Кардиотоксичные лекарственные средства при лечении COVID-19

Актуальность. Пандемия COVID-19 вызвана вирусом SARS-CoV-2. Кардиотоксичному потенциалу лекарственных средств, используемых при лечении COVID-19, уделяется недостаточное внимание.

Цель. Краткий отчёт о влиянии на сердечно-сосудистую систему организма наиболее распространённых препаратов при лечении COVID-19.

Обсуждение. Для лечения заболевания COVID-19 использовались разные лекарственные средства. Среди наиболее распространённых препаратов стоит выделить гидроксихлорохин, ремдесивир, фавипиравир, фторхинолоны, интерферон-α2b, глюкокортикоиды, молнупиравир и ритонавир/нирматрелвир. Большинство препаратов способны вызывать изменения со стороны сердечно-сосудистой системы, особенно изменение интервала QT.

Заключение. Врачи должны учитывать кардиотоксичный потенциал всех лекарственных средств, используемых при лечении COVID-19. Терапевты и врачи общей практики должны знать о сердечно-сосудистых рисках при ведении пациентов с COVID-19, а также диспансеризации населения.

1. Ji W., Wang W., Zhao X. et al. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol. 2020; 92 (4): 433–440. doi: 10.1002/jmv.25682.

2. Zmitrukevich A.S. Cardiovascular сhanges in COVID19. Acta Scientific Medical Sciences. 2022; 6 (Special Issue 2): 32–39. doi: https://doi.org/10.31080/ASMS.2022.S02.0007.

3. Elming H., Brendorp B., Køber L. et al. QTc interval in the assessment of cardiac risk. Card Electrophysiol Rev. 2002; 6 (3): 289–294. doi: 10.1023/A:1016345412555.

4. Romanelli F., Smith K.M., Hoven A.D. Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity. Curr Pharmaceutical Des. 2004; 10 (21): 2643–2648. doi: 10.2174/1381612043383791.

5. Ooi E.E., Chew J.S., Loh J.P., Chua R. In vitro inhibition of human influenza A virus replication by chloroquine. Virol J. 2006; 3 (1): 1–3. doi: 10.1186/1743-422X-3-39.

6. Vincent M.J., Bergeron E., Benjannet S. et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005; 2 (1): 1–0. doi: 10.1186/1743-422X-2-69.

7. Yao X., Ye F., Zhang M. et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; 71 (15): 732–739. doi: 10.1093/cid/ciaa237.

8. Giudicessi J.R., Noseworthy P.A., Friedman P.A., Ackerman M.J. Urgent guidance for navigating and circumventing the QTc-prolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19). Mayo Clin Proc. 2020; 95 (6): 1213–1221. doi: 10.1016/j.mayocp.2020.03.024.

9. Schrezenmeier E., Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020; 16 (3): 155–166. doi: 10.1038/s41584-020-0372-x.

10. Pani A., Lauriola M., Romandini A., Scaglione F. Macrolides and viral infections: focus on azithromycin in COVID-19 pathology. Int J Antimicrobial Agents. 2020; 56 (2): 106053. doi: 10.1016/j.ijantimicag.2020.106053.

11. Tönnesmann E., Kandolf R., Lewalter T. Chloroquine cardiomyopathy — a review of the literature. Immunopharmacol Immunotoxicol. 2013; 35 (3): 434–442. doi: 10.3109/08923973.2013.780078.

12. Radke J.B., Kingery J.M., Maakestad J., Krasowski M.D. Diagnostic pitfalls and laboratory test interference after hydroxychloroquine intoxication: a case report. Toxicol Rep. 2019; 6: 1040–1046. doi: 10.1016/j.toxrep.2019.10.006.

13. Chatre C., Roubille F., Vernhet H. et al. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Saf. 2018; 41 (10): 919–931. doi: 10.1007/s40264-018-0689-4.

14. Hsia B.C., Greige N., Quiroz J.A. et al. QT prolongation in a diverse, urban population of COVID-19 patients treated with hydroxychloroquine, chloroquine, or azithromycin. J Interv Card Electrophysiol. 2020; 59 (2): 337–345. doi: 10.1007/s10840-020-00822-x.

15. Gautret P., Lagier J.C., Parola P. et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrobial Agents. 2020; 56 (1): 105949. doi: 10.1016/j.ijantimicag.2020.105949.

16. Shah R.R. Chloroquine and hydroxychloroquine for COVID-19: Perspectives on their failure in repurposing. J Clin Pharm Ther. 2021; 46 (1): 17–27. doi: 10.1111/jcpt.13267.

17. Richter S., Parolin C., Palumbo M., Palù G. Antiviral properties of quinolone-based drugs. Curr Drug Targets-Infect Dis. 2004; 4 (2): 111–116. doi: 10.2174/1568005043340920.

18. Cui Q., Cheng H., Xiong R. et al. Identification of diaryl-quinoline compounds as entry inhibitors of Ebola virus. Viruses. 2018; 10 (12): 678. doi: 10.3390/v10120678.

19. Khan I.A., Siddiqui S., Rehmani S. et al. Fluoroquinolones inhibit HCV by targeting its helicase. Antiviral Ther. 2012; 17 (3): 467–476. doi: 10.3851/IMP1937.

20. Enoki Y., Ishima Y., Tanaka R. et al. Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury. PloS One. 2015; 10 (6): e0130248. doi: 10.1371/journal.pone.0130248.

21. Dalhoff A. Immunomodulatory activities of fluoroquinolones. Infection. 2005; 33 (2): 55–70. doi: 10.1007/s15010-005-8209-8.

22. Marciniec K., Beberok A., Pęcak P. et al. Ciprofloxacin and moxifloxacin could interact with SARS-CoV-2 protease: preliminary in silico analysis. Pharm Rep. 2020; 72 (6): 1553–1561. doi: 10.1007/s43440-020-00169-0.

23. Karampela I., Dalamaga M. Could respiratory fluoroquinolones, levofloxacin and moxifloxacin, prove to be beneficial as an adjunct treatment in COVID-19?. Arch Med Res. 2020; 51 (7): 741–742. doi: 10.1016/j.arcmed.2020.06.004.

24. Falagas M.E., Rafailidis P.I., Rosmarakis E.S. Arrhythmias associated with fluoroquinolone therapy. International J Antimicrob Agents. 2007; 29 (4): 374–379. doi: 10.1016/j.ijantimicag.2006.11.011.

25. Yu R., Li P. Computational and experimental studies on the inhibitory mechanism of hydroxychloroquine on hERG. Toxicology. 2021; 458: 152822. doi: 10.1016/j.tox.2021.152822.

26. Siegel D., Hui H.C., Doerffler E. et al. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo [2, 1-f][triazin-4-amino] adenine cnucleoside (GS-5734) for the treatment of ebola and emerging viruses. J Med Chem. 2017; 60 (5): 1648–1661. doi: 10.1021/acs.jmedchem.6b01594.

27. Choi S.W., Shin J.S., Park S.J. et al. Antiviral activity and safety of remdesivir against SARS-CoV-2 infection in human pluripotent stem cell-derived cardiomyocytes. Antiviral Res. 2020; 184: 104955. doi: 10.1016/j.antiviral.2020.104955.

28. Mulangu S., Dodd L.E., Davey Jr R.T. et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Eng J Med. 2019; 381 (24): 2293–2303. doi: 10.1056/NEJMoa1910993.

29. Rau C., Apostolidou S., Singer D. et al. Remdesivir, sinus bradycardia and therapeutic drug monitoring in children with severe COVID-19. The Pediatric Infectious Disease Journal. 2021; 40 (12): e528. doi: 10.1097/INF.0000000000003309.

30. Eleftheriou I., Liaska M., Krepis P. et al. Sinus bradycardia in children treated with remdesivir for COVID-19. Pediatr Infect Dis J. 2021; 40 (9): e356. doi: 10.1097/INF.0000000000003214.

31. Gupta A.K., Parker B.M., Priyadarshi V., Parker J. Cardiac adverse events with remdesivir in COVID-19 infection. Cureus. 2020; 12 (10). doi: 10.7759/cureus.11132.

32. Baranovich T., Wong S.S., Armstrong J. et al. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol. 2013; 87 (7): 3741–3751. doi: 10.1128/JVI.02346-12.

33. Shannon A., Selisko B., Le N.T. et al. Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase. BioRxiv. 2020 May 15. doi: 10.1101/2020.05.15.098731.

34. Руженцова Т. А., Чухляев П. В., Хавкина Д. А., и др. Эффективность и безопасность применения фавипиравира в комплексной терапии COVID-19 лёгкого и среднетяжёлого течения. Инфекционные болезни: Новости. Мнения. Обучение. 2020; 9: (4): 26–38. doi: https://doi.org/10.33029/2305-3496-2020-9-4-26-38.

35. Киселёв Ю.Ю., Матвеев А.В., Мирзаев К.Б., Сычёв Д.А. Мониторинг безопасности применения фавипиравира: управление рисками развития нежелательных лекарственных реакций в клинической практике. Качественная клиническая практика. 2020; Спецвыпуск S4: 115–119. doi: https://doi.org/10.37489/2588-0519-2020-S4-115-119.

36. Michaud V., Dow P., Al. Rihani S.B. et al. Risk assessment of drug-induced long QT syndrome for some COVID-19 repurposed drugs. Clin Transl Sci. 2021; 14 (1): 20–28. doi: 10.1111/cts.12882.

37. Chinello P., Petrosillo N., Pittalis S. et al. QTc interval prolongation during favipiravir therapy in an Ebolavirus-infected patient. Pl=LoS Negl Trop Dis. 2017; 11 (12): e0006034. doi: 10.1371/journal.pntd.0006034.

38. Kopecky-Bromberg S.A., Martínez-Sobrido L., Frieman M. et al. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol. 2007; 81 (2): 548–57. doi: 10.1128/JVI.01782-06.

39. Zhou Q., Chen V., Shannon C.P. et al. Interferon-α2b Treatment for COVID-19. Front Immunol. 2020; 11: 1061. doi: 10.3389/fimmu.2020.01061.

40. Wang N., Zhan Y., Zhu L. et al. Retrospective multicenter cohort study shows early interferon therapy is associated with favorable clinical responses in COVID-19 patients. Cell Host Microbe. 2020; 28 (3): 455–464. doi: 10.1016/j.chom.2020.07.005.

41. Логинова С.Я., Щукина В.Н., Савенко С.В., Борисевич С.В. Активность человеческого рекомбинантного интерферона альфа-2b in vitro в отношении вируса SARS-CoV-2. Вопросы Вирусологии. 2021; 66 (2): 123– 128. doi: https://doi.org/10.36233/0507-4088-13.

42. Li X., Liu T., Hai X., Li L. Interferon-α2b induced anemia in severe coronavirus disease 2019 patients: a single centered, retrospective study. Immunopharmacol Immunotoxicol. 2021; 43 (6): 644–650. doi: 10.1080/08923973.2021.1992634.

43. Popescu C., Arama V., Gliga S. Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis-case report. BMC Gastroenterol. 2011; 11 (1): 1–4. doi: 10.1186/1471-230X-11-30.

44. Вершинина С. Ф., Гершанович М. Л., Махнова Е. В., и др. Токсическое действие противоопухолевой терапии на сердечно-сосудистую систему. Вопросы онкологии. 2010; 56 (2): 234–239.

45. Sonnenblick M., Rosin A. Cardiotoxicity of interferon: a review of 44 cases. Chest. 1991; 99 (3): 557–561. doi: 10.1378/chest.99.3.557.

46. Rechciński T., Matusik D., Rudziński T. et al. Cardiotoxic properties of interferon. Pol Arch Med Wewn. 2007; 117 (1–2): 49–52.

47. Williams D.M. Clinical pharmacology of corticosteroids. Respir Care. 2018; 63 (6): 655–670. doi: 10.4187/respcare.06314.

48. Patel S.K., Saikumar G., Rana J. et al. Dexamethasone: A boon for critically ill COVID-19 patients?. Travel Med Infect Dis. 2020; 37: 101844. doi: 10.1016/j.tmaid.2020.101844.

49. Whitehouse M.W. Anti-inflammatory glucocorticoid drugs: reflections after 60 years. Inflammopharmacology. 2011; 19 (1): 1–9. doi: 10.1007/s10787-010-0056-2.

50. Iwabuchi K., Yoshie K., Kurakami Y. et al. Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: report of three cases. J Infect Chemother. 2020; 26 (6): 625–632. doi: 10.1016/j.jiac.2020.04.007.

51. El-Saber Batiha G., Al-Gareeb A.I., Saad H.M., Al-Kuraishy H.M. COVID-19 and corticosteroids: a narrative review. Inflammopharmacology. 2022; 30 (4): 1189–1205. doi: 10.1007/s10787-022-00987-z.

52. Broccoli M.C., Pigoga J.L., Nyirenda M. et al. Essential medicines for emergency care in Africa. Afr J Emerg Med. 2018; 8 (3): 110–117. doi: 10.1016/j.afjem.2018.05.002.

53. Russell C.D., Millar J.E., Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020; 395 (10223): 473–475. doi: 10.1016/S0140-6736(20)30317-2.

54. Souverein P.C., Berard A., Van Staa T.P. et al. Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case–control study. Heart. 2004; 90 (8): 859–865. doi: 10.1136/hrt.2003.020180.

55. Varas-Lorenzo C., Rodriguez L.A., Maguire A. et al. Use of oral corticosteroids and the risk of acute myocardial infarction. Atherosclerosis. 2007; 192 (2): 376–383. doi: 10.1016/j.atherosclerosis.2006.05.019.

56. Sanders B.P., Portman R.J., Ramey R.A. et al. Hypertension during reduction of long-term steroid therapy in young subjects with asthma. J Allergy Clin Immunol. 1992; 89 (4): 816–821. doi: 10.1016/00916749(92)90436-6.

57. Üsküdar Cansu D., Bodakçi E., Korkmaz C. Dose-dependent bradycardia as a rare side effect of corticosteroids: a case report and review of the literature. Rheumatol Int. 2018; 38 (12): 2337–2343. doi: 10.1007/s00296018-4167-1.

58. Kabinger F., Stiller C., Schmitzová J. et al. Mechanism of molnupiravirinduced SARS-CoV-2 mutagenesis. Nature Structural & Molecular Biology. 2021; 28 (9): 740–746. doi: 10.1038/s41594-021-00651-0.

59. Mahase E. COVID-19: Pfizer’s paxlovid is 89% effective in patients at risk of serious illness, company reports. BMJ. 2021; 375: n2713. doi: 10.1136/bmj.n2713.

60. Wen W., Chen C., Tang J. et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis. Ann Med. 2022; 54 (1): 516–523. doi: 10.1080/07853890.2022.2034936.