Prospects for the development of inhalation drugs for the provision of pre-hospital assistance to affected by hazardous chemical substances


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Abstract

Abstract. Pharmacological agents are analyzed, in respect of which it is advisable to develop dosage forms for inhalation use as medical means of protection at the prehospital stage of medical evacuation in case of damage by emergency-hazardous chemicals. It was found that the inhalation intake of hazardous chemicals, especially with a pronounced pulmonotoxic, irritating and generally poisonous effect, is highly likely to develop post-intoxication complications associated with damage to the lung parenchyma, and death. For the therapy of such intoxications, it is advisable to administrate drugs in a dosage form for inhalation administration, which have several advantages: high bioavailability, rapid onset of effect, and severity of local action in various parts of tracheobronchial tree. The data of experimental and clinical studies of the effectiveness of drugs belonging to various pharmacological groups allow us to recommend for the further development of inhaled forms of means of prevention and treatment of toxic pulmonary edema (fluticasone, roflumilast, rolipram). Bronchodilators and donors of sulfhydryl groups (ipratropium bromide, tiotropium bromide, atropine sulfate, fenoterol, salbutamol, formoterol, unitiol dimercaprol) are referred to means of correction of respiratory disorders of various etiologies. Diazepam, midazolam, clonazepam, lorazepam are considered to be the most likely anticonvulsants from the enzodiazepine-class suitable for inhalation. Acetylcysteine, hydroxycobalamin can be used to combat hypoxia. The principal possibility of inhalation application of bioscavengers (acetylcholinesterase, butyrylcholinesterase) for the treatment of cholinopositive symptoms of toxic genesis is shown. Existing methods and means of delivery allow the use of these drugs at the prehospital stage of medical evacuation as part of single dose metered powder inhalers.

About the authors

I. M. Ivanov

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Author for correspondence.
Email: gniiivm_15@mail.ru
Russian Federation, Saint Petersburg

A. S. Nikiforov

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Email: gniiivm_15@mail.ru
Russian Federation, Saint Petersburg

M. A. Yudin

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation; North-Western State Medical University named after I.I. Mechnikov

Email: gniiivm_15@mail.ru
Russian Federation, Saint Petersburg; Saint Petersburg

A. M. Sventitskaya

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Email: gniiivm_15@mail.ru
Russian Federation, Saint Petersburg

V. S. Pavlova

The Saint - Petersburg scientific reseach institute of vaccines and serums and the enterprise for the production of bacterial preparations

Email: gniiivm_15@mail.ru
Russian Federation, Saint Petersburg

References

  1. Авдеев, С.Н. Новые возможности двойной бронходилатационной терапии у пациентов с хронической обструктивной болезнью легких / С.Н. Авдеев, Н.В. Трушенко // Терапевтический архив. – 2019. – № 3. – С. 76–85.
  2. Государственный доклад о состоянии защиты населения и территорий РФ от ЧС природного и техногенного характера в 2018 году. – М.: МЧС России; ФГУ ВНИИ ГОЧС (ФЦ), 2019. – С. 26–28.
  3. Гребенюк, А.Н. Методические рекомендации по оказанию медицинской помощи личному составу при поражении продуктами горения / А.Н. Гребенюк, В.А. Башарин. – М.: ГВМУ, 2011. – 32 с.
  4. Жиркова, Е.А. Ингаляционная травма / Е.А. Жиркова, Т.Г. Спиридонова, П.А. Брыгин // Журн. им. Н.В. Склифосовского «Неотложная медицинская помощь». – 2019. – Т. 8, № 2. – С. 166–174.
  5. Исаев, В.С. Аварийно химически опасные вещества / В.С. Исаев, В.А. Владимиров // Стратегия гражданской защиты: проблемы и исследования. – 2012. – С. 618–655.
  6. Колбасов, К.С. Экспериментальное обоснование комплексного лекарственного средства для ингаляционного применения при поражениях, вызванных пульмонотоксикантами: автореф. дис. … канд. биол. наук. – СПб.: ФГБУН ИТ ФМБА России, 2016. – 26 с.
  7. Кузубова, Н.А. Влияние различных вариантов терапии на сокращение бронхов крыс с моделированной обструктивной болезнью легких / Н.А. Кузубова [и др.] // Росс. физиол. журн. им. И.М. Сеченова. – 2014. – Т. 100, № 9. – С. 1049–1058.
  8. Кукес, В.Г. Клиническая фармакология / В.Г. Кукес. – М.: Гэотар- Медиа, 2006. – 938 с.
  9. Простакишин, Г.П. Клинические рекомендации по оказанию медицинской помощи пострадавшим при остром ингаляционном поражении токсическими веществами в чрезвычайных ситуациях: учеб. пособие / Г.П. Простакишин [и др.] // М.: Всеросс. центр медицины катастроф «Защита» Минздрава России, 2015. – С. 87–118.
  10. Рузанова, Э.А. Сравнительный анализ эффективности ингаляционного введения антиоксидантов и кромогликата натрия при отравлении крыс пульмонотоксикантами / Э.А. Рузанова, И.М. Драчкова, П.Г. Толкач // Medline.ru. – 2013. – Т. 14. – С. 241–254.
  11. Alkanaimsh, S. Transient expression of tetrameric recombinant human butyrylcholinesterase in nicotiana benthamiana / S. Alkanaimsh [et al.] // Front. Plant. Sci. – 2016. – № 7. – Р. 743.
  12. Daley-Yates, P.T. Inhaled corticosteroids: potency, dose equivalence and therapeutic index / P.T. Daley-Yates / Br. J. Clin. Pharmacol. – 2015. – Vol. 80, № 3. – Р. 372–380.
  13. Deutsch, C.J. The diagnosis and management of inhalation injury: An evidence based approach / C.J. Deutsch [et al.] // Burns. – 2018. – Vol. 44, № 5. – Р. 1040–1051.
  14. Dhir, A. Seizure protection by intrapulmonary delivery of midazolam in mice / A. Dhir, D. Zolkowska, M.A. Rogawski // Neuropharmacology. – 2013. – № 73. – Р. 425–431.
  15. Dolkart, O. Protective effects of rosuvastatin in a rat model of lung contusion: stimulation of the cyclooxygenase 2-prostaglandin E-2 pathway / O. Dolkart [et al.] // Surgery. – 2015. – Vol. 157, № 5. – Р. 944–953.
  16. Dries, D.J. Inhalation injury: epidemiology, pathology, treatment strategies / D.J. Dries, F.W. Endorf // Scand. J. Trauma Resusc. Emerg. Med. – 2013. – № 21. – Р. 1–15.
  17. Foncerrada, G. Inhalation Injury in the Burned Patient / G. Foncerrada [et al.] // Ann Plast Surg. – 2018. – Vol. 80, № 3. – Р. 98–105.
  18. Herbert, J. COPD and asthma therapeutics for supportive treatment in organophosphate poisoning / J. Herbert [et al.] // Clin Toxicol (Phila). – 2019. – Vol. 57, № 7. – Р. 644–651.
  19. Hoyle, G.W. Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation / G.W. Hoyle [et al.] //Toxicol Appl Pharmacol. – 2016. – № 298. – С. 9–18.
  20. Huynh Tuong, A. Emergency management of chlorine gas exposure – a systematic review / A. Huynh Tuong [et al.] // Clin Toxicol (Phila). – 2019. – Vol. 57, № 2. – Р. 77–98.
  21. Kondo, T. β2-аdrenoreceptor аgonist inhalation during ex vivo lung perfusion attenuates lung injury / T. Kondo [et al.] // Ann. Thorac. Surg. – 2015. – Vol. 100, № 2. – Р. 480–486.
  22. Letort, S. The first 2(IB), 3(IA)-heterodifunctionalized β-cyclodextrin derivatives as artificial enzymes / S. Letort [et al.] // Chem Commun (Camb). – 2015. – Vol. 51, № 13. – P. 2601–2604.
  23. Lockridge, О. Naturally occurring genetic variants of human acetylcholinesterase and butyrylcholinesterase and their potential impact on the risk of toxicity from cholinesterase inhibitors / О. Lockridge [et al.] // Chem. Res. Toxicol. – 2016. – №29. – Р. 1381–1392.
  24. Masson, P. Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning / P. Masson, F. Nachon // J. Neurochem. – 2017. – № 2. – Р. 26–40.
  25. McDonough, J.H. Comparison of the intramuscular, intranasal or sublingual routes of midazolam administration for the control of soman-induced seizures / J.H. McDonough [et al.] // Basic Clin Pharmacol Toxicol. – 2009. – Vol. 104, № 1. – Р. 27–34.
  26. Mula, M. The safety and tolerability of intranasal midazolam in epilepsy / M. Mula / Expert Rev Neurother. – 2014. – Vol. 14, № 7. – Р. 735–740.
  27. Rosenberg, Y.J. Pharmacokinetics and immunogenicity of a recombinant human butyrylcholinesterase bioscavenger in macaques following intravenous and pulmonary delivery / Y.J. Rosenberg [et al.] // Chem. Biol. Interact. – 2015. – № 242. – Р. 219–226.
  28. Yeo, S.H. Efficacy and safety of inhaled corticosteroids relative to fluticasone propionate: a systematic review of randomized controlled trials in asthma / S.H. Yeo [et al.] // Expert Rev. Respir. Med. – 2017. – Vol. 11, № 10. – Р. 763–778.

Copyright (c) 2020 Ivanov I.M., Nikiforov A.S., Yudin M.A., Sventitskaya A.M., Pavlova V.S.

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