TOXICOLOGICAL CHARACTERISTIC OF DESIGNER DRUGS FROM THE GROUP OF SYNTHETIC OPIOIDS

Capa

Citar

Texto integral

Resumo

Toxicological characteristic of designer drugs from the group of synthetic opioids is presented. The historical aspects of illicit drug trafficking are considered. In the illicit drug market of EU countries 38 synthetic opioids, 22 of them belonging to fentanyl derivatives, have been revealed for the period 2005-2017. The widespread use of synthetic opioids among drug addicts has been accompanied by an increase in the number of fatal overdoses. In the United States the number of fatal poisonings by synthetic opioids of fentanyl series increased by 40.3 times between 1999 and 2017. The similar situation is emerging in other countries. This is due to the fact that the biological activity and toxicity of synthetic opioids far exceed those of morphine and heroin. The differences between the metabolism of heroin and synthetic opioids are considered. Data on the toxicity of synthetic opioids are presented. The neurotransmitter mechanisms of their respiratory depression, including disorders of opioid, GABAergic, glutamatergic and serotoninergic neurotransmitter systems are discussed. A brief description of the antidote activity of opioid receptor antagonists in acute poisoning by synthetic opioids is given.

Sobre autores

A. Golovko

Institute of Toxicology of the Federal Medical and Biological Agency

Autor responsável pela correspondência
Email: prgolovko@inbox.ru

Golovko Aleksandr Ivanovich

192019, Saint Petersburg

Rússia

M. Ivanov

Institute of Toxicology of the Federal Medical and Biological Agency

Email: kkbk@bk.ru

Ivanov Maksim Borisovich

192019, Saint Petersburg

Rússia

V. Rejniuk

Institute of Toxicology of the Federal Medical and Biological Agency

Email: vladton@mail.ru

Rejniuk Vladimir Leonidovich

192019, Saint Petersburg

Rússia

Yu. Ivnitsky

Institute of Toxicology of the Federal Medical and Biological Agency

Email: neugierig@mail.ru

Ivnitsky Yurij Yur’evich

192019, Saint Petersburg

Rússia

V. Barinov

Institute of Toxicology of the Federal Medical and Biological Agency

Email: vladbar@front.ru

Barinov Vladimir Aleksandrovich

192019, Saint Petersburg

Rússia

V. Borodavko

Institute of Toxicology of the Federal Medical and Biological Agency

Email: institute@toxicology.ru

Borodavko Viktor Konstantinovich

192019, Saint Petersburg

Rússia

Bibliografia

  1. Головко А.И., Башарин В.А., Иванов М.Б., Баринов В.А., Бонитенко Е.Ю. Дизайнерские наркотики. Классификации, механизмы токсичности. Наркология. 2015; 8: 69–85.
  2. Designer drug (2018). Available at: https://en.wikipedia.org/wiki/Designer_drug (accessed 10 January 2019).
  3. The European Monitoring Centre for Drugs and Drug Addiction (2018). Available at: http://www.emcdda.europa.eu/emcdda-home-page_en (accessed 10 January 2019).
  4. United Nations Office on Drugs and Crime (2018). Available at: https://www.unodc.org/ (accessed 10 January 2019).
  5. EMCDDA–Europol 2017 Annual Report on the implementation of Council Decision 2005/387/JHA (2018). Available at: http://www.emcdda.europa.eu/publica-tions/implementation-reports/2017_en (accessed 10 January 2019).
  6. Cole J.B., Nelson L.S. Controversies and carfentanil: We have much to learn about the present state of opioid poisoning. Am. J. Emerg. Med. 2017; 35 (11): 1743–1745.
  7. Pichini S., Solimini R., Berretta P., Pacifici R., Busardò F.P. Acute intoxications and fatalities from illicit fentanyl and analogues: An update. Ther. Drug Monit. 2018; 40 (1): 38–51.
  8. Prekupec M.P., Mansky P.A., Baumann M.H. Misuse of novel synthetic opioids: A deadly new trend. J. Addict. Med. 2017; 11 (4): 256–265.
  9. Rudd R.A., Seth P., David F., Scholl L. Increases in drug and opioid-involved over- dose deaths - United States, 2010-2015. MMWR Morb. Mortal. Wkly Rep. 2016; 65 (5051): 1445–1452.
  10. Веселовская Н.В., Коваленко А.Е. Наркотики. Свойства, действие, фармакокинетика, метаболизм. М.: Триада-Х; 2000.
  11. Raffa R.B., Pergolizzi J.V. Jr., LeQuang J.A., Taylor R. Jr., NEMA Research Group., Colucci S., et al. The fentanyl family: A distinguished medical history tainted by abuse. J. Clin. Pharm. Ther. 2018; 43 (1): 154–158.
  12. Misailidi N., Papoutsis I., Nikolaou P., Dona A., Spiliopoulou C., Athanaselis S. Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil. Forensic Toxicol. 2018; 36 (1): 12–32.
  13. Misailidi N., Papoutsis I., Nikolaou P., Katselou M., Spiliopoulou C., Athanaselis S. Furanylfentanyl: another fentanyl analogue, another hazard for public health. Forensic Toxicol. 2018; 36 (1): 1–11.
  14. Ujváry I., Jorge R., Christie R., Le Ruez T., Danielsson H.V., Kronstrand R. et al. Acryloylfentanyl, a recently emerged new psychoactive substance: a comprehensive review. Forensic Toxicol. 2017; 35 (2): 232–243.
  15. Погосов А.В., Мустафетова П.К. Опийные наркомании: история учения, этнокультуральные аспекты, клиника, лечение. М.: Белые альвы; 1998.
  16. Katselou M., Papoutsis I., Nikolaou P., Spiliopoulou C., Athanaselis S. A “krokodil” emerges from the murky waters of addiction. Abuse trends of an old drug. Life Sci. 2014; 102 (2): 81–87.
  17. Logan B.K., Mohr A.L.A., Friscia M., Krotulski A.J., Papsun D.M., Kacinko S.L. et al. Reports of adverse events associated with use of novel psychoactive substances, 2013-2016: A review. J. Anal. Toxicol. 2017; 41 (7): 573–610.
  18. Fentanyl and its analogues - 50 years on (2017). Available at: https://www.unodc.org/documents/scientific/Global_SMART_Update_17_web.pdf (accessed 10 January 2019).
  19. Dhawan B.N., Cesselin F., Raghubir R., Reisine T., Bradley P.B., Portoghese P.S. et al. International Union of Pharmacology. XII. Classification of opioid receptors. Phar- macol. Rev. 1996; 48 (4): 567–592.
  20. Singh V.K., Bajpai K., Biswas S., Haq W., Khan M.Y., Mathur K.B. Molecular biol- ogy of opioid receptors: recent advances. Neuroimmunomodulation. 1997; 4 (5–6): 285–297.
  21. Dahan A., Aarts L., Smith T.W. Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology. 2010; 112 (1): 226–238.
  22. Davenport-Hines R. The pursuit of oblivion: A global history of narcotics. New York: W.W. Norton & Company, Inc.; 2003.
  23. History of heroin. UNODC (1953). Available at: https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1953-01-01_2_page004.html (accessed 10 January 2019).
  24. Payte J.T. A brief history of methadone in the treatment of opioid dependence: a personal perspective. J. Psychoactive Drugs. 1991; 23 (2): 103–107.
  25. Dole V.P., Nyswander M.E. Heroin addiction – a metabolic disease. Arch. Intern. Med. 1967; 120 (1): 19–24.
  26. Henderson G.L. Designer drugs: past history and future prospects. J. Forensic Sci. 1988; 33 (2): 569–575.
  27. Armenian P., Vo K.T., Barr-Walker J., Lynch K.L. Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review. Neuropharmacology. 2018; 134 (Pt A): 121–132.
  28. Recommended methods for the identification and analysis of fentanyl and its analogues in biological specimens. Manual for use by National drug analysis laboratories. UNODC (2017). Available at: https://www.unodc.org/documents/sci-entific/Recommended_methods_for_the_identification_and_analysis_of_Fentanyl.pdf (accessed 10 January 2019).
  29. Suzuki J., El-Haddad S. A review: Fentanyl and non-pharmaceutical fentanyls. Drug Alcohol Depend. 2017; 171: 107–116.
  30. Vadivelu N., Kai A.M., Kodumudi V., Sramcik J., Kaye A.D. The opioid crisis: a comprehensive overview. Curr. Pain Headache Rep. 2018; 22 (3): Article 16. 6 p. Available at: https://link.springer.com/article/10.1007%2Fs11916-018-0670-z (accessed 10 January 2019).
  31. Mounteney J., Giraudon I., Denissov G., Griffiths P. Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe. Int. J. Drug Policy. 2015; 26 (7): 626–631.
  32. Overdose death rates. National Institute on Drug Abuse (2018). Available at: https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates (accessed 10 January 2019).
  33. Hedegaard H., Warner M., Miniño A.M. Drug overdose deaths in the United States, 1999-2016. NCHS Data Brief. 2017; 294: 1–8.
  34. Hikin L., Smith P.R., Ringland E., Hudson S., Morley S.R. Multiple fatalities in the North of England associated with synthetic fentanyl analogue exposure: Detection and quantitation a case series from early 2017. Forensic Sci. Int. 2018; 282: 179–183.
  35. Salmon A.Y., Goren Z., Avissar Y., Soreq H. Human erythrocyte but not brain acetylcholinesterase hydrolyses heroin to morphine. Clin. Exp. Pharmacol. Physiol. 1999; 26 (8): 596–600.
  36. Christrup L.L. Morphine metabolites. Acta Anaesthesiol. Scand. 1997; 41 (1, Pt 2): 116–122.
  37. Piazza O., Cascone S., Sessa L., De Robertis E., Lamberti G. The effect of liver esterases and temperature on remifentanil degradation in vitro. Int. J. Pharm. 2016; 510 (1): 359–364.
  38. Stevenson G.W., Luginbuhl A., Dunbar C., LaVigne J., Dutra J., Atherton P. et al. The mixed-action delta/mu opioid agonist MMP-2200 does not produce conditioned place preference but does maintain drug self-administration in rats, and induces in vitro markers of tolerance and depen- dence. Pharmacol. Biochem. Behav. 2015; 132: 49–55.
  39. Zacny J.P., Lichtor J.L., Zaragoza J.G., de Wit H. Effects of fasting on responses to intravenous fentanyl in healthy volunteers. J. Subst. Abuse. 1992; 4 (2): 197–207.
  40. Coluzzi F., Bifulco F., Cuomo A., Dauri M., Leonardi C., Melotti R.M. et al. The challenge of perioperative pain manage- ment in opioid-tolerant patients. Ther. Clin. Risk Manag. 2017; 13: 1163–1173.
  41. Liu S.S., Wu C.L. Effect of postoper- ative analgesia on major postoperative complications: a systematic update of the evidence. Anesth. Analg. 2007; 104 (3): 689–702.
  42. Fentanyl: what is a lethal dosage? Oxford Treatment Center (2018). Available at: https://www.oxfordtreatment.com/fentanyl/lethal-dose/ (accessed 10 January 2019).
  43. Benarroch E.E. Endogenous opioid systems: current concepts and clinical correlations. Neurology. 2012; 79 (8): 807–814.
  44. Holden J.E., Jeong Y., Forrest J.M. The endogenous opioid system and clinical pain management. AACN Clin. Issues. 2005; 16 (3): 291–301.
  45. Cox B.M., Christie M.J., Devi L., Toll L., Traynor J.R. Challenges for opioid receptor nomenclature: IUPHAR Review 9. Br. J. Pharmacol. 2015; 172 (2): 317–323.
  46. Ren J., Ding X., Greer J.J. 5-HT1A recep- tor agonist Befiradol reduces fentanyl-in- duced respiratory depression, analgesia, and sedation in rats. Anesthesiology. 2015; 122 (2): 424–434.
  47. Dahan A., Yassen A., Bijl H., Romberg R., Sarton E., Teppema L. et al. Compari- son of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br. J. Anaesth. 2005; 94 (6): 825–834.
  48. Головко А.И., Бонитенко Е.Ю. Социально-экономические последствия употребления психоактивных веществ. Профилактическая и клиническая медицина. 2011; 2 (1): 60–71.
  49. Warner-Smith M., Lynskey M., Darke S., Hall W. Heroin overdose: Prevalence, correlates, consequences and interven- tions. National Drug and Alcohol Research Centre, University of New South Wales, Monograph № 46; 2000.
  50. White J.M., Irvine R.J. Future directions in opioid overdose. Addiction. 1999; 94 (7): 978–980.
  51. Funk G.D., Smith J.C., Feldman J.L. Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids. J. Neurophysiol. 1993; 70 (4): 1497–1515.
  52. Wasserman A.M., Ferreira M. Jr., Sahibzada N., Hernandez Y.M., Gillis R.A. GABA-mediated neurotransmission in the ventrolateral NTS plays a role in respiratory regulation in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002; 283 (6): R1423-R1441.
  53. Pasternak G.W. Multiple opiate recep- tors: déjá vu all over again. Neuropharma- cology. 2004; 47 (Suppl. 1): 312–323.
  54. Chen S.W., Maguire P.A., Davies M.F., Beatty M.F., Loew G.H. Evidence for μ1-opioid receptor involvement in fentan- yl-mediated respiratory depression. Eur. J. Pharmacol. 1996; 312 (2): 241–244.
  55. Chevillard L., Mégarbane B., Baud F.J., Risède P., Declèves X., Mager D. et al. Mechanisms of respiratory insufficiency induced by methadone overdose in rats. Addict. Biol. 2010; 15 (1): 62–80.
  56. Manzke T., Guenther U., Ponimaskin E.G., Haller M., Dutschmann M., Schwar- zacher S. et al. 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science. 2003; 301 (5630): 226–229.
  57. Ren J., Poon B.Y., Tang Y., Funk G.D., Greer J.J. Ampakines alleviate respiratory depression in rats. Am. J. Respir. Crit. Care Med. 2006; 174 (12): 1384–1391.
  58. Cumpston K.L., Wiggins J.C., Mlodz- inski S., Moyer J., Wills B.K. Update on current treatment of acute opioid overdose. Curr. Treat. Options Psych. 2018; 5 (3): 301–312.
  59. The history of naloxone (2017). Available at: http://cordantsolutions.com/the-history-of-naloxone/ (accessed 10 January 2019).
  60. Kaplan J.L., Marx J.A., Calabro J.J., Gin-Shaw S.L., Spiller J.D., Spivey W.L. et al. Double-blind, randomized study of nalmefene and naloxone in emergency de- partment patients with suspected narcotic overdose. Ann. Emerg. Med. 1999; 34 (1): 42–50.
  61. Sudakin D. Naltrexone: Not just for opioids anymore. J. Med. Toxicol. 2016; 12 (1): 71–75.
  62. Ingman K., Hagelberg N., Aalto S., Någren K., Juhakoski A., Karhuvaara S. et al. Prolonged central μ-opioid receptor occupancy after single and repeated nalmefene dosing. Neuro-psychopharmacology. 2005; 30 (12): 2245–2253.
  63. Wang D.S., Sternbach G., Varon J. Nalmefene: a long-acting opioid antagonist. Clinical applications in emer- gency medicine. J. Emerg. Med. 1998; 16 (3): 471–475.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Golovko A.I., Ivanov M.B., Rejniuk V.L., Ivnitsky Y.Y., Barinov V.A., Borodavko V.K., 2019


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 81728 от 11 декабря 2013.