managing djd: introduction - vetgirl · managing djd: the nsaids matt brunke, dvm, ccrp, cvpp, cva...
TRANSCRIPT
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ManagingDJD:
theNSAIDSMattBrunke,DVM,CCRP,CVPP,CVAACVSMRCareerPathCandidate
GarretPachtinger,VMD,DACVECC
COO,VETgirl
Introduction
JustineA.Lee,DVM,
DACVECC,DABTCEO,VETgirl
Introduction
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Cecertificates
• MattBrunke,DVM,CCRP,CVPP,CVA
• ACVSMRCareerPathCandidate
Speakerintroduction
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Alittleaboutme…..Iliketokeepbusy
HowmanyofyouseeDJD/OA?
• CCLDz• HipDysplasia• ElbowDysplasia• OCD• Trauma• Athletic/WorkingCanines• Obesity• Conformationissues
Osteoarthritisisthe#1CauseofChronicPaininDogs
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1.GaynorJetal.TheEssentialGuidetoPainManagement:AcompleteResourceforVeterinaryPainManagement2003.2.JohnstonSA.VetClinNAmSmallAnimPract27:699-723;1997.
• Chronicpain
• Decreasedactivity
• Anoverallnegativeimpactonthepatient
• Interfereswithhuman-animalbond
• Decreasedfoodintake
• Euthanasiafordogsthatbecomenon-responsivetotreatment
Impact
Affects20%ofDogsinU.S.
WhenareyoufindingOA/DJDpatients?
• Everyexamyoudo!– DOGSandCATS• Especiallygeriatrics – ageisNOTadisease• Knowyournormal– flex/extendeverypatient• History?’s– troublewithstairs?Lessactive?• Feelfor:jointthickening,musclewasting,decreasedelbowflexion,decreasedhipextension
• Lookfor:scuffmarksonnails,poorposture,swayback,unevenpadwear
• CartilagedamageoccursWAYbeforeradiographicchanges
PathophysiologyofOA/DJDinvolvestheentirejoint
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CartilagedamageinitiatesOA/DJD• Initialtrauma=fibrillationofcartilagesurface,damagetochondrocytes,releaseof:
• Cartilagedegradationproducts(CDPS)
• Matrixmetalloproteinases(MMPs)• Nitricoxide(NO)andinflammatorycytokines
• MMPs/CDPSareengulfedbysynoviocytes,whichrelease:
• Inflammatorymediators:PGE2,TNF,IL1b andMMPs
• Allcontributetocycleofinflammation,degradationandpainofosteoarthritis
InitialCartilageDegradation
EndStageCartilageDegradation
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OtherChangesinOA/DJD
• ThickeningofJointCapsule• Remodelingofsubchondralboneè sclerosis• Osteophyteformation
• SynoviocytesreleaseBoneMorphogeneticProteins(BMPs)• Periosteummesenchymalstemcelltodifferentiateintochondrocytes• Initiateosteophyteformationè jointmouseorimpingeonperiosteum
• Bottomline:OAbecomesaviciouscycle• Jointislessabletobearstressandforces:
• Furtherjointdamage• Clinicalsigns
Pro-inflammatoryMediatorsCauseProgressiveJointDamage
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1.PelletierJPetal.ATextbookofRheumatology,KoopmanW(ed).14thEd:2195-2245.Lippincott,WilliamsandWilkins;Baltimore,2000.
2.CleggPDetal.EquineVetJ.29:335-342;1997.3.Martel-Pelletieretal.FrontiersinBioscience4:D694-D703;1990.
Pro-inflammatoryMediators• PGE2• IL-1,IL-6,TNFMatrixMetalloproteinases
SynoviocytesReleasePro-inflammatorymediators(TNFandIL-1b)MMPs
Pro-inflammatoryMediatorsCauseProgressiveJointDamage
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1.PelletierJPetal.ATextbookofRheumatology,KoopmanW(ed).14thEd:2195-2245.Lippincott,WilliamsandWilkins;Baltimore,2000.
2.CleggPDetal.EquineVetJ.29:335-342;1997.3.Martel-Pelletieretal.FrontiersinBioscience4:D694-D703;1990.
OngoingInflammationistheSourceofBoththeProgressiveNatureandPainofOsteoarthritis
• ProstaglandinE2(PGE)andotherinflammatorycytokinesleadto:• Progressivedegradationofthejoint• Stimulationofnociceptorsinsynovium,jointcapsuleandsubchondralbone
• PGEisalsoreleasedindorsalhornandcontributestothepainsignal
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JohnstonSA.VetClinNA,SAP,31:39-53:2001.
JointInflammationisOneSourceofPaininOA/DJD
• Cartilageisanueral;cartilagedamagealoneisnotpainful• Inflammationstimulatesnociceptorsfoundin:
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• Thejointnociceptorsinitiatepathologicalpain
JointCapsule Synovium
SubchondralBone Periosteum
NeurogenicInflammation
• Isanadditionalstepinthenociceptivepathway• Involvetheantidromic releaseofneurotransmittersnearthejoint• NeurotransmitterssuchasSubstancePè inflammatorymediatorswithinthejoint
• Contributestojointpainandinflammation
1.JohnstonSA.VetClinNA,SAP,31:39-53;2001.2.CoutauxA,etal.JointBoneSpine.,72:359-371;2005.
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Pro-inflammatorymediatorsinitiatepainandhyper-sensitizetheCNS
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1. CamuF,Shil,VanlersbergheC.Drugs.63Suppl1:1-7;2003.2. JohnstonS.VetClinicsofNA:SmallAnimalPractice,31:39-53;2001.
1.Johnston,SA.VetClinNAmSmallAnimPract27:699-723;1997.2.CamuF,etal.Drugs.63Suppl1:1-7;2003.3.MuirWW.VeterinaryPainManagement,Gaynor,JandMuirWW.(Eds),Mosby,Columbus2003.
SummaryofInflammatoryProcessofOA
• OAisachronicprogressivelydestructivediseasethatinvolvestheentirejoint• Inflammationisakeycomponentofbothjointdestructionandpain• Acutepainresolvesaftertheinitialinjuryheals• Chronicpaininvolvesstructuralchangesofthedorsalhorn,ismoreintensethanacutepain,andmoredifficulttocontrol
• TreatmentconsiderationsforOAshouldaddressinflammationaswellaspain
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Multimodalapproach NSAIDisthecornerstoneoftherapy
• Quickaction• Anti- “itis”
• Butwhathappenswhen:• Ownerdeclinesit?• Patientcan’ttakeit?• It’snotworking?• Wehavelostthepharmacy?
NutritionOptions/Goals
• Minimizeobesity• Keepupproteininseniorpets–keepmusclemass
• FortifiedwithOmega-3’s
Obesity– aheavyissue
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ObesityEffects- Two-fold
• Biomechanicalstresscontributestoclinicalsignsandprogressionofdisease
• Adipokinessecretedbywhitefatcellscontributetotheprogressiveinflammationofosteoarthritis
• Leptinlevelsareelevatedinobesedogs• Inhumanswithosteoarthritis,increaseleptinlevelscorrelatewithelevatedMMPsandNOinsynovialfluid
• Adiponectinisanti-inflammatory,butlevelsarelowinobesedogs
• Inhumanpatientswithkneeosteoarthritisthereisasignificantcorrelationwithadiponectin:leptinratios 1.CicuttiniFM,etal.JRheumatol.1996;23:1221-1226.
2.TodaY,etal.Rheumatol.1998;25:2181-2186.3.Marshalletal.VetCompOrthoTraumatol2009;5:339-345.
EffectsofweightlossonOA
• Humanswithincreasedbodymassindex(BMI)experienceOAinnon-weightbearingjoints,whichresolveswithweightloss
• DecreaseinBMI,isassociatedwithsymptomaticrelieffromkneeOAinman• Systematicreviewofcaninestudiesfound
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PreventingObesityDecreasesIncidenceofOA
WeightLossReducesSignsofOA
Omega-3dietsindogs Andcats!
Nutritionalsupplements
• Glucosamine• Chondroitin• MSM• ASU• More?• Atalkforanotherday
Rehabilitation(PhysicalTherapy)
PhysicalModalities • Therapeuticlaser,ultrasound,TENS,etc.
ManualTherapies• Jointmobilization• Massage• ROM,stretching
TherapeuticExercise– CoreofPT
• Corestrengthening• Weightbearing• Proprioception• Underwatertreadmill
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GoalofRehabilitationwithOA
BuildMuscleSupportAroundJoint
ReducePain
WeightLosswhenindicated
Maintain/ImproveMuscleMass
ReachingGoalswithRehab
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• Athometherapies
• In-clinicrechecksandtherapy
• Concurrentpainmanagementshouldbeconsideredaspartoftherehabilitationprogram
ProgramCanThenBeTailoredtoIndividualPatient
• Beginwithpatientassessment
– Determinemobilitystatus,limbgirth,rangeofmotion
– Assessbodyconditionscore
DeterminingGoal
Thermotherapy
Becreative.DON’TUSEELECTRIC HEATINGPADS.
LightAmplificationbyStimulatedEmissionofRadiation• Photobiomodulation• Activatecytokinesandothertissuefactors
• Decreasepainandinflammation• Increasewoundhealing• Alwaysusegoggles• Canuseinacupuncture• Notoncancerorpregnancy• AnotherlectureJ
ManualTherapy
• Skilledhandmovementtechniquesintendedto:• Improveissueextensibility
• IncreaseROM
• Inducerelaxation
• Mobilizeormanipulatesofttissuesandjoints
• Modulatepain
• Reduceswellingandinflammation
TherapeuticExercises
• Theoccupationaltherapyaspectofrehab• Buildongoingfromdowntoup,andthenmimickingthefunctionsneededtobeinanormalenvironment
• Returntofunction
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Cavaletti Rails Peanuts
BalanceBoardandRolls
• Corestrength- Yoga• Makesuregoodtraction• Useyourweighttohelpshift• Candojustfrontlimbsorhindlimbs
• Rhythmicstabilization
CoreStrengthening
Walking
• Agreatexercise• Onleash,continuousmovement– flatnon-slipsurfaces
• Atapaceappropriateforthepatient,nottheowner
• Startwith10-12minutestwiceaday,increaseeachweekby3-5minutes
• Addinhills,varyingtraction(sand,snow,highgrass)
Hydrotherapy– anotherpresentation
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Treadmills
• Diagnostictoolalso• Safeandcontained• Feetalwaystouchingground• Buoyancy• Takesafewseconds/minutetogetthemusedtoit
Polysulfated Glycosaminoglycan• FDAapproved,diseasemodifyingosteoarthritisdrugs;fordogsandhorses;water-based,forintramuscularInjection
• Dosage:2mg/lbbodyweight,IM,twiceweeklyforupto4weeks(maximumof8injections)
• MOA:specificisnotknown;invitrostudiesshow;• Inhibitserineproteinases;PGE2synthesis;metalloproteases,hyaluronidasesandothers
• Stimulatesynthesisofprotein,collagen,proteoglycans,andhyaluronicacid• Anecdotally“maintenance”injectionsmonthly• OfflabelSQusage• OfflabelfelineSQusage
• 1.Adequanprescribinginformation.NADA 141038,NovartisAnimalHealth,US,INC.
PolysulfatedGlycosaminoglycan–ClinicalStudies
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• Treateddogshadstatisticallysignificantimprovementinrangeofmotionandtotalorthopedicscoreoverplacebotreatedcontroldogs
Efficacy
• 2.1%ofdoghadadversereactionsincluding– Transientpainattheinjectionsite(1incident)– Transientdiarrhea(1incidenteachin2dogs)– Abnormalbleeding(1incident)– Theseeffectsweremild,self-limiting;didnotrequireinterruptionof
therapy
Safety
• DonotuseindogsshowinghypersensitivitytoPSGAG,orindogswithknownorsuspectedbleedingdisorders
• Usewithcautionindogswithrenalorhepaticimpairment
OtherDiseaseModifyingOADrugs(DMOAD)
• Zydax – Pentosan• Parnellproduct,availableinAustralia,maybecomingtotheUS
• Potentialbenefitforhorses• Noevidenceindogscurrently
AdjunctAnalgesics• UseinadditiontoorasareplacementforNSAIDS• Amantadine– onlydrugstudiedtotreatcanineosteoarthritis
• IndogswithosteoarthriticpainrefractorytoanNSAIDs,additionofamantadineimprovedphysicalactivity
• Mightbeausefuladjuncttherapyfortheclinicalmanagementofcanineosteoarthriticpain.
• 3-5mg/kgSID,catstoo
• Gabapentin– Calciumchannelmodulator– catsanddogs• 5-10mg/kgSID-TID
• Amitriptyline– SSRI– norepinephrine- catsanddogs• 0.5-1.0mg/kgSID-BID
• 1.LascellesBDX,etal. JVetInternMed.22(1):53-9,2008.
MoreAdjunctAnalgesics
• Acetaminophen– dogsnotcats.• 10-15mg/kgTID(bridgedrug)
• Localanesthetics– Lidocaine,bupivacaine,mepivacaine• Opioids– morphine,meperidine,methadone,oxymorphone,hydromorphone,fentanyl,fentanylpatches,butorphanol,pentazocine,nalbuphine,buprenorphine,codeine
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Tramadol• Metabolismandeliminationisrapidandvariableamongdogs• Whenadministeredorallyorintravenouslytothedog,metabolismoftramadolandallmetabolitesisrapid
• Thereismuchvariabilitybetweendogs,possiblybreeds• Paincontroldidnotnecessarilycorrelatewithplasmalevelsoftheactivemetabolite(O-desmethyltramadol)
• Affectsona-adrenergicorserotoninreceptorsmaycontributetoanalgesiceffectsinthedog
• Regardlessofmechanismofaction,studiessuggestoraldoseshouldbe5mg/kgq6hoursor2.5mg/kgq4hours
• AdditionallystudiesforaffectsincanineOAareneeded• 1.KukanichB,PapichMG.JVetPharmacolTherap.27,239-246:2004.
• 2.GiorgiMetal.VetResCommun33,875-885:2008.
• 3.KukanichB,PapichMG.AJVR.72,256-262;2011.
WhatisGALLIPRANT®(grapiprant tablets)?
• Galliprant isafirst-in-classnon-cyclooxygenase(COX)inhibiting,non-steroidalanti-inflammatorydrug(NSAID)inthepiprant class.
• Piprants areanewlyrecognizeddrugclass,establishedanddefinedbytheWorldHealthOrganizationin2013asprostaglandinreceptorantagonists(PRA).
• UniquemechanismofactionbyantagonizingtheprostaglandinE2(PGE2)EP4receptor.• PGE2itsphysiologiceffectsthroughbindingoffourdifferentreceptors,EP1,EP2,EP3andEP4.
• EP4receptorhasbeenidentifiedastheprimaryreceptorresponsibleformediatingpainandinflammationassociatedwithosteoarthritis.GALLIPRANTselectivelyblockstheEP4receptor,thusblockingPGE2elicitedpain.
Aratana - Galliprant® ESWT– ExtracorporealShockWaveTherapy• Shortdurationacousticwavesatlowfrequencyandhighpressure
• 100xatmosphericpressure inmicroseconds• Mechanismslacking– butreported
• reducedinflam/shorttermanalgesia• improvedvascularity,neovascularization• increaseboneformation• realignmentoftendonfibers• enhancedwoundhealing
• ImprovedweightbearingandcomfortableROMsimilartoNSAIDs
• Heavysedationoranesthesiausuallyrequired• Repeatingtreatmentq2-3weeksfor3-4treatments
• NoconcurrentNSAIDS
ESWTResearch ESWTResearch
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PEMF- PulsedElectromagneticFieldTherapy PEMF- PulsedElectromagneticFieldTherapy
PEMFResearch- Human PEMFResearch- Human
TCVM– TraditionalChineseVeterinaryMedicine
• Acupuncture• Electro– mostpublisheddata
• HerbalTherapy• FoodTherapy
Electroacupuncture forpain
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KinesiologyTaping
• Worksonlifting• Improvebloodflow,lymphaticreturn
• Painmitigation• Inflammation• Neurosensoryawareness
KinesiologyTaping– PainofOA/DJD MoreResearch
Intraarticular injections– TargetedTherapy
• Easytolearn• Sedated• Radiographs– verifythedisease• SterilePrep
IAInjections- Options
• Corticosteroids• HyaluronicAcid• RegenerativeMedicine
• PlateletRichPlasma(PRP)• StemCellTherapy
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IAInjections- Corticosteroids
• (20mg)ofmethyl-prednisoloneacetate
• Triamcinolone– 0.22mg/kgtotal
• Lesssystemiceffectswithtriamcinolone
IAInjections- HyaluronicAcid
• Increaseviscosityofjointfluid• Anti-inflammatory• Analgesic• Induceproductionofsynovialfluid
• Manydifferentoptions• Molecularweight
• Combinewithsteroid?
HA-article IAInjections– RegenerativeMedicine
• In-clinicandoutsideoptions• In-clinic– samedayharvestandtreatment,singleanesthesia
• Outside– culture,banking.• Buttwoanesthesiaepisodes
IAInjections– RegenerativeMedicine- PRP
• PlateletRichPlasma• 60ccofblood– 4ccofplatelets• Positiveeffectsonangiogenesisandextracellularmatrixremodeling
• Fibrinformatrix• Growthfactors–VEGF,TGFB,IL8• Cellproliferationanddifferentiation
• Stemcellrecruitmentandchemotaxis
Whichdoweuse?
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IAInjections– RegenMed– StemCells
• BoneMarrowvs.Adipose?• Contributetogeneratingnewtissue
• Chemotacticforprogenitorcells• Supplygrowthfactors• Makeextracellularmatrix• Angiogenesis• Anti-apoptosis• Anti-inflammatory• Anti-fibrotic
StemCellResearch
RecentResearch PromisingResults
TreatmentIA• MildOAandsynovitis
• HAweeklyx3weeksorsinglePRPinjection
• NoresponsetoHA,singlePRPinjection
• Acutepost-op(8-12weeks)• HAweeklyx3weeksorsinglePRP• IfnoresponsetoHA,singlePRPinjection
• ModerateOA• PRPinjectionweeklyx2injections(repeatifneeded)
• IfnoresponsecombinationMSC/PRP
• SevereOA• PRPeveryotherweekfor2-3treatments
Or• MSC/PRPcombinationfollowedbyboosterinjectionin9-12months
Or• IAsteroid
• 1injectionfollowedbya2nd ifneededin3-4weeks(maxof4injectionsperyear)
CopyrightS.Canapp 2017
TreatmentIA
• Expecteddurationoftreatment:• HA- 6monthsofrelief
• 80%respondwell• 10%respondfair• 10%don’trespond
• PRP- 9-12monthsofrelief• PRP/MSC- 18-24monthsofrelief
• Postregenerativemedicinetreatment• Noshockwavetx• Nolasers(4weeksforcells,2wks PRP)• Nocoldorwarmpacks• Noultrasoundtherapy• NoNSAIDS
• 8weekswithMSCorPRP/MSC• 2weekswithPRPtx
Copyright2017
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WhattechniquesdoIuse?
• Alloftheoneswejustmentioned!
• Iadjusttomypatient’sneeds,client’sneeds/wants
• IofferwhatIwoulddoifitwasmypet!
Evenmoreoptions
• Botulinumtoxin• Monoclonalantibodyfornervegrowthfactor– dogsANDcats• Undenatured TypeIICollagen• RadiationTherapy
Summary
• Treatearly– beproactive,notreactive• Don’twaituntilseverecartilagedamage• Weightlossandexercisearecrucialinallstages• Multimodalapproach• Includepainmanagement
UpdatedGuidelines
• https://www.aaha.org/public_documents/professional/guidelines/2015_aaha_aafp_pain_management_guidelines_for_dogs_and_cats.pdf
Thankyou ContactInfo
• Email:[email protected]• DrBrunke.wordpress.com• Cell(notforclients)518-470-7586• Office:VOSM– VeterinaryOrthopedicsandSportsMedicine• VOSM.com
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