Journal of Literature Pharmacy Sciences

.: REVIEW
Geçmişten Günümüze Obezite Tedavisinde Kullanılan İlaçlar ve İstenmeyen Etkileri
Drugs Used in the Treatment of Obesity Since Decades and Their Adverse Effects
Cemre ŞAHİN ŞENYÜZa, Rengin REİSa,b, Hande SİPAHİa
aFarmasötik Toksikoloji AD, Yeditepe Üniversitesi Eczacılık Fakültesi, İstanbul, TÜRKİYE
bFarmasötik Toksikoloji AD, Karadeniz Teknik Üniversitesi Eczacılık Fakültesi, Trabzon, TÜRKİYE
J Lit Pharm Sci. 2019;8(1):61-75
doi: 10.5336/pharmsci.2018-62684
Article Language: TR
Full Text
ÖZET
 Obezite, vücuda alınan ve harcanan enerjideki dengesizlik sonucu ortaya çıkan 20. yüzyılın en önemli kronik rahatsızlıklarından biridir. Özellikle de değişen yaşam koşullarıyla birlikte fiziksel aktivite azalması ve kalorili beslenme alışkanlıklarının artması sebebiyle obezite insidansı her geçen gün artmaktadır. Obezite derecesindeki artışa paralel olarak mortalite ve kardiyovasküler hastalık riskinin de arttığı bildirilmektedir. Özellikle de diyabet patogenezinde, obezite ve kilo artışı önemli risk faktörleri arasında yer almaktadır. Bu nedenle obezite tedavisi, obezitenin yol açtığı kronik hastalıkların gelişimi açısından da önem taşımaktadır. Yaşam tarzı değişikliklerinin yanı sıra, geçmişten bu yana obezite tedavisinde, uzun veya kısa vadede kullanılan birçok antiobezite ilacı bulunmakta ve bir kısmı ile ilgili faz çalışmaları hâlâ devam etmektedir. Bu ilaçlardan bazıları ise istenmeyen advers etkileri nedeni ile piyasadan çekilmiştir. Bu çalışmada, geçmişten günümüze obezite tedavisinde kullanılan ilaçların toksikolojik açısından değerlendirilmesi ve advers etkilerinin incelenmesi amaçlanmıştır.

Anahtar Kelimeler: Obezite; advers etki; zayıflama ilaçları; sibutramin; orlistat
ABSTRACT
 Obesity is one of the most important chronic disorders of the 20th century, which is the result of the imbalance of the energy taken in the body and used. The incidence of obesity is increasing gradually, especially due to the changed physical conditions associated with lifestyle and high-calorie eating habits. In parallel, it is stated that the increase in the degree of obesity increases the risk of mortality and cardiovascular disease. Especially in the pathogenesis of diabetes, obesity and weight gain are important risk factors. Therefore, obesity treatment is also important for the development of chronic diseases caused by obesity. In addition to lifestyle changes, there have been many anti-obesity agents used in the long or short term in the treatment of obesity since the past, and some phase studies are still ongoing. Some of these drugs have been withdrawn from the market due to their unwanted adverse effects. The purpose of this review is to evaluate the toxicological aspects of the drugs used in the treatment of obesity and to investigate the adverse effects of these drugs.

Keywords: Obesity; adverse effect; weight loss medications; sibutramine; orlistat
REFERENCES:
  1. Halpern B, Oliveira ES, Faria AM, Halpern A, Melo ME, Cercato C, et al. Combinations of drugs in the treatment of obesity. Pharmaceuticals (Basel). 2010;3(8):2398-415. [Cross - ref] [PubMed] [PMC]
  2. Karakaya K, Baran E, Tüzün H, Göçmen L, Erata M, Arıkan İ, et al. [Research on perception of body weight in Turkey]. Akdağ R, editör. Turkiye Beden Ağırlığı Algısı Araştırması. Sağlık Bakanlığı Yayın No: 894. T.C. Turkiye Cumhuriyeti Sağlık Bakanlığı Sağlığın Geliştirilmesi Genel Müdürlüğü. Ankara: Anıl Matbaacılık Ltd Şti; 2012. p.16-8.
  3. World Health Organisation (WHO). Obesity and Overweight. WHO Official Website; 2018.
  4. Khan A, Raza S, Khan Y, Aksoy T, Khan M, Weinberger Y, et al. Current updates in the medical management of obesity. Recent Pat Endocr Metab Immune Drug Discov. 2012;6(2):117-28. [Crossref] [PubMed]
  5. World Health Organisation (WHO). Division of Noncommunicable Diseases Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation On Obesity. Geneva: WHO; 1997. p.79.
  6. Bray GA. A concise review on the therapeutics of obesity. Nutrition. 2000;16(10):953-60. [Crossref]
  7. Yen M, Ewald MB. Toxicity of weight loss agents. J Med Toxicol. 2012;8(2):145-52. [Crossref] [PubMed] [PMC]
  8. Tanakol R. [Orlistat in obesity treatment]. Turk J Endocrinol Metab. 2003;(Suppl 2):87-97.
  9. Jain SS, Ramanand SJ, Ramanand JB, Akat PB, Patwardhan MH, Joshi SR. Evaluation of efficacy and safety of orlistat in obese patients. Indian J Endocrinol Metab. 2011;15(2):99104. [Crossref] [PubMed] [PMC]
  10. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2003;27(1):155-61. [Crossref]
  11. Kujawska-Łuczak M, Musialik K, Szulińska M, Swora-Cwynar E, Kargulewicz A, Grzymisławska M, et al. The effect of orlistat versus metformin on body composition and insulin resistance in obese premenopausal women: 3-month randomized prospective open-label study. Arch Med Sci. 2017;13(4): 725-31. [Crossref] [PubMed] [PMC]
  12. Koca SS, Özkan Y, Akbulut H, Günay İ, Dönder E. [Decreased adinopectin level and effect of orlistat treatment in obesity]. Turkiye Klinikleri J Med Sci. 2006;26(2):126-31.
  13. Acharya NV, Wilton LV, Shakir SA. Safety profile of orlistat: results of a prescription-event monitoring study. Int J Obesity (Lond). 2006;30(11):1645-52. [Crossref] [PubMed]
  14. Xiao D, Shi D, Yang D, Barthel B, Koch TH, Yan B. Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs. Biochem Pharmacol. 2013;85(3):439-47. [Crossref] [PubMed] [PMC]
  15. Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2011;20(2):330-42. [Crossref] [PubMed] [PMC]
  16. Wadden TA, Berkowitz RI, Silvestry F, Vogt RA, St John Sutton MG, Stunkard AJ, et al. The fen-phen finale: a study of weight loss and valvular heart disease. Obes Res. 1998;6(4): 278-84. [Crossref] [PubMed]
  17. Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab. 2010;12(10):876-82. [Crossref] [PubMed]
  18. Kim HO, Lee JA, Suh HW, Kim YS, Kim BS, Ahn ES, et al. Postmarketing surveillance study of the efficacy and safety of phentermine in patients with obesity. Korean J Fam Med. 2013;34(6):298-306. [Crossref] [PubMed] [PMC]
  19. Stahl KA, Imperiale TF. An overview of the efficacy and safety of fenfluramine and mazindol in the treatment of obesity. Arch Fam Med. 1993;2(10):1033-8. [Crossref]
  20. Bray GA, Ryan DH. Update on obesity pharmacotherapy. Ann N Y Acad Sci. 2014;1311: 1-13. [Crossref] [PubMed]
  21. Catoira NP, Viale L, Di Girolamo G, Gonzalez C. New centrally acting agents for appetite control: from biological mechanisms to clinical efficacy. Curr Med Res Opin. 2014;30(6):961-9. [Crossref] [PubMed]
  22. Scientific conclusions and grounds for refusal presented by the European Medicines Agency: Overall summary of the scientific evaluation of Qsiva; 2013. p.10.
  23. FDA Center for Drug Evaluation and Research. Reference ID: 3160379. Summary Review for Regulatory Action Qsymia; 2013. p.18.
  24. Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for obesity: past, current, and future therapies. J Obes. 2011;2011: 179674. [Crossref] [PubMed] [PMC]
  25. Cheung BM, Cheung TT, Samaranayake NR. Safety of antiobesity drugs. Ther Adv Drug Saf. 2013;4(4):171-81. [Crossref] [PubMed] [PMC]
  26. Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med. 2004;164(9):994-1003. [Crossref] [PubMed]
  27. Türk Eczacılar Birliği (TEB). Sibutramin İçeren Ürünlerin Satışının Durdurulması ve Toplatılmasına Yönelik Geri Çekme Duyurusu. Sayı: 006064. Ankara: 2010.
  28. Ali O. Sibutramine: a safety profile. Br J Cardiol. 2003;10:137-40.
  29. Nisoli E, Carruba MO. An assessment of the safety and efficacy of sibutramine, an antiobesity drug with a novel mechanism of action. Obes Rev. 2000;1(2):127-39. [Crossref] [PubMed]
  30. Kang JG, Park CY. Anti-obesity drugs: a review about their effects and safety. Diabetes Metab J. 2012;36(1):13-25. [Crossref] [PubMed] [PMC]
  31. Kokaçya MH, Şahpolat M, Kurhan F. [First manic episode induced by over the counter slimming drug that contains sibutramine]. J Mood Disorders. 2014;4(3):126-9. [Crossref]
  32. Kayar H, Utku S. [Disease of our time: obesity and its treatment]. Mersin Üniv Sağlık Bilim Derg. 2013;6(2):1-8.
  33. Aronne LJ, Tonstad S, Moreno M, Gantz I, Erondu N, Suryawanshi S, et al. A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study. Int J Obes (Lond). 2010;34(5):919-35. [Crossref] [PubMed]
  34. Hurren KM, Berlie HD. Lorcaserin: an investigational serotonin 2C agonist for weight loss. Am J Health Syst Pharm. 2011;68(21):2029-37 [Crossref] [PubMed]
  35. European Medicine Agency (EMA). Withdrawal of the Marketing Authorisation Application for Belviq (Lorcaserin). EMA; 2013. Document Number: EMA/309180/2013.
  36. Kim GW, Lin JE, Blomain ES, Waldman SA. Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther. 2013;95(1):53-66. [Crossref] [PubMed] [PMC]
  37. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010; 363(3):245-56. [Crossref] [PubMed]
  38. Manning S, Pucci A, Finer N. Pharmacotherapy for obesity: novel agents and paradigms. Ther Adv Chronic Dis. 2014,5(3):135-48. [Crossref] [PubMed] [PMC]
  39. Dias S, Paredes S, Ribeiro L. Drugs involved in dyslipidemia and obesity treatment: focus on adipose tissue. Int J Endocrinol. 2018;2018:2637418. [Crossref] [PubMed] [PMC]
  40. Hendricks EJ. Off-label drugs for weight management. Diabetes Metab Syndr Obes. 2017;1:223-34.
  41. Scott LJ. Liraglutide: a review of its use in the management of obesity. Drugs. 2015;75(8): 899-910. [Crossref] [PubMed]
  42. Mancini MC, de Melo ME. The burden of obesity in the current world and the new treatments available: focus on liraglutide 3.0 mg. Diabetol Metabol Syndr. 2017;9:44. [Crossref] [PubMed] [PMC]
  43. Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, et al. Efects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009;374(9701):1606-16. [Crossref]
  44. Ladenheim EE. Liraglutide and obesity: a review of the data so far. Drug Des Devel Ther. 2015;1867-75. [Crossref] [PubMed] [PMC]
  45. Jeong KH, Yoo BK. The efficacy and safety of liraglutide. Int J Clin Pharm. 2011;33(5):740-9. [Crossref] [PubMed]
  46. Coulter AA, Rebello CJ, Greenway FL. Centrally acting agents for obesity: past, present, and future. Drugs. 2018;78(11):1113-32. [Crossref] [PubMed]
  47. Appolinario JC, Bueno JR, Coutinho W. Psychotropic drugs in the treatment of obesity: what promise? CNS Drugs. 2004;18(10):629[Crossref] [PubMed]
  48. McElroy SL, Guerdjikova AI, Martens B, Keck PE Jr, Pope HG, Hudson JI. Role of antiepileptic drugs in the management of eating disorders. CNS Drugs. 2009;23(2):139-56. [Crossref] [PubMed]
  49. McElroy SL, Keck PE Jr. Obesity in bipolar disorder: an overview. Curr Psychiatry Rep. 2012;14(6):650-8. [Crossref] [PubMed]
  50. Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003;289(14):1820-5. [Crossref] [PubMed]
  51. Srivastava G, Apovian C. Future pharmacotherapy for obesity: new anti-obesity drugs on the horizon. Curr Obes Rep. 2018;7(2): 147-61. [Crossref] [PubMed]
  52. Wharton S, Serodio KJ. Next generation of weight management medications: implications for diabetes and CVD risk. Curr Cardiol Rep. 2015;17(5):35. [Crossref] [PubMed] [PMC]
  53. Hollander P. Anti-diabetes and anti-obesity medications: effects on weight in people with diabetes. Diabetes Spectr. 2007;20(3):159-65. [Crossref]
  54. Malin SK, Kashyap SR. Effects of metformin on weight loss: potential mechanisms. Curr Opin Endocrinol Diabetes Obes. 2014;21(5): 323-9. [Crossref] [PubMed]
  55. Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014;170(3):451-9. [Crossref] [PubMed] [PMC]
  56. Erkekoğlu P, Baydar T, Şahin G. [Evaluation of obesity treatment approaches in geriatric group from atoxicological aspect-II: antiobesitic drugs]. Turkish Journal of Geriatrics. 2009;12(4):202-16.
  57. Igel LI, Sinha A, Saunders KH, Apovian CM, Vojta D, Aronne LJ. Metformin: an old therapy that deserves a new indication for the treatment of obesity. Curr Atheroscler Rep. 2016;18(4):16. [Crossref] [PubMed]
  58. de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ.2010;340:c2181. [Crossref] [PubMed] [PMC]
  59. Dunican KC, Adams NM, Desilets AR. The role of pramlintide for weight loss. Ann Pharmacother. 2010;44(3):538-45. [Crossref] [PubMed]
  60. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care. 2008;31(9):1816-23. [Cross - ref] [PubMed] [PMC]
  61. Ryan G, Briscoe TA, Jobe L. Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes. Drug Des Devel Ther. 2008;2:203-14. [Crossref]
  62. Riddle MC, Drucker DJ. Emerging therapies mimicking the effects of amylin and glucagonlike peptide 1. Diabetes Care. 2006;29(2):43549. [Crossref]
  63. Moretto TJ, Milton DR, Ridge TD, Macconell LA, Okerson T, Wolka AM, et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drugnaive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallelgroup study. Clin Ther. 2008;30(8):1448-60. [Crossref] [PubMed]
  64. Bunck MC, Diamant M, Eliasson B, Cornér A, Shaginian RM, Heine RJ, et al. Exenatide affects circulating cardiovascular risk biomark ers independently of changes in body composition. Diabetes Care. 2010;33(8):1734-7. [Crossref] [PubMed] [PMC]
  65. Krentz AJ, Fujioka K, Hompesch M. Anti-obesity pharmacotherapy: the intercontinental regulatory divide. Drugs. 2015;75(9):931-3. [Crossref] [PubMed]
  66. Ioannides-Demos LL, Proietto J, Tonkin AM, McNeil JJ. Safety of drug therapies used for weight loss and treatment of obesity. Drug Saf. 2006;29(4):277-302. [Crossref]
  67. Afkhami-Ardekani M, Sedghi H. Effect of fluoxetine on weight reduction in obese patients. Indian J Clin Biochem. 2005;20(1):135-8. [Crossref] [PMC]
  68. Maheux P, Ducros F, Bourque J, Garon J, Chiasson JL. Fluoxetine improves insulin sensitivity in obese patients with non-insulindependent diabetes mellitus independently of weight loss. Int J Obes Relat Metab Disord. 1997;21(2):97-102. [Crossref]
  69. Ricca V, Mannucci E, Mezzani B, Moretti S, Di Bernardo M, Bertelli M, et al. Fluoxetine and fluvoxamine combined with individual cognitive-behaviour therapy in binge eating disorder: a one-year follow-up study. Psychother Psychosom. 2001;70(6):298-306. [Crossref]
  70. Melendez G, Serralde-Zúñiga AE, Garay AGG, Rodríguez-Carmona Y, Galicia CS. Flu oxetine for adult overweight or obese people. Cochrane Database Syst Rev. 2015;5. [Cross ref]
  71. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995;3 Suppl 4:477S-480S. [Crossref]
  72. Halford JC, Harrold JA, Lawton CL, Blundell JE. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr Drug Targets. 2005;6(2):201-13. [Crossref]
  73. Cangiano C, Laviano A, Del Ben M, Preziosa I, Angelico F, Casinco A, et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord. 1988;22(7):648-54. [Crossref]
  74. Ceci F, Cangiano C, Cairella M, Cascino A, Del Ben M, Muscaritoli M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76(2):109-17. [Crossref]
  75. Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. BMC Med. 2016;14(1):191. [Crossref] [PMC]

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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