Molecular targets of immunotoxic action of drugs
https://doi.org/10.36946/0869-7922-2020-2-10-16
Abstract
The aim of the article is to generalize information on possible molecular targets that ensure the implementation of the immunotoxic effects of drugs for the subsequent improvement of the methodological apparatus of immunotoxicological studies of new drugs and assess the prospects of the development of new directions of immunopharmacology. The results of the information search for official data provided by manufacturers of medicines registered in the Russian Federation (guidelines for use, clinical recommendations, reports on biomedical and clinical research), as well as data from pharmacological monitoring of the safety of their use conducted by Roszdravnadzor of the Russian Federation are summarized.
Guidelines for the use of 524 current international non-patent medicines, covering a total of more than 5000 generics in various forms, releases and dosages, were analyzed. The object of the search was data on undesirable side effects of medicines related to the human immune system.
The analysis showed that the immunotoxic effect is described for 40,6% of 524 active pharmacological agents. Clinical and pathogenetic characteristics allowed us to identify several cluster groups that can be characterized as immunotoxic syndromes: allergic, immunosuppressive, lymphotropic, generalized cytokine reaction, reactivation of the immune response, and immune activation of oncogenesis. Molecular targets of immunotoxic action were determined based on the known mechanisms of action of the analyzed drugs.
About the Authors
E. B. Shustov
Institute of Toxicology of the Federal Medical Biological Agency
Russian Federation
Russian Federation
Shustov Evgeny Borisovich
192019, Saint Petersburg
A. E. Kim
S.M. Kirov Military Medical Academy, RF Ministry of Defence
Russian Federation
Russian Federation
Kim Alexey Evgenyevich
194044, Saint Petersburg
M. B Ivanov
Institute of Toxicology of the Federal Medical Biological Agency
Russian Federation
Russian Federation
Ivanov Maksim Borisovich
192019, Saint Petersburg
References
1. Vidal. Medicines in Russia. M.: Vidal Rus; 2018 (In Russian).
2. Karkishchenko N.N., Ujba V.V., Karkishchenko V.N., Shustov E.B., Kotenko K.V., Okovityj S.V. Essays in sports pharmacology. Vol. 2. Vectors of Pharmacoprotections. M., SPb.: Ajsing; 2014 (In Russian).
3. Kalinina N.M., Ketlinskij S.A., Okovityj S.V., Shulenin S.N. Diseases of the immune system. Diagnosis and pharmacotherapy. M.: EKSMO; 2008 (In Russian).
4. A.N. Mironov et al., eds. Guidelines for conducting trials of medicinal products. Vol. 1, 2. M.: «Grif i K», 2012 (In Russian).
5. Vidal. Medicines in Russia. M.: Vidal Rus; 2018 (In Russian).
6. Kucenko S.A. Fundamentals of toxicology. Vol. 4. Section 6.1 Immunotoxicity. SPb.: Nauka; 2003: 119-145 (In Russian).
7. S8. Studies of immunotoxicity of drugs intended for humans. Harmonized three-way guidance ICH. 2005. Available at: https://labmgmu.ru/prrs_order/doklinicheskie-issledovaniya-bezopasnosti-lekarstvennyh-sredstv (Accessed 01.04.2020) (In Russian).
8. Zabrodskij P.F., Mandych V.G. Immunotoxicology of xenobiotics. Saratov: SVIBHZ; 2007 (In Russian).
9. A.N. Mironov et al., eds. Guidelines for conducting trials of medicinal products. Vol. 1, 2. M.: «Grif i K», 2012 (In Russian).
10. Zemskov A.M. Promising approaches to assessing the immune status of a person. Laboratornoe delo. 1986; 9:544548 (In Russian).
11. S8. Studies of immunotoxicity of drugs intended for humans. Harmonized three-way guidance ICH. 2005. Available at: https://labmgmu.ru/prrs_order/doklinicheskie-issledovaniya-bezopasnosti-lekarstvennyh-sredstv (Accessed 01.04.2020) (In Russian).
12. Zemskov A.M. Promising approaches to assessing the immune status of a person. Laboratornoe delo. 1986; 9:544548 (In Russian).
13. Descotes J. Immunotoxicology of drugs and chemicals. Amsterdam New York Oxford: Elsiver; 1986.
14. Karkishchenko V.N., Karkishchenko N.N., Shustov E.B. The pharmacological basis of therapeutics. Thesaurus. M., SPb.: Ajsing; 2018: 288 (In Russian).
15. Karkishchenko V.N., Karkishchenko N.N., Shustov E.B. The pharmacological basis of therapeutics. Thesaurus. M., SPb.: Ajsing; 2018: 288 (In Russian).
16. Okovityj S.V. Clinical pharmacology of immunostimulators. FarmIndeks-Praktik. 2003; 4: 104–149 (In Russian).
17. Kozlov V.K., Shustov E.B., Simbircev A.S. i dr. Basics of immunotoxicology. Vol. 1. General immunotoxicology. Immunotoxicity of chemical compounds. Immunopathological conditions and diseases initiated by toxicants. M.: Kommentaryi; 2019 (In Russian).
18. Okovityj S.V. Clinical pharmacology of immunostimulators. FarmIndeks-Praktik. 2003; 4: 104–149 (In Russian).
19. Kalinina N.M., Ketlinskij S.A., Okovityj S.V., Shulenin S.N. Diseases of the immune system. Diagnosis and pharmacotherapy. M.: EKSMO; 2008 (In Russian).
20. Vidal. Medicines in Russia. M.: Vidal Rus; 2018 (In Russian).
21. A.N. Mironov et al., eds. Guidelines for conducting trials of medicinal products. Vol. 1, 2. M.: «Grif i K», 2012 (In Russian).
22. S8. Studies of immunotoxicity of drugs intended for humans. Harmonized three-way guidance ICH. 2005. Available at: https://labmgmu.ru/prrs_order/doklinicheskie-issledovaniya-bezopasnosti-lekarstvennyh-sredstv (Accessed 01.04.2020) (In Russian).
23. Zemskov A.M. Promising approaches to assessing the immune status of a person. Laboratornoe delo. 1986; 9:544548 (In Russian).
24. Karkishchenko V.N., Karkishchenko N.N., Shustov E.B. The pharmacological basis of therapeutics. Thesaurus. M., SPb.: Ajsing; 2018: 288 (In Russian).
25. Okovityj S.V. Clinical pharmacology of immunostimulators. FarmIndeks-Praktik. 2003; 4: 104–149 (In Russian).
Review
For citations:
Shustov E.B., Kim A.E., Ivanov M.B. Molecular targets of immunotoxic action of drugs. Toxicological Review. 2020;(2):11-17. (In Russ.) https://doi.org/10.36946/0869-7922-2020-2-10-16
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