgslTabletsSuboxone1.4/0.36mgsltabletsBunavail=buprenorphine/naloxoneBuccalFilms6.3mgbuprenorphine-1mgNaloxone4.2mg-0.7mg2.1mg-0.3mgZubsolv&SuboxoneClinicalData:758patientswerestudiedtolookattransitioningpatientsfromSuboxonetoZubsolvZubsolvshowedcomparableretentiontoSuboxoneNostatisticaldifferenceincravingswerenotedbetweenthetwomedicationsNostatisticaldifferencebetweenadverseeventsassociatedbetweenSuboxoneandZubsolvFischerA,JönssonM,HjelmströmP.Pharmaceuticalandpharmacokineticcharacterizationofanovelsublingualbuprenorphine/naloxonetabletformulationinhealthyvolunteers.DrugDevIndPharm.2013;1-6/healthcare-professionalsZubsolv&SuboxoneThebioavailabilityofZubsolvcomparedtoSuboxoneZubsolvcontainslessbuprenorphineandnaloxonecomparedtoSuboxoneThehigherbioavailabilityofZubsolvallowsforalowerdoseofbuprenorphineandmayhelptoreducepotentialmisuseand

diversionThisgraphindicatesthatbothZubsolvandSuboxonereachsimilarconcentrationinthebodyZubsolv&SuboxoneDoseconversionSuboxone

Zubsolv8mg/2mg

5.7mg/1/4mg2