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The Opioid Epidemic - Why, How, and What You Can Do

About It MichelleA.Fritsch,Pharm.D.,BCGP,BCACPMedsMASH,LLCRetirementWellnessStrategies

https://www.nichd.nih.gov/research/supported/opioids

Objectives

Identifyappropriateopioidprescribingtoincludedose,lengthoftherapy,anddosechangesovertimewhenappropriate.

Describewhathappensinthebrainthatdrivesaddiction,withdrawal,tolerance,dependence,andrecovery.

Demonstratewhenandhowtousenaloxonetosavealife.

Opioids

•  Before1800–painconsideredaconsequenceofaging,noregulationcocaineoropioids

•  HarrisonNarcoticControlActof1914–duetoheroinabuseandprescription-inducedmorphinedependence

•  1920’sto1950’s–peopleinpain,evencancerpain,encouragedtosaveopioidsforthefinalweeks–  Eraoflittleuseofopioidsandundertreatedpain–  Continuedto1980’s

•  1990’s–addressedunder-treatmentofpain•  1995–Painasthe5thvitalsign

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Timelineofepidemic•  2000TheJointCommissionStandardforPainManagement

–  Statemedicalboards–  DrugEnforcementAgency(DEA)

•  1995December– Oxycontin®–  From1997to2002grew670,000to6.2millionprescriptions

•  2007to2017Problemsmounting

PainTher.2018Jun;7(1):13–21

PainTher.2018Jun;7(1):13–21

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PrescriptionDrugMonitoringPrograms

•  ChesapeakeRegionalInformationSystemforourPatients(CRISP)– HealthInformationExchange– MarylandandDistrictofColumbia– Gettingtherightinformationtotherightplaceattherighttime

https://www.cdc.gov/drugoverdose/pdf/PDMP_Factsheet-a.pdf

OpioidEpidemicnewguielines

•  CDCGuidelinesforPrescribingOpioidsforChronicPain2016

•  https://www.cdc.gov/drugoverdose/pdf/Guidelines_Factsheet-a.pdf

•  https://www.cdc.gov/drugoverdose/pdf/Guideline_Infographic-a.pdf

https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fmmwr%2Fvolumes%2F65%2Frr%2Frr6501e1er.htm

ReducedManufacturing

•  JusticeDepartmentandDEAplan– Sixmostcommonlyabusedopioids-  oxycodone,hydrocodone,oxymorphone,hydromorphone,morphine,fentanyl

-  Decreasesmanufacturingquotasby10%in2019

•  PresidentTrump‘SafePrescribingPlan’– Cutopioidprescriptionfillsby1/3in3years

https://www.dea.gov/press-releases/2018/08/16/justice-department-dea-propose-significant-opioid-manufacturing-reduction

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FDA

https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm617908.htm

MorphineMilligramEquivalents(MME’s)

https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf

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AcutePain•  (StandardsadoptedbyChaseBrextonaftermuchresearch)•  Avoidopioidsifpossible•  Offerothermodalities(TENS,PT,Massage,acupuncture)•  Ifopiate-minimalamounts-<50MME/day(morphinemg

equivalents)andrelativelyshortduration.•  Recommendnomorethanaseven(7)daysupplyandcontinue

fornomorethana3monthterm.•  Clearlyreassesseffectivenessofmedregimen,ADLs,evaluationbyspecialtyproviders,overallcontinueneedofmedicationatcurrentdoseoratall,consideralternatives

•  Ifneedofcontinuation,reassesssymptoms,needforfurtherevaluation

•  Goalistoavoidprogressiontochronicpainanddependence•  Seechronicpainmanagementprotocolifprogressionneeded

•  AlwaysofferaBowelRegimen

ChronicPain•  Newpatient:Initialvisit

– Considernoopioidsonfirstvisitifnorecords,consideralternatives

– Needrecordspriortoconsidering– CheckCRISPbeforeprescribingopioidsanddocument

–  Ifnomedicalrecords,useclinicaljudgment

ChronicPain•  NewPatient:Secondvisit/Establishedpatient

–  Chronicpainpatient(onpainmeds3monthsormore)–  AutomaticExclusionfromProtocol

•  Contraindicationstoopioids–  IntolerableAdversereaction–  Untreatedaddiction–  Substantialriskforadverseevent

•  Toohighdose–  >90MME/day(morphinemgequivalents)

•  Multiple(>1)practicedismissals•  Getlabs:Urinetox,TSH,PHQ-9,CAGEQuestionnaire(assessriskandabusepotential)

–  Expectedoutcomes:Prescribe–  Ifunexpectedoutcome,ie.Positiveforillicitdrugsornegativefor

metabolitesofopioidpreviouslyprescribed•  Considerlevelofcomfortofprescribingorspecialtycare

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ConcomitantMeds

•  Avoidbenzodiazepines•  Possiblymoreoverdosewithlongacting(Oxycontin®data)

Stress

•  Howdoyouhandle:– Anger– Criticism– Unexpectedannoyances– Youfaildotosomethingontime– Sadness– Disappointment

HateandHealth

•  Grudges•  Blame•  Isolation•  Oppression•  Resentment•  Self-pity•  Rejection

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ADDICTION

Continuingtorepeatabehaviorthatyouknowisharmfultobothyourselfandothers,inspiteofnegativeconsequences.Addictionisalossofcontrol.

Whatareyouraddictions?

TERMS •  TOLERANCE – nerve transmitters in the body adapt

during chronic use; each doses last a shorter time, less effective over time

•  PHYSICAL DEPENDENCE – natural physiologic process – the body lets the med treat the pain; lets the drugs drive the neurotransmitters

•  WITHDRAWAL – body aches, insomnia, irritability, tachycardia, weakness, yawning, shivering, stomach symptoms (because the body is expecting the drug to drive)

•  ADDICTION – dysfunctional use for other than alleviating pain; use for a high or low

•  PSEUDOADDICTION – in patients with severe, unrelieved pain; looks like addiction because so afraid to experience withdrawal or breakthrough pain

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Neurotransmitters•  Chemicalmessengers•  Carryamessage•  Madeintheneuron•  Makeatargetrespond•  Somekeyexamples

–  Epinephrine(adrenaline)–actionsyoucancontrol–  Norepinephrine(noradrenaline)–actionsyoucan’tcontrol

–  Dopamine–(seenextslide)–  Glutamate–alsoexcitatory–  GABA

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Dopamine

•  Inthebraincontrols:– Movement(toolittledopamineinParkinson’sDisease)

– Emotion– Motivation– Pleasure

•  Manydrugsofabusedump2-10timesthenormalamountofdopamineinthebrain

Glutamate•  FoundinMSG–makesfoodtastegood•  ImpactedbyPCP,ketamine(SpecialK),dextromethorphan(DMcoughsyrup)

•  Stimulatesrewardsystem

•  Changesinthebrainovertimecanimpactcognitivefunction– Memory–  Clearthinking

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DrugsandEffects•  HeroinandMarijuana–neurotransmitterssimilartonaturalones–  Trickthebraintobelieverealneurotransmitters(especiallydopamine)

•  CocaineandMethamphetamine–dumplargeamountofneurotransmitters,especiallydopamine

•  (Wecantalkaboutotherdrugsasquestionscomeup)

TERMS •  TOLERANCE – nerve transmitters in the body adapt

during chronic use; each doses last a shorter time, less effective over time

•  PHYSICAL DEPENDENCE – natural physiologic process – the body lets the med treat the pain; lets the drugs drive the neurotransmitters

•  WITHDRAWAL – body aches, insomnia, irritability, tachycardia, weakness, yawning, shivering, stomach symptoms (because the body is expecting the drug to drive)

•  ADDICTION – dysfunctional use for other than alleviating pain; use for a high or low

•  PSEUDOADDICTION – in patients with severe, unrelieved pain; looks like addiction because so afraid to experience withdrawal or breakthrough pain

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YourBrain’sResponse

•  Lessdopaminereleased•  Fewerreceptors•  Controlthedopaminebylettinglessbeavailable

YouFeel

• DOWN…•  Youhavelessofthoseexcitatoryneurotransmitters.

•  Youfeel:–  Tired–  Edgy–  Lackofmotivation– Negative–  Lackofhappyfeelings

YouSeek

•  Moredrugtogetthehappy,excited,highfeelingsback

YOURBRAINresponds•  Stilltoomuch•  Makeless•  Shutdownthereceptors

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OverTime

•  Changesinhabits*•  Changesinthethoughtsyoudon’tcontrol•  Lossofmemory•  Slowed,unclearthinking•  Poordecisionmaking

•  *Withoutyouknowingit,certainplaces/events/situationscan yourdrugseeking

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Treatments

•  ForOpioidoverdose,includesheroin:– Naloxone(Narcan)–takesovertheopioidreceptorandremovestheopioid

•  SUDDENwithdrawal,shorttermonly

– Naltrexone(Vivitrol)–blockstheopiatereceptorsotakingopiates(narcotics,heroin)won’twork.

•  Mustbethroughwithdrawalbeforetaking•  Thosewhohavetriedtooutdoseitwithhigherdosesoftendie–stopbreathing

Treatments

– Buprenorphineandnaloxone(Suboxone)–provideasteadyamountoflong-termstimulationtotheopioid(mu)receptor

•  Givesthebrainthatsteadydoseofdopamine•  Graduallydecreaseitasthebraingraduallytakesovermakingitsowndopamine

Alcohol

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Options•  Disulfiram(Antabuse)–can’tprocessthealcoholsoyougetverysick/nauseated

•  Naltrexone(Vivitrol)–opioidantagonist;notsurewhyithelpswithalcohol–  IMinjectiononceamonth

•  Acamprosate(Campral)–threetimesaday–  InhibitsGABA

•  Seizuremedicines–dopamine,GABA,andglutamate–  Topiramate(Topamax,Trokendi)-offlabel– Gabapentin(Neurontin)

RECOVERY

Returntoaformerlyhealthystate

NewandFuture

https://www.wsj.com/articles/fentanyls-new-foe-a-quick-test-strip-that-can-prevent-overdoses-11546252200

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MedicalMarijuanainMaryland

Source:NationalInstituteonDrugAbuse;NationalInstitutesofHealth;U.S.DepartmentofHealthandHumanServices

Objectives1.Explorewhoiseligibletoobtainmedical

cannabis(marijuana).2.Outlinetheprocesstoreceiveanorderfor

medicalcannabis.3.Understandthevarioustypesofmedical

cannabisproductsavailableinMaryland.4.Listthethreecomponentsofthemedical

cannabismarketinMaryland.5.Describethenumberofdispensarylocationsin

Maryland.

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TheGOOD

TheBAD

Cannabis

TheUNKOWN

HistoryofCannabis

•  DocumentedinChineseliteraturebackto2700BC

•  Netherlandsbackto2459BC•  UsedinAyurvedicmedicinebackto1700BC•  1550BCEgyptianprescriptionfound•  500BCaGreekdescriptionofcannabissteambaths

MarijuanainMaryland•  2013billsignedformedicalmarijuanaprogram•  2014billpassedtodecriminalizepossessionof10gramsorless

•  September2015MarylandMedicalCannabisLawpassed

•  2016publicsmokingorpossessionofmarijuanaparaphernaliadecriminalized(civilinfractionwithfinevscriminalcharge)

•  2017billtoapproverecreationalmarijuanadidnotpass

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MedicalCannabisinMaryland

For Whom?

When?By Whom?

How?

PhotoSource:NationalInstitutesofHealth;U.S.DepartmentofHealthandHumanServices

MarylandMedicalCannabisCommission

•  MMCCdevelopspolicies,procedures,regulations

•  NamedinhonorofNatalieMLaprade– Mrs.LapradewasmotherofBaltimoreCityDelegateCherylGlenn.

– Mrs.Lapradediedofkidneycancer;DelegateGlennbelievesmedicalcannabiscouldhavebenefitedhermother.

http://mmcc.maryland.gov/Pages/home.aspx

MedicalCannabisinMaryland

•  Growers(14)•  Processors(12)•  Dispensers(77–willbeupto102)

– 2allowedperstatesenatevotingdistrict•  IndependentLaboratory

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MarylandMedicalCannabisProcess

•  http://mmcc.maryland.gov/Documents/Infographics/Patient_QuickRef.pdf

•  Allpartiescertified.•  Guidelinesaroundeachstep,communication,reporting,transport,packaging,andmore.

•  Mustusecertificationwithin120days.

Quantity

•  120gramscanbepossessedatatime•  36gramsofTHCinamonth

•  Medicalprovidercanoverridewithjustification

CannabissativaL.

•  Averycomplexplant– Atleast489compounds– 70cannabinoids

M.A.ElSohly,D.Slade/LifeSciences78(2005)539–548

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EndocannabinoidSystem

Memory

Sleep

Mood

Appetite

Pain

Immuneresponse

Lifecycles

Marijuana(THC)intheBrain

•  https://www.drugabuse.gov/videos/reward-circuit-how-brain-responds-to-marijuana

CannabisPhytocannabinoids•  Tetrahydrocannabinol(THC)–psychoactive–hasbeen

selectivelycultivatedformanyyears–  Mayhaveanti-inflammatory,analgesic,antispasticity,neuroprotective,reductioninintraocularpressureeffects

•  Cannabidiol(CBD)–fromcannabidiolicacid–  Mayhaveanti-nauseaeffects,perhapsothers

•  Cannabigerol(CBG)–  Mayhaveappetitestimulanteffects,perhapsothers

•  Cannabichromene(CBC)–  Mayhaveanti-inflammatory,analgesic,andantidepressanteffects

•  Cannabinol(CBN)–abyproductofcannabisdegredationNabiximol=CBD+THC

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indicasativa

Cannabis

Terpenoids•  Pinenes–foundinpine

– MayprotectthebrainfrommemoryeffectsofTHC;mayhaveantibiotic,anti-inflammatory,andantitumoreffects

•  Limonene–foundinlemonsandcitruspeels;increaseseffectsofTHCandCBD– Mayhaveantidepressant,anti-inflammatory,andantitumoreffects

•  Beta-myrcene–foundinhops;indica– Mayhaveantioxidant,musclerelaxant,analgesic,sedativemedicationenhancingeffects

CannabisTerpenoids•  Beta-carophyllene–foundinblackpepper,copaiba,cloves,hops– Mayhaveanti-inflammatoryeffects,internalandtopical

•  Terpinolene–foundinallspice,teatree,blackcurrantbuds,juniper;sativa– Mayhaveantibacterialandantitumoreffects

•  Ocimene–foundinsweetbasilandallspice– Mayhaveantibacterialeffects;saidtohave‘Goldilocks’effects–nottoosedatingorstimulating

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EntourageEffect(theory)

https://www.scientificamerican.com/article/some-of-the-parts-is-marijuana-rsquo-s-ldquo-entourage-effect-rdquo-scientifically-valid/

MarylandIndications•  Conditiondocumentedbyaphysicianwithwhomthe

patienthasabonafidephysician-patientrelationship:–  Chronicordebilitatingdiseaseormedicationconditionthatresultsinpatientadmissiontohospiceorpalliativecare

–  Cachexiaorwastingsyndrome–  Severeorchronicpain–  Severenausea–  Seizures–  Severeandpersistentmusclespasms–  Anyotherconditionthatissevereandresistanttoconventionalmedicine

•  Annualreviewofpetitionstoaddconditions

AllReportedIndicationsadolescence hyperemesis Huntington’s pediatrics sportsmed

Alzheimer’sdx chronicfatigue insomnia PTSD stress

ALS depression menopause pregnancy Tourette’s

anxiety diabetes Migraine/HA lactation Women’shealth

arthritis drugaddiction Multiplesclerosis

prevention

asthma fibromyalgia Nausea/vomiting

Restlesslegs acne

ADHD gastrointestinal neuropathy schizophrenia cancer

Autism gerontology osteoporosis seizures

autoimmune glaucoma pain sexualdysfunction

bipolar hepatitisC Palliativecare skin

cachexia HIV/AIDS Parkinson’s socialanxiety

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TherapeuticOptions

Pain

Opioids

NSAIDs

Spasticity

Antispasmodics

Musclerelaxants

Nausea

Anticholinergics

Ondansetron

TherapeuticDecisions

Knownrisks Unknown

risks

CannabisAdverseEffects

Firstuse/shortterm•  Tachycardia(rapidheartbeat)•  Drymouth•  Dizziness/lightheadedness

–  Impairedmotorcoordination•  Hypotension(lowblood

pressure)•  Red,irritatedeyes•  Coughing(ifsmoked)•  Shorttermmemorydecline•  Alteredjudgement

–  Paranoia/psychosis,especiallywithhighdosesofTHC

Long-term•  Alteredbrainfunction/

lowereducationalachievement(especiallywithuseinearlyadolescence)

•  Hyper-emesissyndrome•  Chronicbronchitis(if

smoked)•  Addiction(1in10?)

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Anxiety•  Benzodiazepines

– Alprazolam(Xanax®),lorazepam(Ativan®),diazepam(Valium®)

–  Canbeabused–  Similarissuestocannabis:

•  Memoryimpairment•  Slowerreflexes•  Lessalert•  Drivinghazard•  hypotension•  Hazardousincombinationwithopioids*•  Fallsrisk*

*Limiteddatawithcannabis

Benzodiazepines

https://www.nih.gov/news-events/news-releases/despite-risks-benzodiazepine-use-highest-older-people

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PainMeta-analysis

Chronicpain

Multiplesclerosisspasticity(extract>smoked)

Fibromyalgia

“Ourresultssuggestthatcannabidiolinterfereswithbrainrewardmechanismsresponsiblefortheexpressionoftheacutereinforcingpropertiesofopioids,thusindicatingthatcannabidiolmaybeclinicallyusefulinattenuatingtherewardingeffectsofopioids.”

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PregnancyandLactation

•  Limiteddata•  Potentialforbraindevelopment,weight,stillbirth,NICUadmission

https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm421168.htm#notapproved

Changeswithadvancedage

Bodychanges Cannabisimpact

Lessoverallprotein Highlyproteinbound(somorefreedrug)

Morebodyfat Veryfatloving–effectslastlonger

Decreasedkidneyfunction Effectslastlonger/accumulate

Changesinliverenzymes Effectslastlonger/accumulate

DrugInteractions

•  IncreaseeffectsofotherCNSdepressants– Alcohol– Benzodiazepines– Opioids– Musclerelaxants

•  Increaseeffectsofamphetamines(ADHD)•  Caninteractwithmedicationsforseizures,cancer,HIV,andothers

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CBDOilfromHemp

https://www.fda.gov/newsevents/publichealthfocus/ucm484109.htm

NewestCBDoilproducts

•  AnnouncedJune25•  Epidiolex(purifiedCBD)

– ForLennox-GastautandDravetsyndromes;age2+

PurifiedCBDoil

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611047.htm

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DiagnosticandStatisticalManualofMentalDisorders(DSM-5)

•  Cannabis-relateddisorders292.x,305.20,304.30

•  Includes:–  Induceddelirium–  Inducedpsychosis–  Inducedanxiety–  Intoxication– withdrawal

Hope

ScientificSkepticism

MedicalMarijuanaParody

•  https://www.youtube.com/watch?v=DVeas1dTCBc

•  BlindedbytheLightbyManfredMann’sEarthBand

•  ParodybyJamesMcCormack

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Patients

•  Registertobequalifyingpatientonline;includegovernmentissuedidentification

•  Age21orcaregiver– Caregiverscanhaveupto5clients

•  Patient/caregiverisissuedanidentificationcardwiththeiruniquepatientidentificationnumbergivenbytheCommission(optional?)

•  Useproductonlyforintendedperson;intendeduse

Providers•  SeekregistrationwiththeCommissionviaanapplication;2

yearcertification•  PhysicianlicensedinMarylandingoodstandingregistered

toprescribecontrolledsubstances•  Issueawrittencertification•  30daysatatime;cansubmitjustificationifprofessional

opinionpatientrequiresmorefor30days•  Patient-providerrelationshiptoincludeassessment

–  History–  Physicalexamination–  Reviewofsymptoms–  Anyotherpertinentmedicalinformation–  Approvedindication

•  Mustbeevaluatedinpersonatleastevery365days

DosageForms

NoEdiblesinMaryland

Smoke

Vaporize

Oils–Topicalororal

Suppository

Pessary

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MedicalCannabisinMaryland

•  Growers–selectstrains,providegrowingconditions,securitystandardsonpremises,controlpestswithoutpesticides

•  Processors–preparethedosageforms,packagetheproduct

•  Dispensers–display,aidinselection,sell,document,collectdata,deliveryoption–  2allowedperSenatevotingdistrict

•  IndependentLaboratory–analyzeseachlotforcomponentsofTHC,CBD,terpenes

Prosecution

•  13-3313•  Anyofthefollowingpersonsactinginaccordance…maynotbesubjecttoarrest,prosecution,oranyciviloradministrativepenalty…forthemedicaluseofcannabis:–  (7)Ahospital,medicalfacility,orhospiceprogramwhereaqualifyingpatientisreceivingtreatment.

ExampleResourceSites

•  Findingadispensary&certifiedprovier– http://mmcc.maryland.gov/Pages/dispensaries.aspx

– www.weedmaps.com

•  Reviewingavailableproduct– https://www.mpsbaltimore.com/

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THC

CBD

Cautions–Illegalmarijuana

Laced with

Fentanyl Synthetic =èmajor bleeding

KeyNumbersinMaryland

•  2distributorspervotingdistrict•  36gramspermonth•  120gramsinpossessionatonetime•  5patientspercaregiver•  2caregiversperpatient

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Resources

•  http://www.dsd.state.md.us/COMAR/subtitle_chapters/10_Chapters.aspx#Subtitle62

•  http://cannabissafetyinstitute.org/wp-content/uploads/2015/01/Standards-for-Cannabis-Testing-Laboratories.pdf

•  http://mmcc.maryland.gov/Documents/Subtitle%2033_Sept2015_Corrected.pdf

•  http://mmcc.maryland.gov/Pages/home.aspx