Complications aiguës et chroniques liées aux nouveaux produits

H. Donnadieu-Rigole

Département d’addictologie

CHU Montpellier

Cet intervenant :

a déclaré ses liens d’intérêt

Tous les orateurs ont reçu une déclaration de liens d’intérêt.

Les NPS « New Psychoactive substances »

• Cathinones/Cannabis de synthèse/GHB/BZD/opiacés…

• 100 nouvelles substances /an

• Au moins 200 articles sur Pubmed de

janvier 2015 à avril 2016…

Plan

• Complications aigues somatiques

• Complications chroniques

• Complications liées au mode d’administration

Complications aiguesCathinones

Cannabis de synthèse

Synthetic Cathinones: A New Public Health Problem Current Neuropharmacology, 2015, Vol. 13, No. 1 13

Table 1. Molecular structure of the most spread synthetic cathinones.

Usual Names Equivalent Names Chemical Names Formula Structure

Butylone β-keto-N-

methylbenzodioxolylbutanamine,

bk-MBDB

1-(1,3-benzodioxol-5-yl)-2-

(methylamino)butan-1-one

C12H15NO3

Ethcathinone Ethylpropion, Eth-Cat (RS)-2-ethylamino-1-phenyl-

propan-1-one

C11H15NO

Ethylone 3,4-methylenedioxy-N-

ethylcathinone, MDEC,

bk-MDEA

(RS)-1-(1,3-benzodioxol-5-yl)-2-

(ethylamino)propan-1-one

C12H15NO3

3-Fluoromethcathinone 3-FMC (RS)-1-(3-Fluorophenyl)-2-

methylaminopropan-1-one

C10H12FNO

4-Fluoromethcathinone 4-FMC (RS)-1-(4-Fluorophenyl)-2-

methylaminopropan-1-one

C10H12FNO

Buphedrone α-methylamino-butyrophenone,

MABP

2-(methylamino)-1-phenylbutan-

1-one

C11H15NO

Mephedrone 4-methylmethcathinone, MMC,

4-MMC

(RS)-2-methylamino-1-

(4-methylphenyl)propan-1-one

C11H15NO

Methcathinone α-methylamino-propiophenone,

ephedrine, Cath, Jeff

(RS)-2-(methylamino)-1-phenyl-

propan-1-one

C10H13NO

Methedrone para-methoxymethcathinone,

4-methoxymethcathinone,

bk-PMMA, PMMC,

methoxyphedrine, meow meow

(RS)-1-(4-methoxyphenyl)-2-

(methylamino)propan-1-one

C11H15NO2

MDPV Methylenedioxypyrovalerone (RS)-1-(Benzo[d][1,3]

dioxol-5-yl)-2-(pyrrolidin-

1-yl)pentan-1-one

C16H21NO3

Methylone 3,4-

methylenedioxymethcathinone

(±)-2-Methylamino-1-

(3,4-methylenedioxyphenyl)

propan-1-one

C11H13NO3

Naphyrone Naphthylpyrovalerone, O-2482 (RS)-1-naphthalen-2-yl-2-

pyrrolidin-1-ylpentan-1-one

C19H23NO

Pentedrone 2-(methylamino)-1-

phenylpentan-1-one,

α-methylamino-valerophenone

(±)-1-phenyl-2-

(methylamino)pentan-1-one

C12H17NO

Pyrovalerone Centroton, 4-methyl-β-ketone-

prolintane, Thymergix, O-2371

(RS)-1-(4-methylphenyl)-2-

(1-pyrrolidinyl)pentan-1-one

C16H23NO

Karila et al. 2015

Cathinones• Catha edulis (Yemen, XVIII)

• Effet psychostimulant (euphorie, hyperactivité)

• 1.2% chez les 12/34 ans aux US (Palamar et al. 2015)

• 5% en Europe (20% des 14/20 ans

au royaume Unis)

• Disparité en fonction des groupes

– Ingestion +++

– Injection

Cathinones: Aux urgences….

CœurAbdomenPsy

Autres complications

Hyponatrémie/Rhabdomyolyse

Hyponatrémié sévère avec épilepsie après LSD •SIADH (Médié par le système serotoninergique)•Rabdomyolyse

ReinionogrammeMuscles…

Et aussi….

• Hyper ou hypothermie/ en fonction de l’environnement thermique

• Cystites amicrobiennes destructrices

Cannabis de synthèse

• Plus d’affinité pour les récepteurs CB1

• Pas de tabac ou de THC

• <1% en population générale

• 4000 cas dans la littérature: 26 décès

– Effets psychiatriques

– Effets indésirables

– sympathomimétiques

– hallucinogènes

Karila et al. 2016 Tait et al. 2015

Cardio-vasculairesTachycardieDouleurs thoraciquesIDMArrêt cardio-respiratoireIschémies cérébrales et hémorragies

Toujours y penser chez le jeune:Accident cardio-vasculaireInsuffisance rénale

Insuffisance rénale grave voire terminaleRhabdomyolyse

Epilepsie

Troubles digestifs

Atteinte Uro-néphrologique

« Cystite amicrobienne ? (Chu et coll., 2009)

«Destruction app. urinaire inférieur» Kétamine «chronique»

Hydronéphrose bilatérale

Risque de diabète ?(Wong, 2012)

Dans l’avenir, quel risque d’insuffisance rénale terminale ?????

Phénacétine (produit de coupe) IV avec cocaïne IV

‘’

sniff

Messages

Toujours y penser

• Assurer les fonctions vitales– USI

– Remplissage

– BZD

– Traitements symptomatiques

Pièges

• Produit annoncé comme consommé par l’usager

• Associations fréquentes de différents produits– Alcool

– Cocaïne

– Sildenafil

– Produits de coupe

COMPLICATIONS CHRONIQUES

La dépendance

– Craving

– phénomène de tolérance aigue

– Un syndrome de sevrage (tremblements, frissons, hypothermie)

– Affaissement des relations sociales

– Impact sur la libido

Transmission hépatite C et B=Injection de NPS

HCV

• Usage de drogue par voie IV – Plus gros pourvoyeur de

transmission

– 10 millions dans le monde

– 40 à 80% de séroprévalence en fonction des pays

HBV

• 5 à 10 % de séroprévalence suivant les pays

• Ag HBS (0.3 à 2.7 millions)

The epidemiology of viral hepatitis among people who inject

drugs: Results of global systematic reviews

Paul Nelson, Bradley Mathers, Benjamin Cowie, Holly Hagan, Don Des Jarlais, Danielle

Horyniak, and Louisa Degenhardt

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW,

Australia (P K Nelson MHSc, B M Mathers MBChB); Victorian Infectious Diseases Reference

Laboratory, North Melbourne, VIC, Australia (B Cowie PhD); College of Nursing, New York

University, New York, NY, USA (H Hagan PhD); Beth Israel Medical Center, New York, NY, USA

(Prof D Des Jarlais PhD); Centre for Population Health, Burnet Institute, Melbourne, VIC,

Australia (D Horyniak BBioMedSci, Prof L Degenhardt PhD); and Centre for Health Policy,

Programs and Economics, School of Population Health, University of Melbourne, Melbourne, VIC,

Australia (L Degenhardt)

Abstract

Background—Injecting drug use (IDU) is an important risk for viral hepatitis transmission.

Detailed, transparent estimates of the scale of the problem at regional and global levels have never

been made. We report national, regional and global prevalence and population size estimates for

hepatitis C (HCV) and hepatitis B (HBV) among people who inject drugs.

Methods—Systematic search of peer-reviewed (Medline/Embase/PsycINFO) and grey literature

databases, conference abstracts and online resources, with a widely distributed call for additional

data. From 4386 peer-reviewed and 1019 grey literature sources, 1125 were reviewed in full.

Studies were extracted to a customised database and graded according their methods. Serological

reports of HCV antibodies/anti-HCV, HBV antibodies/anti-HBc, and/or HBV surface antigen/

HBsAg among IDUs samples with n>40 participants, <100% HIV-positive, and sampling frames

that did not exclude participants on the basis of age or sex were included. Using endorsed decision

rules, prevalence estimates were calculated with anti-HCV and anti-HBV as proxies for exposure

and HBsAg for current infection. These were combined with IDU population sizes to estimate the

number of HBV and HCV positive IDUs.

Findings—Eligible reports of anti-HCV among IDUs were located for 77 countries. Prevalence

was 60–80% in 26 countries and >80% in 12. We estimate worldwide about 10.0 million (range

6.0–15.2M) IDUs might be anti-HCV positive. China, (1.6M), the USA (1.5M) and the Russian

Correspondence to: Prof Louisa Degenhardt, Centre for Population Health, Burnet Institute, 85 Commercial Road, Melbourne, VIC3004, Australia, louisa@burnet.edu.au.

Contributions

PN & LD developed the overall methodology for use in the reviews. HH and DDJ developed the methodology and oversaw data

extraction for the HCV Synthesis Project, and provided this for use in this review. DH maintained the customised database. PN & DH

conducted literature searches, extracted data and provisionally selected reports for use in generating estimates. PN & LD decided on

the final set of reports, with advice from BC; these were reviewed by HH, DDJ, DH & BM. BM developed the methodology and

generated regional and global estimates; these were reviewed by PN & LD. PN & LD led the writing of the manuscript; HH, DDJ,

DH, BC & BM commented and contributed text. PN generated the maps. All authors had access to all data used in this review. All

authors gave approval for the manuscript to be submitted.

Conflicts of interest

LD and BM have received grant money and have acted as independent consultants to the World Health Organization, UNAIDS and

the United Nations Office on Drugs and Crime. DDJ has been funded by, and acted as a consultant to, the WHO. LD received an

untied educational grant (2006–2008) from Reckitt Benckiser to conduct a post-marketing surveillance study of buprenorphine-

naloxone in the treatment of heroin dependence in Australia.

NIH Public AccessAuthor ManuscriptLancet. Author manuscript; available in PMC 2012 August 13.

Published in final edited form as:

Lancet. 2011 August 13; 378(9791): 571–583. doi:10.1016/S0140-6736(11)61097-0.

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The epidemiology of viral hepatitis among people who inject

drugs: Results of global systematic reviews

Paul Nelson, Bradley Mathers, Benjamin Cowie, Holly Hagan, Don Des Jarlais, Danielle

Horyniak, and Louisa Degenhardt

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW,

Australia (P K Nelson MHSc, B M Mathers MBChB); Victorian Infectious Diseases Reference

Laboratory, North Melbourne, VIC, Australia (B Cowie PhD); College of Nursing, New York

University, New York, NY, USA (H Hagan PhD); Beth Israel Medical Center, New York, NY, USA

(Prof D Des Jarlais PhD); Centre for Population Health, Burnet Institute, Melbourne, VIC,

Australia (D Horyniak BBioMedSci, Prof L Degenhardt PhD); and Centre for Health Policy,

Programs and Economics, School of Population Health, University of Melbourne, Melbourne, VIC,

Australia (L Degenhardt)

Abstract

Background—Injecting drug use (IDU) is an important risk for viral hepatitis transmission.

Detailed, transparent estimates of the scale of the problem at regional and global levels have never

been made. We report national, regional and global prevalence and population size estimates for

hepatitis C (HCV) and hepatitis B (HBV) among people who inject drugs.

Methods—Systematic search of peer-reviewed (Medline/Embase/PsycINFO) and grey literature

databases, conference abstracts and online resources, with a widely distributed call for additional

data. From 4386 peer-reviewed and 1019 grey literature sources, 1125 were reviewed in full.

Studies were extracted to a customised database and graded according their methods. Serological

reports of HCV antibodies/anti-HCV, HBV antibodies/anti-HBc, and/or HBV surface antigen/

HBsAg among IDUs samples with n>40 participants, <100% HIV-positive, and sampling frames

that did not exclude participants on the basis of age or sex were included. Using endorsed decision

rules, prevalence estimates were calculated with anti-HCV and anti-HBV as proxies for exposure

and HBsAg for current infection. These were combined with IDU population sizes to estimate the

number of HBV and HCV positive IDUs.

Findings—Eligible reports of anti-HCV among IDUs were located for 77 countries. Prevalence

was 60–80% in 26 countries and >80% in 12. We estimate worldwide about 10.0 million (range

6.0–15.2M) IDUs might be anti-HCV positive. China, (1.6M), the USA (1.5M) and the Russian

Correspondence to: Prof Louisa Degenhardt, Centre for Population Health, Burnet Institute, 85 Commercial Road, Melbourne, VIC3004, Australia, louisa@burnet.edu.au.

Contributions

PN & LD developed the overall methodology for use in the reviews. HH and DDJ developed the methodology and oversaw data

extraction for the HCV Synthesis Project, and provided this for use in this review. DH maintained the customised database. PN & DH

conducted literature searches, extracted data and provisionally selected reports for use in generating estimates. PN & LD decided on

the final set of reports, with advice from BC; these were reviewed by HH, DDJ, DH & BM. BM developed the methodology and

generated regional and global estimates; these were reviewed by PN & LD. PN & LD led the writing of the manuscript; HH, DDJ,

DH, BC & BM commented and contributed text. PN generated the maps. All authors had access to all data used in this review. All

authors gave approval for the manuscript to be submitted.

Conflicts of interest

LD and BM have received grant money and have acted as independent consultants to the World Health Organization, UNAIDS and

the United Nations Office on Drugs and Crime. DDJ has been funded by, and acted as a consultant to, the WHO. LD received an

untied educational grant (2006–2008) from Reckitt Benckiser to conduct a post-marketing surveillance study of buprenorphine-

naloxone in the treatment of heroin dependence in Australia.

NIH Public AccessAuthor ManuscriptLancet. Author manuscript; available in PMC 2012 August 13.

Published in final edited form as:

Lancet. 2011 August 13; 378(9791): 571–583. doi:10.1016/S0140-6736(11)61097-0.

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Priorité pour le traitement anti HCV

Transmission HIV

Risque augmenté

• HSH

• Augmentation du risque si injection cathinones (Giese et

al.2015)

– Irlande

– Roumanie

– Grèce

Prévention

• Echanges de seringues

• Salles d’injections sécurisées

• ETP autour de la réduction des risques

(MacArthur et al. 2014)

Cannabis de synthèse

• Altération des fonctions cognitives (Bossong et al.

2010) , Cancers

• Augmentation du risque d’usage problématique du cannabis de synthèse (Blevins

et al. 2016)

– Augmentation de conséquences psycho-sociales

Complications liées au mode d’administration

Injections/Etude Montpelliéraine

55%

13%

10%

10%

3%3%

3%3%

Type of infectionsSkin and Soft tissueinfections

sepsis

endocarditis

spondylitis

meningitis

pulmonary abscess

candidemia

endocarditis +spondylitis+sepsis

medication42%

illicit substances

45%

both13%

Injected substances

Cocaine 8Mephedrone 2

Amphetamine 4

31 patients repérés ELSA (80% H)IV= 23ATCD d’infections dans 65% des casStaph>strepto>Candida (Peyriere et al. 2013)

Intérêt des déclarations Intérêt des ELSA

Les injections

• Bactériémie à Staph. Aureus

– Augmentation avec les NPS depuis 2013

– Augmentation des abcès pulmonaires

– Augmentation des endocardites

Staphylococcus aureusbacteraemia associated with injected newpsychoactive substances

D . J. GRI FFI TH 1* , C. L . M A CK I N TOSH 1A N D D . I N VERA RI TY 2

1Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK2Department of M icrobiology, Royal Infirmary of Edinburgh, UK

Received 4 July 2015; Final revision 14 October 2015; Accepted 14 October 2015;

first published online 9 November 2015

SUM M ARY

Injecting drug use is often associated with deep-seated infection. In Lothian in Scotland there has

been a recent increase in the use of injected new psychoactive substances (NPS). Patients who

have injected NPS have presented with Staphylococcus aureus bacteraemia (SAB) with life-

threatening complications. We describe a unique case-series of 14 episodes of SAB in ten

patients. Users of injected NPS had a significantly higher incidence of endocarditis and cavitating

pulmonary lesions (P < 0·05) compared to those who inject only opiates. Cases of SAB in people

who inject NPS have contributed to a significant rise in the overall incidence of SAB in people

who inject drugs (P < 0·05) which has in turn impacted on the ability of Lothian to meet national

targets for reducing the incidence of SAB.

Key words: Bloodstream infections, endocarditis, injecting drug use, pulmonary abscess

Staphylococcus aureus.

I NT RODUCT I ON

In recent yearstherehasbeen a rapid increasein theuse

of new psychoactive substances (NPS) by people who

inject drugs (PWID) in Scotland [1]. These includesev-

eral different classesof active ingredient, including syn-

thetic cannabinoids and synthetic cathinones [2].

Although some of these substances have been made il-

legal in certain jurisdictions, there remains a wide var-

iety of subtly altered variants that have not yet been

legislated against and have indeed been manufactured

deliberately to circumvent existing laws [3]. Prior to

2009, NPS were not reported as a factor, causative or

not, in any deaths related to drugs in Scotland. Since

then there has been an increasing number seen, with

113 deaths in 2013 mentioning NPS as a factor [1].

NPS can be purchased in Scotland through many

routes, including directly from dealers, internet mar-

keting and retail outlets (‘head shops’). They have

been adopted by many PWID as alternatives to

more traditional drugs of misuse such as opiates

owing to their availability, legality, relatively low

cost and perceived safety [2, 4, 5].

Among PWID, some NPS are referred to as ‘bath

salts’ due to their visual similarity to bathing salts

[2, 4]. One such substance known as ‘Burst’ is a

NPS that was popular in the Lothian area of South

East Scotland during the study period [Scottish

Drugs Forum (SDF), personal communication], a

population of about 830 000 served by NHS Lothian

[6]. Although ‘bath salts’ typically contain synthetic

cathinones, related to an amphetamine analogue

derived from the plant Catha edulis (khat) [2, 4, 7],

the ingredients found in ‘Burst’ tend to be more vari-

able. During the period of this study, methioprop-

amine (MPA), butylone and ethylphenidate were

known to be in local circulation in ‘Burst’ (SDF,

* Author for correspondence: Dr D. J. Griffith, Regional InfectiousDiseases Unit, Western General Hospital, Crewe Road, EdinburghEH4 2XU, UK.(Email: davidgriffith2@nhs.net)

Epidemiol. Infect. (2016), 144, 1257–1266. © Cambridge University Press 2015

doi:10.1017/S095026881500271X

Epidemiol. Infect. (2016), 144, 1257–1266.

Parachutes ou « Body stuffing »

• Recherche d’effets prolongés = Effets retardés inattendus (Hendrickson et al. 2006)

• Methamphetamines dans un sachet (cavité corporelle) = effets secondaires majeurs

Le SLAM

• Augmentation du risque de transmission des MST

• Augmentation des hépatites C aigues

(Croi 2016, Abstract 675)

Réinfection VHC chez les HSH guéris

Dépistage de réinfection tous les 3-6 mois chez les HSH co-infectés

Martin TC, Grande-Bretagne, EASL 2016, Abs. PS006 actualisé

7,0

21,8

5,04 8,2

78,10

16,8

Vienne16,8/100 p-a

(8,7-32,3)54 patients

Paris21,8/100 p-a(11,3-41,8)41 patients

Traitement de l’hépatite C pour prévenir les nouvelles contaminations sur HSH VIH+

Martin NK, Royaume-Uni, EASL 2016, Abs. PS144 actualisé

Evolution de la prévalence et de l’incidence

Pour réduire l’incidence et la prévalence des infections chez les HSH, il faut associer traitement et éducation comportementale

Prévalence Incidence

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Pas de traitementhistorique

Référence Ttt par DAAà partir de 2015

Extension du tttpour tous les patients

Extension du ttt +éducation comportementale

Conclusion

• Toujours l’évoquer, le rechercher et le déclarer

• Suivi addictologique à préconiser

• Messages de prévention et d’information

Dominique A « vers le bleu »