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Introduksjon
Rusmidlerog
NyePsykoaktive Stoffer(NPS)
KnutErik Hovda
Overlege,PhD
Nasjonal behandlingstjene ste forCBRNemedisin
Akuttmedisinsk avd
Oslo universitetssykehus HF
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
• Bakgrunn og eksempler
• De“klassiske” narkotiske stoffene
• Denye psykoaktive stoffene – bakgrunn ogdefinisjon
– Grupper og eksempler
– Kjemiske formler
– Navngiving
– Kliniske utfordringer
• Sammendrag
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
http://www.youtube.com/watch?v=bXo-0iFj8Ys
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Narkotika &Motedop
¨ Narkotikahandel: 3.størstebudsjettiverden
IVest-Europa/USA ca1.5- 3.0%av BNP 1
¨ Største industrietter bilindustrien– ’tax-free’
¨ Nyere drogekultur
¡ Internasjonal
¡ Multimedial(Internett)
¡ Nysosialstatus
(’knarker’ vs.’partydoper’)
¡ Peroralt misbruk- ikkeIV
¡ Trusselmotungdomshelsen
1
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
De klassiske narkotiske stoffene
• Cannabis – mestbrukt
• Amfetaminer – amfetamin vs.metamfetamin
• Ecstasy – UKogSpaina dominerer. Varierende innhold..
• Kokain – nestvanligst iSør- ogVest-Europa.
• Heroin – står fordenstørste sykeligheten ogdødeligheten
UNDOC/EMCDDA
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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Variationin
predominant
stimulantdrug
usedacross
Europe
Kokain
• 25%avalleAMI18-45årforbundetmedkokainbruk (CA)
• Akutte koronarsyndrom somfølgeav:
– Coronar vasokonstriksjon
– Intracoronar trombose
– Akselerert aterosklerose
• EF oftetilnærmet normal,
vanligvisåpne coronarkar
vedangiografi
EMCDDA
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Kokain overdose - behandling
• BZD er’drugs of choice’
– Brytedenondesirkelentilkokainetstoksisitet,vedåstimulere
BZD/GABA-reseptorene
• Ekstern kjøling (max 15 min ved >42C)
• (Phentolamine mot persisterende HT& vasospasmer)
• Unngå β-blokkere: Øktα-stim kangihypertensive
kriser
Courtesy of
Bob Hoffman,
Bellevue Hospital,
Manhattan
• HvisNa-kanal blokkade (↑QRS): Gi hyperton NaHCO3
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Amfetamin, forts
Amfetamin
• Generell sympatikomimetisk effekt
– Tachycardierogtachyarrytmier
– ↑BT,førstogfremstsystoliskBT
• Andre komplekse effekter:
– Generellvasokonstriksjon
– Aktiveringavtrombocytter
– Myokard-ischemiogarytmier
– Intrakranielleblødninger
– Uttalthypoglykemi;
§ Tommeglykogenlagre1?
§ Øktinsulinutskillelse2?
• Symptomer:
– Betydeligøktaktivitetsnivå,øktsmerteterskel,hypertermi,
hypertensjon,tachykardi,”tallerkenpupiller”
– Motoriskuro;ukritisk,utagerendeatferd
– OBS! -kroniskemisbrukereoftelitesymptomer
-kontaminanter
• Behandling:
– Symptomatisk
– BZDognedkjølingstårsentralt
1 Bews herPD
et al.Studies ofthe hypoglycemic effect ofd-amphetamine inaggregated mice.
Biochem Pharmacol 1966;14(3): 197-204. 2 McMahon et al.Methamphetamine-ind uced
ins ulin releas e.Science1971; 174: 66-68.
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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Ecstasy - MDMA
Metamfetamin
• Megetenkeltåsyntetisere
• GirtroliglengreogmereuforiskeffektennD-amfetamin
• ”Ice”:99-100%rentmetamfetamin.Flyktignåroppvarmet–
inhalasjongirtilsvarende”rush” sommetamfetaminiv.
• ØkendemengdebrukogbeslagiNorge
• MortalitetirelativtantalliNorge:
metamfetamin:amfetamin:kokain=6:3:1 1
•
•
•
•
•
’Complexdrugwithmanyactions’
Blokkerer reopptak avdopaminogserotoninisynapseriCNS
Hemmer produksjonenavserotonin
Stimulerer sympatikus
The three Es:
– Energi
– Empati
– Eufori
1
SERAF rapporten 2010
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
ECSTASY- MEKANISMER
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Ecstasy – pas 2
•
•
•
•
•
•
LibergJPetal.TidsskrNorLægeforen1998;28:4384-7.
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
K21,toktablEpåparty; hyperaktiv, økende tilkramper
Gjentatte kramper ved innleggelse
BT170/100,p170.41˚C
DIC,rhabdomyolyse,akutt nyresvikt
Levertransplantert etter 4dager
Morsetter graft-rejeksjon etter 18dager
Henry JA et al. Lancet 1992; 340: 384-87
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Ecstasy – psykiske senvirkninger
• Senker serotoninnivået i
CNS
• Personlighetsendringer
• Schizofrene trekk
• Kognitivdysfunksjon
• Læreproblemer
• Nedsatt
oppmerksomhet
• Nedsatt hukommelse
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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NPS - Background and definition (I)
• Eithersyntetic,semi-synteticornaturallyoccuringsubstancesintended
toillicitapsychoactiveresponse,beingeitherstimulant,hallucinogenic,
sedative oracombination ofthese
• Thereare manychemicalsimilaritiesbetween‘legalhighs’ and
endogenousneurotransmitters,specificallyserotonin,norepinephrine
anddopamine1
NPS - Background and definition (II)
• Marketed as“notforhumanconsumption”,“plantfood”,“bath
salts” oreven “pondcleaner”
• Significant variability inthecontentsofnovelpsychoactive
substances 1,2,3
• Typicallyappearing insmallergroupsfirst(often clubbersetc)
→increasing #ofusers
• Information spread especiallythrough internet
• Severalclassesof‘legalhighs’ havebeenmodeledonexistingand
controlleddrugsofabusebecauseofeaseinsynthesizing(esp.
phenylethylamine(amphetamine),cocaine,phencyclidineand
tryptamineclasses). 1
1
2
1
GibbonsS.ClinicalToxicology(2012),50,15–24
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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RamseyJetal (2010).QJMed103:777–783
Davies Setal (2010)QJMed103:489–493
SpillerHAetal (2011)ClinToxicol(Phila)49:499–505
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
NPS - Bakgrunn ogdefinisjon (III)
Main groups ofnew psychoactive substances
• Vanligvisutføres ikke rutinemessig screening (blod- eller
urinprøver) ettersom detoftest ikke vilpåvirke denakutte
behandlingen
• Groupingcanbe donedifferent ways; usuallyaccordingtotheir
chemicalstructure or their clinicaleffect (hallucinogenic,
stimulantetc).
• Dramatisk økningitilgjengelighet ogbrukdesisteårene:20052011:164nyepsykoaktivestoffer bleformelt meldtinngjennom
systemet fortidligvarsling(EWS)1 , 2012:>70 1 nyestoffer,2013:
>80 1 nyestoffer.
1. Phenetylamines
2. Tryptamines
• De nyetrendene øker viktigheten avåkjenne toksisiteten til
forbindelsene ogderes raskt endrede panorama:
1 EMCDDA2012-2014
”What isreallyoutthere?”.
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
EMCDDA New groups 2015 ->
3. Piperazines
4. Cathinones
5. Syntetic cannabinoids
6. Other substances
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
1. Phenetylamines
EWS Update March 2015
Update2015– “Technicallist”
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Piperazines
Benzodiazepines
Arylamines
Tryptamines
Opioids
Phenethylamines
Others Synthetic
Cannabinoids
Synthetic cathinones
• BelowisthegroupingusedbyEMCDDA:
Synthetic cannabinoids
Phenethylamines
Other substances
Arylalkylamines
Cathinones
Opioids
Benzodiazepines
Tryptamines
Aminoindanes
Arylcyclohexylamines
Piperazines
Piperidines and pyrrolidines
Plants andextracts
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
• Effects: stimulant,entactogenic orhallucinogeniceffects
• The mostcommongroupuntil2010
• Examples: amphetamine, methamphetamine, PMA,PMMA,
MDMA, MBDB,MDEA, mescaline,2C-E,Benzofurans and
benzodifuranes (e.g. BromoDragonfly, benzofury)
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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Bromo-dragonFLY
Bromo-dragonFLY
• Syntetisk hallusinogenmedamfetaminliknende egenskaper;
Sterk effekt på5HT2A,betydelig stimulerende og
vasokonstringerende effekter
• Syntetisk hallusinogenmedamfetaminliknende egenskaper;
Sterk effekt på5HT2A,betydelig stimulerende og
vasokonstringerende effekter
• Inntasgjerne som“blotters”/papirlapper
• Inntasgjerne som“blotters”/papirlapper
• Typiskdose0,5-1,5mg
• Symptomdebut oftest 20-90min
• Typiskdose0,5-1,5mg
• Symptomdebut oftest 20-90min
• Varighet inntil1døgn,iblantmer
• Dødsfallrapportert iNorge,Sverige, Danmark,
FinlandogUSA
• Varighet inntil1døgn,iblantmer
• Dødsfallrapportert iNorge,Sverige, Danmark,
FinlandogUSA
Thorlacius K,Borna C, Pers onne M. Lekartidningen. 200;16(105): 1199-1200
Thorlacius K,Borna C, Pers onne M. Lekartidningen. 200;16(105): 1199-1200
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
PMMA (I)
PMMA (II)
• PMMA;Para-methoxy-methyl-amphetamine
• Suddenoutbreak inNorwayin2010,
classifiedasanarcotic inNovember2010
• WhyPMMA?
– Possiblybecauseofoneoftheprecursorsintheproductionof
amphetamine&metamphetaminebecameillegalinRussia1
• WhythishighmortalitywithPMMA?
– Oftensoldasecstasyoramphetamine,butwithasloweronsetof
symptoms.Usersoftenthinkitis”weakdrugs”andusemoreto
gaineffect.
• 20reported mortalities 1 +foundin10-20personsdrivingunder
the influenceduring
14months
Vevels tadMetal.ThePMMAepidemicinN orway.Comparisonoffatalandnon-fatal
intoxications .Forens ic SciInt.2012.10;219(1-3):151-7.
2Bones T,KRIPOS- NationalCriminalIn
vestigationS ervice.Personalcommunication
1
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Bønes T,KRIPOS- NationalCriminalInvestigationS ervice.
Pers onalcommunication
1
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
2. Tryptamines
3. Piperazines
• Effects: predominantly hallucinogeniceffects
• Examples: α-Methyltryptamine (AMT), dimethyltryptamine
(DMT), psilocin,psilocybin,LSD,4-OH-metyletyltryptamin (4-OHMET)
• Effects: stimulants
• Examples: 1(-3-chlorophenyl)-piperazine (mCPP),
1-benzylpiperazine (BZP),A2,TFMPP,Beans(Happy Popper)
• First-pass-metabolism intheliver throughMAO=> useofMAO-i
• BZP:Effects likeamphetamine &MDMA
mCPP:Lesssympatico-mimetic,serotonergic overstimulation
(anxiety, hyperthermia etc.)
• Noknownfatalities
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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4. Cathinones
• Effects: stimulants,oftenalsohallucinogeniceffects
• The secondmostcommongroup
• “Bathsalts” (US) or“plantfood” (Europe) often refers tothisgroup…
Mephedrone
• The firstcathinone tobeformallyrisk-assessed
• ThefirstreportonMephedrone(female18yrs)diedinStockholm
December2008 1.Sincethatappearantlyamongthemostfrequently
usednovelpsychoactivedruginvariousrecreationalsettings;
• A night-club study showing 53% last monthuse and41% use on the night
ofthe survey 2
• Examples: mephedrone,flefedron, efedron, methylone, methylene
dioxy-pyruvalone (MDPV), methcathinone
• Mephedrone; Effect on5HT2A asMDMAandD2asamphetamine.
Toxicity:Cardiovascular +thermoregulation
• Internet surveys fromUK clubbers: approx 40% lifetime-use in 20103, and
61% in 20114.
• Possibledecreasewithchangeinlegislation;possiblechangetowards
similarproducts(”researchchemicals”/”legalalternativesto
mephedrone”)
G us tavs s onD,EscherC.Lakartidningen.2009Oct21-27;106(43):2769-71.
W oodDMetal.QJM.2012:Oct;105(10):959-64.Epub2012 Jun19.
DickD,TorranceC.2010.‘Mixmagdrugssurvey’,Mixmag225:44–53.
W ins tockA.2011.‘The2011Mixmagdrugs survey’,Mixmag,March,pp.49–59.
1
2
3
4
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
5. Syntetic cannabinoids /T HC-a nal ogues /”S pi ce ”
• Effects: hallucinogenic,sedative anddepressant effects
(sometimes alsostimulantproperties)
• Higher affinity forthe CB1receptor comparedtoclassical
cannabinoids,lessaffinityforCBD
• Increasing fastest alongwiththecathinones– nowmost
common
• Examples: JWH-011,JWH-018,JWH-019,JWH-122, JWH-133,
JWH-250,JWH-251, Remix,Space Station,RainbowinHeaven,
BlackWidow,DoubleDutch,Jamaican Spirit,Jamaican Potpurri,
DJ,BonzaiCitrus,XXXL,Package 69,AromaticPotpurri
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
6. Other substances
• Effects: Large variations; dependingonthesubstance
• Examples: plantderived andsyntetic psycoactive substances
(indanes(e.g. MDAI),narcotic analgetics, synthetic cocaine
derivatives, ketamine- andphencyclidinederivatives), and
medicinalproducts
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
GHB/GBL – where do we place them?
The typical clinical features…
• Originallydeveloped asananesthetic inthe60´s
• Used asarecreational drugforat least three decades
Stimulants
“uppers”
• Very easy tomake fromeasily available ingredients
• Stable, high-frequency useinmanycountries;
• Example - Norway;
– ↑ number ofseizures (relatively & total), but small part of thetotal
number of seizures
– Oslo; 5th most commonmain agentfor all tox.hospitalizations in 20031
and 20082
• Withdrawalscanbesevere
Depressants
“downers”
Other substances
Other substances
Piperazines
Spices
Cathinones
Phenetylamines
Other substances
– BZDdrugofchoice.Baclofen,propofol&barbiturates
Tryptamines
HovdaKEetal.Clin Tox 2008:46;35-41
LundCetal.BMCPublicHealth.2012Oct 9;12:858.
Hallucinogenic
1
2
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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Nomenklatur (I)
• Initialene til oppfinneren
– JWH-071;John W. Huffman
• Stedet deble syntetisert:
– HU-210;Hebrew University, Jerusalem
• Kodenavn:
– APICA: N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide
– APINACA: N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide
• Navnfor åhjelpe markedsføringen
– APICA =“2NE1” =jenteband fraSør-Korea
– APINACA =“AKB-48” =Populært japansk jenteband
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Euro-DEN
Takktil
Fridtjof Heyerdahl
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
Knut Erik Hovda - Trinn II,s pl OU S,mars 2016
Conclusion
• Trends inEurope;
– Increasingnumberofsubstances;difficulttokeepup
– Increasing#ofreportsonseveretoxicityandmortalities
– Difficulttobe“aheadoftime”;howdowecollatedataregarding
Clinicaltoxicology?
– Effectsandside-effectsarehighlyvaryingandunpredictable
– Nationalvariations,butthenewrecreationaldrugsrespectno
borders
– Fast-trackvariationsinpanoramadependingonlegislation,
availabilityofsubstances/precursorsetc.
– Impuritiesmightcomposebiguser- anddiagnosticproblems
Knut Erik Hovda - Trinn II,s plOU S,mars 2016
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