Journal of Literature Pharmacy Sciences

COVID-19: Güncel Tedavi Yaklaşımları ve Toksisitelerinin Değerlendirilmesi
COVID 19: Current Treatment Approaches and Evaluation of Their Toxicities
Ünzile SURa, Belma KOÇER GÜMÜŞELb
aHacettepe Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Ankara, TÜRKİYE
bLokman Hekim Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Ankara, TÜRKİYE
J Lit Pharm Sci. 2021;10(2):187-97
doi: 10.5336/pharmsci.2020-78662
Article Language: TR
Full Text
ÖZET
Dünya Sağlık Örgütü (DSÖ) tarafından 11 Mart 2020 tarihinde pandemi ilan edilmesini takiben yapılan araştırmalara karşın hâlen onaylanmış bir tedavisi bulunamamış olan koronavirüs hastalığı-2019 [coronavirus disease-2019 (COVID-19)], dünya çapında yayılmaya ve hastalığa bağlı ölüm vakaları artmaya devam etmektedir. Bu derleme çalışmasının yazıldığı tarih olan 26 Ağustos 2020 itibarıyla dünya çapında toplam 23.918.447 kişinin COVID-19 pozitif olduğu ve 819.945 kişinin öldüğü belirlenmiştir. Henüz hastalık etkeni şiddetli akut solunum sendromu-koronavirüs-2'ye karşı tedavide kullanılabilecek bilinen bir molekül bulunmadığından, başka viral hastalıkların tedavisinde kullanılan, etkinliği ve güvenliliği onaylanmış yöntemler ile ilgili birçok klinik araştırma devam etmektedir. Ayrıca birçok ülke eş zamanlı olarak olası aşı seçenekleri ile ilgili preklinik ve klinik araştırmaları sürdürmektedir. Ancak hastalığın yayılma hızı ve enfekte olduktan sonra özellikle riskli gruplarda çok kısa sürede morbiditenin gerçekleşmesi, yüksek dozlarda veya kombinasyonlar şeklinde tedavi uygulanmasını gerektirmekte, bu da advers etki görülme riskini artırmaktadır. Hastalığın keşfinden günümüze kadar gelen birçok tedavi seçeneği, hastalarda meydana gelen ciddi toksisite sebebiyle tedavi protokollerinden kaldırılmıştır. Bu derleme çalışmasının amacı, DSÖ'nün önerdiği ve sahada sıklıkla tercih edilen tedavi yöntemlerinin kullanım şekilleri ve olası toksisiteleri ile ilgili bir literatür özeti yapmaktır. Çalışmaya dâhil edilen etken madde ve diğer muhtemel tedavi yöntemleri, DSÖ'nün yürüttüğü 'Solidarity Trial' isimli kapsamlı ve uluslararası klinik araştırmaya dâhil edilen ayrıca doktorlar, eczacılar ve bilim insanları tarafından en çok tartışılanlar arasından seçilmiştir.

Anahtar Kelimeler: COVID-19; koronavirüs; SARS-COV-2; toksisite
ABSTRACT
Despite the research conducted by the World Health Organization (WHO) following the pandemic declaration on March 11, 2020, coronavirus disease-2019 (COVID-19), which has not yet found an approved treatment, continues to spread worldwide and increases the number of deaths due to the disease. As of August 26, 2020, a total of 23,918,447 people were COVID-19 positive and there were 819,945 deaths globally. Since there is no treatment of severe acute respiratory syndrome-coronavirus-2, many clinical studies are going on with previous methods which have approved efficacy and safety and used in the treatment of other viral diseases. In addition, many countries simultaneously conduct preclinical and clinical studies on possible vaccine options. However, the rate of spread of the disease and the occurrence of morbidity in a very short time after infection, especially in high risk groups, require high doses or combinations of treatment which increases the risk of adverse effects. Since the discovery of the disease, many treatment options have been removed from treatment protocols due to severe toxicity in patients. The purpose of this review is to make a literature summary on commonly used and recommended treatment options by WHO and their possible toxicities. The medicine options and other possible treatment methods included in the study were selected among the ones that were included in the comprehensive and international clinical study called "Solidarity Trial" conducted by WHO, and also among the most discussed by doctors, pharmacists and scientists.

Keywords: COVID-19; coronavirus; SARS-COV-2; toxicity
REFERENCES:
  1. Organization WH [İnternet]. © 2020 WHO [Erişim tarihi: 08.05.2020]. Rolling updates on coronavirus disease (COVID-19). Erişim linki: [Link] 
  2. Medicine JHUo [İnternet]. © 2020 by Johns Hopkins University & Medicine [Erişim tarihi: 26.08.2020]. Johns Hopkins University of Medicine Coronavirus Research Center. Erişim linki: [Link] 
  3. T.C. Sağlık Bakanlığı [İnternet]. Copyright © 2020 T.C. Sağlık Bakanlığı [Erişim tarihi: 26.08.2020]. T.C. Sağlık Bakanlığı Korona Tablosu. Erişim linki: [Link] 
  4. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-74. [Crossref]  [PubMed]  [PMC] 
  5. Gorbalenya AE, Baker SC, Baric R, Groot RJ, Drosten C, Gulyaeva AA, et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses-a statement of the Coronavirus Study Group. BioRxiv. 2020. [Crossref] 
  6. Fung TS, Liu DX. Human Coronavirus: Host-Pathogen Interaction. Annu Rev Microbiol. 2019;73:529-57. [Crossref]  [PubMed] 
  7. Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et al. Bats are natural reservoirs of SARS-like coronaviruses. Science. 2005;310(5748):676-9. [Crossref]  [PubMed] 
  8. Corman VM, Ithete NL, Richards LR, Schoeman MC, Preiser W, Drosten C, et al. Rooting the phylogenetic tree of middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat. J Virol. 2014;88(19):11297-303. [Crossref]  [PubMed]  [PMC] 
  9. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3. [PubMed]  [PMC] 
  10. Ji W, Wang W, Zhao X, Zai J, Li X. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol. 2020;92(4):433-440. [Crossref]  [PubMed]  [PMC] 
  11. Liu P, Chen W, Chen JP. Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica). Viruses. 2019;11(11):979. [Crossref]  [PubMed]  [PMC] 
  12. Yang X, Yu Y, Xu J, Shu H, Liu H, Wu Y, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020;8(5):475-481. [Crossref] 
  13. Pan H, Peto R, Karim QA, Alejandria M, Henao-Restrepo AM, García CH, et al. Repurposed antiviral drugs for COVID-19 -interim WHO SOLIDARITY trial results. medRxiv. 2020. [Link] 
  14. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69. [Crossref]  [PubMed]  [PMC] 
  15. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71. [Crossref]  [PubMed]  [PMC] 
  16. T.C. Sağlık Bakanlığı [İnternet]. [Erişim tarihi: 20.11.2020] COVID-19 (SARS-CoV-2 Enfeksiyonu) Erişkin Hasta Tedavisi. Erişim linki: [Link] 
  17. T.C. Sağlık Bakanlığı [İnternet]. [Erişim tarihi: 20.11.2020]. COVID-19 (SARS-CoV2 Enfeksiyonu) Tedavisinde Kullanılacak İlaçlara İlişkin Bilgilendirme Hidroksiklorokin Sülfat 200 Mg Film Tablet. Erişim linki: [Link] 
  18. Riou B, Barriot P, Rimailho A, Baud FJ. Treatment of severe chloroquine poisoning. N Engl J Med. 1988;318(1):1-6. [Crossref]  [PubMed] 
  19. Guly U, Driscoll P. The management of quinine-induced blindness. Arch Emerg Med. 1992;9(3):317-22. [Crossref]  [PubMed]  [PMC] 
  20. Smith ER, Klein-Schwartz W. Are 1-2 dangerous? Chloroquine and hydroxychloroquine exposure in toddlers. J Emerg Med. 2005;28(4):437-43. [Crossref]  [PubMed] 
  21. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949. [Crossref]  [PubMed]  [PMC] 
  22. Mahevas M, Tran VT, Roumier M, Chabrol A, Paule R, Guillaud C, et al. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial. Medrxiv. 2020. [Link] 
  23. Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849. [Crossref]  [PubMed]  [PMC] 
  24. Huang M, Tang T, Pang P, Li M, Ma R, Lu J, et al. Treating COVID-19 with Chloroquine. J Mol Cell Biol. 2020;12(4):322-5. [Crossref]  [PubMed]  [PMC] 
  25. Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020;383(6):517-525. [Crossref]  [PubMed]  [PMC] 
  26. World Health Organization [İnternet]. © 2020 WHO [Erişim tarihi: 08.07.2020] "Solidarity" clinical trial for COVID-19 treatments. Erişim linki: [Link] 
  27. Goldman JD, Lye DC, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. New England Journal of Medicine. 2020; 383:1827-1837. [Crossref] 
  28. National Institute of Health [İnternet]. [Erişim tarihi: 13.08.2020]. COVID-19 Treatment Guideline: Remdesivir. Erişim linki: [Link] 
  29. Gilead [İnternet]. [Erişim tarihi: 13.08.2020]. Summary on compassionate use remdesivir. Erişim linki: [Link] 
  30. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020;382(24):2327-36. [PubMed]  [PMC] 
  31. Gilead [İnternet]. © 2020 Gilead Sciences [Erişim tarihi: 13.08.2020]. Gilead announces results from phase 3 trial of investigational antiviral remdesivir in patients with severe COVID-19. Erişim linki: [Link] 
  32. Jin Z, Smith LK, Rajwanshi VK, Kim B, Deval J. The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5'-triphosphate towards influenza A virus polymerase. PLoS One. 2013;8(7):e68347. [Crossref]  [PubMed]  [PMC] 
  33. Choy KT, Wong AY, Kaewpreedee P, Sia SF, Chen D, Hui KPY, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020;178:104786. [Crossref]  [PubMed]  [PMC] 
  34. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering. 2020;10(6):1192-8. [Crossref] 
  35. T.C. Sağlık Bakanlığı [İnternet]. [Erişim tarihi: 19.11.2020]. COVID-19 (SARS-CoV2 Enfeksiyonu) Tedavisinde Kullanılacak İlaçlara İlişkin Bilgilendirme Favipiravir 200 Mg Tablet. Erişim linki: [Link] 
  36. World Health Organization [İnternet]. © 2020 WHO [Erişim tarihi: 13.08.2020]. COVID-19 Informal consultation on the potential inclusion of Favipiravir in a clinical trial. Erişim linki: [Link]  (Accessed August 13 2020).
  37. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327-47. [Crossref]  [PubMed]  [PMC] 
  38. Tahir Ul Qamar M, Alqahtani SM, Alamri MA, Chen LL. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal. 2020;10(4):313-9. [Crossref]  [PubMed]  [PMC] 
  39. Liu X, Wang XJ. Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines. J Genet Genomics. 2020;47(2):119-21. [Crossref]  [PubMed]  [PMC] 
  40. Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31(1): 69-75. [Crossref]  [PubMed]  [PMC] 
  41. Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al; HKU/UCH SARS Study Group. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3):252-6. [Crossref]  [PubMed]  [PMC] 
  42. Hull MW, Montaner JS. Ritonavir-boosted protease inhibitors in HIV therapy. Ann Med. 2011;43(5):375-88. [Crossref]  [PubMed] 
  43. Park SY, Lee JS, Son JS, Ko JH, Peck KR, Jung Y, et al. Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. J Hosp Infect. 2019;101(1):42-6. [Crossref]  [PubMed]  [PMC] 
  44. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-99. [PubMed]  [PMC] 
  45. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, et al; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020;323(15):1488-94. Erratum in: JAMA. 2020;323(15):1510. [Crossref]  [PubMed]  [PMC] 
  46. Liu F, Xu A, Zhang Y, Xuan W, Yan T, Pan K, et al. Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis. 2020;95:183-191. [Crossref]  [PubMed]  [PMC] 
  47. Roberts DM, Ray JE, Buckley NA. Mild clinical toxicity and dose-dependent pharmacokinetics following acute lopinavir/ritonavir poisoning in a HIV-positive patient. AIDS. 2008;22(6):792-3. [Crossref]  [PubMed] 
  48. López Aspiroz E, Cabrera Figueroa SE, Iglesias Gómez A, Valverde Merino MP, Domínguez-Gil Hurlé A. CYP3A4 polymorphism and lopinavir toxicity in an HIV-infected pregnant woman. Clin Drug Investig. 2015;35(1):61-6. [Crossref]  [PubMed] 
  49. Aspiroz EL, Cabrera Figueroa SE, Cruz R, Porras Hurtado GL, Martín AF, Hurlé AD, et al. Toxicogenetics of lopinavir/ritonavir in HIV-infected European patients. Per Med. 2014;11(3):263-272. [Crossref]  [PubMed] 
  50. Florence E, Schrooten W, Verdonck K, Dreezen C, Colebunders R. Rheumatological complications associated with the use of indinavir and other protease inhibitors. Ann Rheum Dis. 2002;61(1):82-4. [Crossref]  [PubMed]  [PMC] 
  51. Cresswell FV, Tomlins J, Churchill DR, Walker-Bone K, Richardson D. Achilles tendinopathy following Kaletra (lopinavir/ritonavir) use. Int J STD AIDS. 2014;25(11):833-5. [Crossref]  [PubMed] 
  52. COVID Treatmen Guidelines [İnternet]. [Erişim tarihi: 14.08.2020]. Lopinavir/Ritonavir and Other HIV Protease Inhibitors. Erişim linki: [Link] 
  53. Pearce L, Davidson SM, Yellon DM. The cytokine storm of COVID-19: a spotlight on prevention and protection. Expert Opin Ther Targets. 2020;24(8):723-30. [Crossref]  [PubMed] 
  54. Xiang Z, Liu J, Shi D, Chen W, Li J, Yan R, et al. Glucocorticoids improve severe or critical COVID-19 by activating ACE2 and reducing IL-6 levels. Int J Biol Sci. 2020;16(13):2382-91. [Crossref]  [PubMed]  [PMC] 
  55. Ledford H. Coronavirus breakthrough: dexamethasone is first drug shown to save lives. Nature. 2020;582(7813):469. [Crossref]  [PubMed] 
  56. National Institute of Health [İnternet]. [Erişim tarihi: 15.08.2020]. COVID-19 Treatment Guidelines Corticosteroids. Erişim linki: [Link] 
  57. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, et al; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015;211(1):80-90. [Crossref]  [PubMed]  [PMC] 
  58. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020;323(16):1582-9. [Crossref]  [PubMed]  [PMC] 
  59. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020;117(17):9490-6. [Crossref]  [PubMed]  [PMC] 
  60. Zeng QL, Yu ZJ, Gou JJ, Li GM, Ma SH, Zhang GF, et al Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019. J Infect Dis. 2020;222(1):38-43. [Crossref]  [PubMed]  [PMC] 
  61. U.S. National Library of Medicine [İnternet]. [Erişim tarihi: 15.08.2020]. Search of onvalescent and covid19. Erişim linki: [Link] 
  62. World Health Organization [İnternet]. © 2020 WHO [Erişim tarihi: 15.08.2020]. Webinar on Collection of COVID-19 Convalescent Plasma. Erişim linki: [Link] 
  63. T.C. Sağlık Bakanlığı [İnternet]. [Erişim tarihi: 18.11.2020]. COVID-19 İmmün (Konvalesan) Plazma Tedarik ve Klinik Kullanım Rehberi. Erişim linki: [Link] 
  64. Barone P, DeSimone RA. Convalescent plasma to treat coronavirus disease 2019 (COVID-19): considerations for clinical trial design. Transfusion. 2020;60(6):1123-7. [Crossref]  [PubMed]  [PMC] 
  65. World Health Organization [İnternet]. © 2020 WHO [Erişim tarihi: 15.08.2020]. Draft landscape of COVID-19 candidate vaccines. Erişim linki: [Link] 
  66. Modjarrad K, Roberts CC, Mills KT, Castellano AR, Paolino K, Muthumani K, et al. Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis. 2019;19(9):1013-22. [Crossref]  [PubMed]  [PMC] 
  67. Pardi N, Hogan MJ, Weissman D. Recent advances in mRNA vaccine technology. Curr Opin Immunol. 2020;65:14-20. [Crossref]  [PubMed] 
  68. Pfizer [İnternet]. Copyright © 2002-2021 Pfizer Inc [Erişim tarihi: 20.11.2020]. Pfizer and Biontech to Submit Emergency Use Authorization Request Today to The U.S. FDA For COVID-19 Vaccine. Erişim linki: [Link] 
  69. ModernaTX [İnternet]. © 2020 Moderna [Erişim tarihi: 16.08.2020]. Moderna's Work on a COVID-19 Vaccine Candidate. Erişim linki: [Link] 
  70. AstraZeneca [İnternet]. © AstraZeneca 2020 [Erişim tarihi: 16.11.2020]. FDA authorises restart of the COVID-19 AZD1222 vaccine US Phase III trial. Erişim linki: [Link] 
  71. Al Jazeera [İnternet]. © 2021 Al Jazeera Media Network [Erişim tarihi: 16.08.2020]. Sputnik V: What we know about Russia's coronavirus vaccine. Erişim linki: [Link] 
  72. Uppsala Monitoring Centre [İnternet]. [Erişim tarihi: 19.11.2020]. How to capture ICSRs for COVID-19 treatments. Erişim linki: [Link] 

.: Up To Date

.: Process List

Login



Contact


Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com