clinical toxicology: an update - cena · 2017-09-15 · clinical toxicology: an update ... , scra...

VICTORIANPOISONSINFORMATIONCENTREANDAUSTINHOSPITALCLINICALTOXICOLOGYSERVICE

Clinical Toxicology:An Update

Dr.ShaunGreene


Drug Abuse in Australasia


NPS: New (Novel) Psychoactive Substances

“….anewpsychoactivedrug,inpureformorinapreparationthatisnotscheduledundertheSingleConventiononNarcoticDrugsof1961ortheConventiononPsychoactiveSubstances1971,butthatmayposeathreattopublichealth…..”


Supply: Australian Seizures


• What’soutthere?

• Limiteddata:• Surveys

• Variableconsistencyofsupply

• PoisonInformationCentres

• EmergencyDepartmentpresentations

• Littleformalanalyticaldataunlessdeathoccurs

Epidemiology

www.erowid.org

What makes a good psychoactive?Noradrenaline

• Stimulant

Serotonin

Dopamine

• Empathogen /entactogen

• Hallucinogen

• Eurphoriant

New Psychoactive Substances: ClassesNoradrenaline 1.Phenethylamines

Serotonin

Dopamine 2.Piperazines

3.Tryptamines

New Psychoactive Drugs: ClassesNoradrenaline

Serotonin

Dopamine

4.Syntheticcannabinoids

5.Other


New Psychoactive Substances NPSidentifiedinnationallaboratories2009-2012


• Naturalmonoaminealkaloid/neuromodulator• Synthesised inCNSfromphenylalanine• Rapidlymetabolised:MAO-AandMAO-B

Phenethylamines

Phenethylamine


• Alpha-MethylPhenylethylamine

• α-carbonmethylgroupêMAOdegradationandé CNSpenetration

Phenethylamines

Phenethylamine Amphetamine(


• Substitutionoftheaminogroupé potencyandstimulatoryeffectsvianoradrenaline,butoftenê othereffects

Phenethylamines

Phenethylamine Methamphetamine (


• MDMA– “ecstasy”• Substitutionatposition4producesserotonergicor

“entactogenic”effects

Phenethylamines

Phenethylamine 3,4-Methylenedioxymethamphetamine

Phenethylamine

AmphetaminePhenethylamine

CathinonePhenethylamine

Phenethylamine Mephedrone


• 4-Methylmethcathinone(meowmeow,4MMC,MCAT,bubbles)• Tablets/powder- oral+intranasalmostcommonroutes

• Cathinonesinvitroinhibit:• Dopamineactivetransporter• Serotonintransporter• Noradrenalinetransporter

Mephedrone (4-MMC)

• Plantfood


• Euphoria• Stimulant+hallucinogenic• Elevatedmood• Appreciationofmusic

� Easytomanufacture

� Onset15-30minutes,effects last2-3hours

Effectssimilartocombinationofecstasy,cocaine+amphetamine

• Decreasedhostility• Increasedsexualfunc.• Improvedmentalfunc.• Empathogen

Mephedrone – The New Ecstasy

Mephedrone associated with over 125 UK deaths


PercentageofregularecstasyuserswhousedaNPSin2012

• Dimethyl

NPS in Australia

0 2 4 6 8 10 12 14 16

Salviadivinorum

MDPV

Methylone

Mephedrone

2C-B**

DMT*

Syntheticcannabinoids

*Dimethyltryptamine(DMT)**4-bromo-2,5-dimethoxy-phenethylamine(2C-B)


25i-NBOMe


• Benzodiazepines1st,2nd and3rd line……..

• Hyperthermia• Seizures

• Noroleforphenytoin• Don’tforgetthe[Na]

• Hypertension• Beta-blockersareassociatedwithincreasedmortality….………..butnotforthereasonspreviouslythought

Management


• Last,butnotleast:

• Ketamineuropathy

• Cannabisinducedhyper-emesis• Trydroperidol

Management

Structural Heterogeneity

THC

SerotoninJWH-18

Structural Homogeneity

THC

SCRA

CB Receptor Agonism

CB1

CB2

Cannabinoid Receptor Agonists


• Youngmales

• Effects:1-2hours

• Adverseeffects70%,only5%attendED

- ethanol,SCRAviabong,youngmalesBarrattMJetal.DrugandAlcoholReview2013

• SCRAusers– 2.5%attendedEDpastyear

Winstock Aetal.Psychopharmacol 2013

Presentation…....who?


• Systematicreview– 106citations>4000cases

• Youngmale 59-100%

• Tachycardia 37-77%

• Agitation 16-41%

• Nausea 13-94%

• Simplesupportivecare

• O2,IVfluid,benzodiazepines

• EDstay<than8hours

Taitetal.ClinicalToxicology2016

Presentation…....what?


• Literature:>4000cases,>50deaths

• Agitated,tachycardicyoungmale…...• N+V,diaphoresis,seizures,mydriasis,muscletwitching,

shortnessofbreath,injectedconjunctivae,HT,paranoia

• AMI,shock,acutekidneyinjury,ischemicstroke• Pulmonaryinfiltrates• QTprolongation,hypokalaemia,leucocytosis• Death

• YoungpersonwithAKIorunexpectedcriticalillness?• AskaboutSCRAuse

SCRA Toxicity


• Drugusesurvey:22000respondents

• RiskofEDattendance30xSCRAcomparedtocannabisexposure


Some Reading……..


Prescription Opioid Analgesics


Victoria 2013

0 100 200 300

Roadtoll

Prescriptiondrugs

60

70

80

90

100

110

120

130

140

2004 2006 2008 2010 2012 2014

Relativerateofd

eathcf.20

05

Two ma Neoplasm

CVS

RTA

Death Rate in Victoria as Percentage of 2005 Value:Neoplastic, CVS and RTA Deaths

60

70

80

90

100

110

120

130

140

2004 2006 2008 2010 2012 2014

Percen

tageof2

005ba

selin

evalue

Two ma

Death Rate in Victoria as Percentage of 2005 Value:Deliberate Self-Poisoning Deaths

60

70

80

90

100

110

120

130

140

2004 2006 2008 2010 2012 2014

Percen

tageof2

005ba

selin

evalue

Two ma

Death Rate in Victoria as Percentage of 2005 Value:Unintentional Poisoning Deaths

Road and Unintentional Pharmaceutical PoisoningDeaths. Victoria: 2005-2014

0

100

200

300

400

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Totaldeaths

Roaddeaths Unintentionalpharmaceuticalpoisoning

0

50

100

150

200

250

300

350

400

450

500

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Num

bero

fdeaths

Year

Meth,amphetamine,ecstasy

Cocaine

Benzodiazepines

Heroin

Oxycodone,morphine,codeine

Fentanyl,pethidine,tramadol

Cannabisandderivatives

All Overdose Deaths Australia:2004-2014

Single Drug Overdose Deaths in Victoria

% of total deaths

0 5 10 15 20 25 30 35 40 45 50

Citalopram

Quetiapine

Codeine

Allbenzodiazepines

Methamphetamine

Amitriptyline

Paracetamol

Oxycodone

Methadone

Alcohol

Heroin

Multi-Drug Overdose Deaths in Victoria

% of total deaths

0 5 10 15 20 25 30 35

Citalopram

Quetiapine

Codeine

Allbenzodiazepines

Methamphetamine

Amitriptyline

Paracetamol

Oxycodone

Methadone

Alcohol

Heroin

Tota

l dea

ths

0

5000

10000

15000

20000

25000

30000

35000

40000

All CVS Neoplasms RTA UnintentionalOD

Selected Causes of Death:Victoria 2014

Cause of death

Tota

l dea

ths

0

5000

10000

15000

20000

25000

30000

35000

40000


Aver

age

year

s of

life

lost

Selected Causes of Death:Victoria 2014

0

5

10

15

20

25

30

35

40


Cause of death

2008 2009 2010 2011 2012 2013 2014

Metro 275 302 297 286 321 331 436

Rural 131 148 176 181 249 245 326

Australia 406 450 473 467 570 576 762

0

100

200

300

400

500

600

700

800

900

Num

bero

fDeaths

Prescription Opioid Deaths Australia:2008-2014

• Menaged25-54years• Economicallydisadvantaged• Ruralpopulations• Psychiatricillness• Apasthistoryofsubstanceabuse

Rintouletal.2010

Who is at risk for prescription opioid harm, including death?


• Opioidrelatedhospitaladmissions• Callstocommunitysupportservices• IVdrugabuseofprescriptionopioids

Allhaveincreasedsignificantlypast15years

It’s Not Just Death

0

20

40

60

80

100

120

140

160

1992 1994 1996 1998 2000 2002 2004 2006

Opioid Prescribing – AustraliaNo.ofp

rescrip

tions(tho

usands)

Oxycodone

0

20

40

60

80

100

120

140

160

1992 1994 1996 1998 2000 2002 2004 2006

No.ofp

rescrip

tions(tho

usands)

Oxycodone

No.ofd

eaths

Opioid Prescribing – Australia


DiversionØ 110millionoxycodonetabletsprescribedannually

• 2/3ofthesearenotusedasprescribed

• 90%ofinjectedprescriptionopioidsareobtainedviadiversion

Oxycodone Prescribing: Austin ED

30prescriptionsperday

0

5

10

15

20

25

30

35

2004 201420042016

Opioids are good for pain…..• Littleevidenceforlong-termuseinnon-cancerpain

60%ofpatientsexperienceadverseeffects

0 20 40 60 80 100

Placebo

Opioids Opioids

Placebo

There is no clear evidence of an advantage in using opioid-based analgesics over non-opioid

analgesics in the treatment of non-cancer pain

SedationConstipationPruritusHyperalgesiaToleranceDependenceAddiction…..


Achieving a Balance

Treatingpain Minimisingharm• Patients• Others


National initiatives

Evidence based guidelines

Public education

Treatment

Access to pain specialists

Access to addiction specialists

Multi-disciplinary approach

Opioid substitution programs

Improved Rx of overdoses

Availability of naloxone

PreventionRationalise prescribing and Rx

Patient selection

Treatment plans / contracts

Alternative pain Rx strategies

Education

Prescribers / medical students

Patients

Reducing diversion

Data sharing / prescription tracking

Pharmaceutical / prescribing regulation

Law enforcement

Safe drug disposal

No Easy Solution


Supplyreduction:

Victorian Pharmaceutical Misuse Summit April 2014

RealtimeprescriptionmonitoringPrescribereducationPBSquantitiesLimitinghospitaldischargeamountsRegistrationwithonedoctorAlternativetherapyavailability/access


Harmreduction:

Victorian Pharmaceutical Misuse Summit April 2014

NeedleandSyringeProgramsCommunitynaloxoneprovision/OTCnaloxonePainspecialistsandprogramsRegularprescriberCPDPrescribingthresholdstotriggerRxescalationChangingformulations– gelcapsules/Targin®Communityeducationregardingdangers

Will opioids potentially cause harm?

• Substance misuse disorder

• Psychiatric illness: depression

• Sedative drug use

• OSA, respiratory disease

Does my patient understand opioid treatment?

• Only one part of the solution

• Rx is short term

• Adverse effects

• Addiction possible

• Store safely

Does my patient have a follow-up plan?

• LMO review

• Notify LMO

• Provide instructions:

• Verbal and written


• Areopioidsgoodforthispain?• Willopioidspotentiallycauseharm?• Doesmypatientunderstandopioidtreatment?• Doesmypatienthaveafollow-upplan?

A recommended approach:


Thank you for your attention…..

Questions?

clinical toxicology: an update - cena · 2017-09-15 · clinical toxicology: an update ... , scra...

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