Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 24, Art. 25 (pp. 348-359)    |    2023       

»

Experimental study of the effeciveness of inhalation use of atropine for the correction of rwspiratory disordes in case of poisoning with organophosphorus compounds

Ivanov I.M., Subbotina S.N., Alhutova I.M., Kolesnikov A.M.

Federal State Budgetary Institution ?State Research Testing Institute of Military Medicine? of the Ministry of Defense of the Russian Federation, St. Petersburg 195043, St Petersburg, st. Lesoparkovaya, 4

Brief summary

The article carried out an experimental study of the effectiveness of inhalation use of atropine as a means of correcting respiratory disorders caused by acute poisoning of rats with an organophosphorus compound. It has been shown that intramuscular administration of a toxicant at a dose LD16 causes significant changes in the external respiratory function of rats, manifested in a decrease in the minute volume of respiration, icrease in inhalation and exhalation, an increase in expiratory pauses and the development of bronchoconstriction. The duration of toxic effects is 240-360 minutes. Single intratracheal administration of atropine in doses of 0,26 and 0,86 mg/kg (3 and 10 mg per person) helps to reduce the severity of bronchospasm by 1,6-2,6 times compared with the control group. Therapeutic effects persist for two to three hours, depending on the dose of antidote administered. In this regard the expediency of repeated administration of atropine with an interval of 2 hours is shown. Double inhalation use of the antidote at a dose of 0,26 mg/kg in accordance with the proposed scheme allows completely stopping the manifestations of bronchoconstriction and preventing recurrence of respiratory disorders. It was found that the repeated use of atropine at a dose of 0,86 mg/kg is characterized by an increase in the toxic effect of organophosphorus compounds and is accompanied by an increase in the proportion of dead rats. The obtained results indicate the inadmissibility in doses exceeding 3 mg.


Key words

organophosphorus compounds; external respiratory function; atropine; effectiveness; inhalation use

Reference list

1. Eddleston M., Mohamed F., Davies J. Respiratory failure in acute organophosphorus pesticide self-poisoning. QJM: monthly journal of the Association of Physicians. 2006; 99: 513-522.


2. Ivanov I.M., Sybbotina S.N., Alhytova I.M., i dr. Mehanizmi naryshenii dihaniya pri otravleniyah fosfororganicheskimi soedineniyami i napravleniya korrekcii pri pomoshi bronhorasshiryaushih sredstv. Medlain.ry. 2022; 23: 185-200. URL: http://medline.ru/public/art/tom23/art12.html (Data obrasheniya 24.03.2023).


3. Kryajevskih A.A., Kryajevskih A.A., Sybbotina S.N., Sklyarova N.A. Vliyanie fosfororganicheskih soedinenii na fynkciu vneshnego dihaniya kris pri intratrahealnom i vnytrijelydochnom vvedenii. Formyli farmacii. 2021; 3 (2): 60-65.


4. Rezk P.E., Graham J.R., Moran T.S. Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs. Inhal Toxicol. 2007; 19: 291-302.


5. Lainee P., Robineau P., Guittin P. Mechanisms of pulmonary edema induced by an organophosphorus compound in anesthetized dogs. Fundam Appl Toxicol. 1991; 17: 177-185.


6. Gundavarapu, S., Zhuang J., Barrett E.G. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: effects of epinephrine and oxygen therapies. Toxicol Appl Pharmacol. 2014; 274: 200-208.


7. Hulse E.J., Davies J.O., Simpson A.J. Respiratory complications of organophosphorus nerve agent and insecticide poisoning. Implications for respiratory and critical care. Am J Respir Crit Care Med. 2014; 190(12): 1342-1354.


8. Kamat, S.R., Heera S., Potdar P.V. Bombay experience in intensive respiratory care over 6 years J. Postgrad. Med. 1989; 35: 123-134.


9. Wess J., Eglen R.M., Gautam D. Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov. 2007; 6: 721-733.


10. Takemura Y., Helms M.N., Eaton A.F. Cholinergic regulation of epithelial sodium channels in rat alveolar type 2 epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2013; 304: 428-437.


11. Segura P., Chávez J., Montaño L.M. Identification of mechanisms involved in the acute airway toxicity induced by parathion. Naunyn Schmiedebergs Arch Pharmacol. 1999; 360: 699-710.


12. Herbert J., Thiermann H., Worek F., Wille T. COPD and asthma therapeutics for supportive treatment in organophosphate poisoning. Clin Toxicol (Phila). 2019; 57(7): 644-651.


13. Orma P.S., Middleton R.K. Aerosolized atropine as an antidote to nerve gas. Ann Pharmacother. 1992; 26: 937-938.


14. Kehe C.R., Lasseter K.C., Miller N.C. Comparative absorption of atropine from a metered-dose inhaler and an intramuscular injection. Ther Drug Monit. 1992; 14: 132-134.


15. Corcoran T.E., Venkataramanan R., Hoffman R.M. Systemic delivery of atropine sulfate by the microdose dry-powder inhaler. J Aerosol Med Pulm Drug Deliv. 2013; 26(1): 46-55.


16. Rykovodstvo po eksperimentalnomy (doklinicheskomy) izycheniu novih farmakologicheskih veshestv / pod obsh. red. R.Y. Habrieva // Moskva: Izd-vo «Medicina», 2005.


17. Obshaya toksikologiya / pod red. Kyrlyandskogo B.A., Filova V.A. M.: «Medicina», 2002.


18. Frazer D.G., Reynolds J.S., Jackson M.C. Determining when enhanced pause (Penh) is sensitive to changes in specific airway resistance. Toxicol Environ Health. 2011; 74 (5): 287-295.


19. Soliev A.Y. Lechenie hronicheskogo kashlya i bronhialnoi astmi. Biologiya i integrativnaya medicina. 2017; 5: 47 56.