{"id":3177,"date":"2019-09-07T20:16:27","date_gmt":"2019-09-07T17:16:27","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=3177"},"modified":"2019-09-07T20:16:29","modified_gmt":"2019-09-07T17:16:29","slug":"tip-tarihinin-kara-lekesi-talidomid-faciasi","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/tip-tarihinin-kara-lekesi-talidomid-faciasi\/","title":{"rendered":"T\u0131p Tarihinin Kara Lekesi: Talidomid Facias\u0131"},"content":{"rendered":"\n
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Kaynak:<\/em><\/strong> Leonard McCombe\/Time Life Pictures\/Getty Images <\/figcaption><\/figure>\n\n\n\n

\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nTalidomid,\n1950\u2019li y\u0131llar\u0131n sonunda Chemie-Grunenthal\nGmbH<\/em> adl\u0131 Bat\u0131 Almanya\u2019da bulunan bir ila\u00e7 \u015firketi taraf\u0131ndan piyasaya\nsunuldu. \u0130lk ba\u015flarda etkili bir sedatif (yat\u0131\u015ft\u0131r\u0131c\u0131) olarak bilinen ila\u00e7 daha\nsonralar\u0131 antiemetik (kusma \u00f6nleyici) etkinli\u011finin de ortaya konulmas\u0131yla\nhamile kad\u0131nlarda g\u00f6r\u00fclen sabah bulant\u0131lar\u0131n\u0131n da tedavisinde kullan\u0131lmaya\nba\u015fland\u0131. \u0130la\u00e7 birka\u00e7 y\u0131l i\u00e7inde \u00f6zellikle hamile kad\u0131nlar aras\u0131nda \u00f6ylesine\npop\u00fclerle\u015fti ki kullan\u0131lmas\u0131n\u0131n yasakland\u0131\u011f\u0131 1961 y\u0131l\u0131na kadar \u0130ngiltere ve\nAvustralya’da Distaval<\/em>, Almanya\u2019da Contergan<\/em>, Avrupa\u2019n\u0131n geri kalan\u0131nda Softernon <\/em>ad\u0131yla olmak \u00fczere d\u00fcnya\ngenelinde tam 46 \u00fclkede kullan\u0131l\u0131r hale geldi. Fakat \u00e7ok \u00f6nemli bir ger\u00e7ek g\u00f6z\nard\u0131 ediliyordu; bilim insanlar\u0131 ila\u00e7 \u00fczerinde yap\u0131lan testlerde pratik olarak \u00f6l\u00fcmc\u00fcl a\u015f\u0131r\u0131 doz (LD50)<\/em> seviyelerinin\nbelirlenmesinin imk\u00e2ns\u0131z oldu\u011funu fark etmi\u015flerdi ve hayvanlar \u00fczerinde yap\u0131lan\ntestlerin hi\u00e7birinde denekler ilac\u0131n hamilelik s\u00fcrecindeki yan etkilerine kar\u015f\u0131\nizlenmemi\u015fti.\n\n\n\n<\/p>\n\n\n\n

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Kaynak:<\/em><\/strong> Thalidomide\u2010induced teratogenesis: History and mechanisms <\/figcaption><\/figure>\n\n\n\n

Ba\u015flarda her \u015fey iyi gidiyordu. \u0130la\u00e7, sabah bulant\u0131s\u0131ndan \u015fikayet\u00e7i hamile kad\u0131nlar aras\u0131nda h\u0131zla yay\u0131l\u0131yor bunun yan\u0131 s\u0131ra anksiyete hastalar\u0131nda g\u00f6r\u00fclen hafif semptomlar\u0131 \u00f6nlemek i\u00e7in de tavsiye ediliyordu. \u00d6yleki ilac\u0131n pazarlamas\u0131n\u0131 yapan baz\u0131 firmalar talidomidi \u201ctamamen zarars\u0131z\u201d<\/em><\/strong>, \u201ctoksik olmayan\u201d<\/em><\/strong>, \u201czehir i\u00e7ermeyen\u201d<\/em><\/strong>, \u201cg\u00fcvenli\u201d<\/em><\/strong> gibi tan\u0131mlarla piyasaya s\u00fcr\u00fcyordu. B\u00fct\u00fcn bu pazarlama y\u00f6ntemlerinin \u0131\u015f\u0131\u011f\u0131nda talidomid d\u00f6nemin en \u00e7ok sat\u0131lan ila\u00e7lar\u0131ndan biri haline gelmi\u015fti. Fakat 1960\u2019l\u0131 y\u0131llara gelindi\u011finde doktorlar ilac\u0131n muhtemel yan etkileri olabilece\u011finden \u015f\u00fcphelenmeye ba\u015flam\u0131\u015flard\u0131. Bunlardan baz\u0131lar\u0131 periferal n\u00f6ropati, uzun s\u00fcreli kullan\u0131ma ba\u011fl\u0131 bacaklarda geli\u015fen sinir hasarlar\u0131 ve en \u00f6nemlisi a\u011f\u0131r konjenital defektlerle d\u00fcnyaya gelen fokomelili \u00e7ocuklard\u0131. Alman Chemie-Grunenthal firmas\u0131 vakalar\u0131n talidomid ile ili\u015fkili oldu\u011funu inand\u0131r\u0131c\u0131 bir klinik kan\u0131t sunmaks\u0131z\u0131n defalarca reddetti. Anla\u015f\u0131lan, ila\u00e7 hi\u00e7 de s\u00f6ylendi\u011fi gibi \u201ctamamen zarars\u0131z\u201d<\/em><\/strong> de\u011fildi. <\/p>\n\n\n\n

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Talidomid facias\u0131ndan sonra 7 A\u011fustos 1962’de The New Zealand Truth gazetesinden bir k\u00fcp\u00fcr.<\/em>
Kaynak:<\/em><\/strong>https:\/\/corpus.nz\/wp-content\/uploads\/2016\/07\/Thalidomide_article_1962-08-07-2.jpg<\/figcaption><\/figure>\n\n\n\n

Agnes Donnelion, hamileli\u011fi boyunca dayan\u0131lmaz sabah bulant\u0131lar\u0131ndan \u015fikayet\u00e7iydi ve \u00e7areyi Contergan (talidomid)<\/em> kullanmakta bulmu\u015ftu. Hamilelik s\u00fcrecinin sonunda do\u011fum ger\u00e7ekle\u015fti fakat Donnelion o\u011flu Kevin\u2019i do\u011fumdan sonraki iki g\u00fcn boyunca kuca\u011f\u0131na alamad\u0131 hatta onu g\u00f6rmesine bile izin verilmedi. Donnelion hari\u00e7 servisteki di\u011fer b\u00fct\u00fcn anneler bebeklerini kucaklar\u0131na alabiliyordu, Donnelion hem\u015fireye \u201cBen neden bebe\u011fimi g\u00f6remiyorum?\u201d<\/em> diye sordu\u011funda hem\u015fire \u201cBebe\u011fini yar\u0131n g\u00f6rebilirsin\u2026 \u015eu anda durumu \u00e7ok iyi de\u011fil.\u201d<\/em> Cevab\u0131n\u0131 verdi. Donnelion, aradan ge\u00e7en iki g\u00fcn\u00fcn ard\u0131ndan Kevin\u2019\u0131 g\u00f6rebilmek i\u00e7in tekerlekli sandalyeyle bebe\u011finin yan\u0131na g\u00f6t\u00fcr\u00fcld\u00fc. Onu be\u015fi\u011fin yan\u0131na getiren hem\u015fire Donnelion\u2019a d\u00f6nerek \u201cBu arada\u2026 bebe\u011fin kollar\u0131 ve ayaklar\u0131 k\u0131sa,\u201d<\/em> dedi. O an bunun tam olarak ne anlama geldi\u011fini kavrayamayan Donnelion bebe\u011fini kuca\u011f\u0131na al\u0131p battaniyesini a\u00e7t\u0131\u011f\u0131nda hayat\u0131n\u0131n \u015fokunu ya\u015fad\u0131. \u00c7\u00fcnk\u00fc Kevin\u2019\u0131n kollar\u0131 ve bacaklar\u0131 normal bir k\u0131sal\u0131kta de\u011fildi, neredeyse hi\u00e7 yok gibilerdi. Maalesef Kevin Donnelion ne ilk ne de son kurban olacakt\u0131. Talidomid, kullan\u0131m\u0131n\u0131n yasakland\u0131\u011f\u0131 1961 y\u0131l\u0131na kadar d\u00fcnya genelinde 10.000\u2019i a\u015fk\u0131n \u00e7ocu\u011fun a\u011f\u0131r konjenital defektli olarak d\u00fcnyaya gelmesine sebep oldu. <\/p>\n\n\n\n

T\u00fcm bu ya\u015fananlara ra\u011fmen ila\u00e7 firmalar\u0131 hala olanlar\u0131 talidomid ile ili\u015fkilendirmekten ka\u00e7\u0131n\u0131yorlard\u0131. Fakat ka\u00e7\u0131n\u0131lmaz son yak\u0131nd\u0131. \u0130lk olarak 1961 y\u0131l\u0131nda Alman bir \u00e7ocuk doktoru olan Widukind Lenz, ard\u0131ndan 1962 y\u0131l\u0131nda Avustralyal\u0131 bir kad\u0131n do\u011fum uzman\u0131 olan William McBride talidomidin teratojenik etkinli\u011fini ortaya koydu. \u0130lk ba\u015flarda sadece ekstremite olu\u015fumunun engellenmesinden sorumlu oldu\u011fu d\u00fc\u015f\u00fcn\u00fclen talidomid sonralar\u0131 konjenital kalp hastal\u0131klar\u0131, i\u00e7 ve d\u0131\u015f kulaktaki malformasyonlar, ok\u00fcler anomaliler ile de ili\u015fkilendirildi. Talidomidin embriyo \u015fekillenmesi s\u0131ras\u0131nda meydana getirdi\u011fi hasar \u201ckritik d\u00f6nem\u201d<\/em><\/strong> olarak da bilinen k\u0131sa ve hassas bir zaman aral\u0131\u011f\u0131nda etkiliydi. Bu d\u00f6nem genellikle fertilizasyon sonras\u0131ndaki ilk 20 ve 36\u2019nc\u0131 g\u00fcnler aras\u0131n\u0131 kaps\u0131yor. Her ne kadar ilac\u0131n bu d\u00f6nemden \u00f6nce kullan\u0131l\u0131p b\u0131rak\u0131lmas\u0131 veya sonra kullan\u0131lmas\u0131 herhangi bir etkiye yol a\u00e7m\u0131yor gibi g\u00f6z\u00fckse de erken d\u00f6nemde kullan\u0131m\u0131n insanlarda ve farelerde d\u00fc\u015f\u00fc\u011fe, ge\u00e7 d\u00f6nemde kullan\u0131m\u0131n ise farelerde beyin hasar\u0131na sebep oldu\u011fu g\u00f6r\u00fcld\u00fc. Bu da talidomid kullan\u0131m\u0131n\u0131n hamileli\u011finin hi\u00e7bir d\u00f6neminde g\u00fcvenli olmad\u0131\u011f\u0131n\u0131 g\u00f6steriyordu. B\u00fct\u00fcn bu ger\u00e7ekler ortaya \u00e7\u0131k\u0131p da talidomid yasakland\u0131\u011f\u0131nda bile normalde de re\u00e7etesiz sat\u0131lan ila\u00e7 bir s\u00fcre daha el alt\u0131ndan sat\u0131lmay\u0131 s\u00fcrd\u00fcrd\u00fc. <\/p>\n\n\n\n

\"\"
Talidomidin “kritik d\u00f6nem” de yaratabilece\u011fi hasarla<\/em>r
Kaynak<\/strong>:<\/em> Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease <\/figcaption><\/figure>\n\n\n\n

Talidomid Kahraman\u0131 Dr. Frances Oldham Kelsey<\/strong><\/h2>\n\n\n\n

Avrupa\u2019n\u0131n hen\u00fcz Talidomid facias\u0131n\u0131n tam olarak fark\u0131na\nvaramad\u0131\u011f\u0131 y\u0131llarda Amerikan ila\u00e7 firmas\u0131 Merrel, Eyl\u00fcl 1960\u2019da talidomidi Kevadon<\/em> ismi ile piyasaya s\u00fcrmek \u00fczere\nAmerikan \u0130la\u00e7 ve G\u0131da Dairesi\u2019ne (FDA) ba\u015fvurmu\u015ftu. Ba\u015fvuru dosyas\u0131, rutin bir\nba\u015fvuru olarak g\u00f6r\u00fcld\u00fc\u011f\u00fc ve halihaz\u0131rda Avrupa\u2019da kullan\u0131ld\u0131\u011f\u0131 i\u00e7in h\u0131zl\u0131ca\nonaylanma beklentisi ile yak\u0131n zamanda FDA\u2019 da yeni ila\u00e7lara lisans veren\nbirimde raport\u00f6r olarak \u00e7al\u0131\u015fmaya ba\u015flayan aile hekimli\u011fi de yapm\u0131\u015f Dr. Frances\nOldham Kelsey\u2019in \u00f6n\u00fcne gelmi\u015fti. <\/p>\n\n\n\n

\u0130lac\u0131n g\u00fcvenli\u011fi ile ilgili baz\u0131 veriler Dr. Kelsey\u2019in dikkatini \u00e7ekmi\u015f ve Merrel firmas\u0131ndan \u00f6zellikle ila\u00e7la ilgili toksisite, dayan\u0131kl\u0131l\u0131k ve safl\u0131k konular\u0131nda ek bilgiler istemi\u015fti. G\u00f6nderilmesi istenen ek verilerle birlikte Dr. Kelsey ile Merrel firmas\u0131 aras\u0131nda ipler gerilmeye ba\u015flam\u0131\u015ft\u0131. Merrel firmas\u0131 istenilen verileri sunduk\u00e7a Dr. Kelsey daha \u00e7ok veri talebinde bulunmu\u015f ve sonunda Merrel firmas\u0131n\u0131n yetkilileri Dr. Kelsey\u2019i \u00fcst mercilere \u015fik\u00e2yet ederek kendilerine \u201ck\u00fc\u00e7\u00fck noktalar\u201d<\/em> \u00fczerinden b\u00fcrokratik engeller \u00e7\u0131kard\u0131klar\u0131n\u0131 s\u00f6ylemi\u015fti. Sonraki y\u0131llarda Dr. Kelsey bu d\u00f6nemi anlat\u0131rken Merrel firmas\u0131n\u0131n ruhsat almak i\u00e7in \u00e7ok hevesli ve aceleci davrand\u0131\u011f\u0131n\u0131, kendisi \u00fczerinde bask\u0131 kurduklar\u0131n\u0131 ve de\u011ferlendirme s\u00fcrecini etkilemeye \u00e7al\u0131\u015ft\u0131klar\u0131n\u0131, kendisinin en ba\u015f\u0131ndan itibaren firma yetkililerinin verdi\u011fi bilgiler konusunda \u015f\u00fcphe duydu\u011funu, onlara g\u00fcvenmedi\u011fini s\u00f6yleyecekti. <\/p>\n\n\n\n

Dr. Kelsey\u2019in Merrel firmas\u0131na kar\u015f\u0131 g\u00f6sterdi\u011fi direni\u015f devam ederken \u015eubat 1961\u2019de \u0130ngiliz T\u0131p Dergisi\u2019nde (BMJ), bir hekimin talidomidin bebeklerde kol ve bacak geli\u015fimini bozdu\u011funu belirten bir mektubun yay\u0131nlanmas\u0131 \u00fczerine bunu okuyan Dr. Kelsey, Merrel firmas\u0131na bu konuyu sordu. Firma i\u00e7 soru\u015fturma ba\u015flatt\u0131klar\u0131n\u0131 s\u00f6yledi ama Dr. Kelsey\u2019in iddialar\u0131n\u0131 yinelemesi \u00fczerine bu sefer firma yetkililerinden \u201cVeriler bir sonuca varmak, karar vermek i\u00e7in yeterli de\u011fil\u201d<\/em> cevab\u0131 geldi. Bu cevaptan tam 6 ay sonra Avrupa\u2019dan \u201cfokomeli epidemisi\u201d ile talidomid aras\u0131ndaki ili\u015fkiye ait raporlar gelmeye ba\u015flad\u0131 ve bir s\u00fcre sonra Merrel firmas\u0131 Kevadon<\/em> ile ilgili ba\u015fvurusunu geri \u00e7ekti. B\u00f6ylece Avrupa\u2019da binlerce bebek talidomid facias\u0131ndan etkilenirken, ABD\u2019de yaln\u0131zca 17 bebek etkilendi. <\/p>\n\n\n\n

G\u00fcn\u00fcm\u00fczde Talidomid<\/strong><\/h2>\n\n\n\n

\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nD\u00fcnya\ngenelinde h\u0131zla yasaklanmas\u0131n\u0131n ard\u0131ndan talidomid \u00fczerinde yap\u0131lan\n\u00e7al\u0131\u015fmalar\u0131n say\u0131s\u0131 olduk\u00e7a artm\u0131\u015ft\u0131. Bilim insanlar\u0131 talidomidin etki\nmekanizmas\u0131n\u0131 ve \u00f6zelliklerini tam olarak anlamaya \u00e7al\u0131\u015f\u0131yordu. 1964 y\u0131l\u0131nda\n\u0130srail\u2019de elindeki t\u00fcm yat\u0131\u015ft\u0131r\u0131c\u0131 ve a\u011fr\u0131 kesicileri denemesine ra\u011fmen\nc\u00fczzaml\u0131 hastas\u0131n\u0131n ac\u0131s\u0131n\u0131 dindiremeyen Dr. Jacob Sheskin hastas\u0131na talidomid\nverdi ve talidomidin c\u00fczzam\u0131n semptomlar\u0131n\u0131 azaltt\u0131\u011f\u0131n\u0131 g\u00f6zlemledi. 1967\ny\u0131l\u0131nda D\u00fcnya Sa\u011fl\u0131k \u00d6rg\u00fct\u00fc (WHO) talidomidin c\u00fczzam \u00fczerindeki etkileri ile\nilgili ara\u015ft\u0131rmas\u0131n\u0131 tamamlad\u0131. 1998 y\u0131l\u0131nda Amerikan \u0130la\u00e7 ve G\u0131da Dairesi\n(FDA) de talidomide c\u00fczzam\u0131n tedavisinde kullan\u0131lmas\u0131 amac\u0131yla k\u0131s\u0131tl\u0131 kullan\u0131m\nizni verdi. G\u00fcn\u00fcm\u00fczde talidomid, D\u00fcnya Sa\u011fl\u0131k \u00d6rg\u00fct\u00fc taraf\u0131ndan \u00f6nerilmemekle\nbirlikte c\u00fczzaml\u0131 hastalar\u0131n tedavisinde etkili bir ila\u00e7. Bunun yan\u0131nda anti inflamatuar\nve anti anjiyojenik \u00f6zellikleri sebebiyle A\u0130DS ve multiple miyolom gibi ciddi\nhastal\u0131klar\u0131n tedavisinde de kullan\u0131l\u0131yor.\n\n\n\n<\/p>\n\n\n\n

Facian\u0131n Ard\u0131ndan\u2026<\/strong><\/h2>\n\n\n\n

1957\u2019den 1961 y\u0131l\u0131na kadar hamile kad\u0131nlar\u0131n sabah\nbulant\u0131s\u0131n\u0131 \u00f6nlemek i\u00e7in kulland\u0131klar\u0131 talidomid on bini a\u015fk\u0131n fokomelili\n\u00e7ocu\u011fun do\u011fumundan sorumlu tutuldu. B\u00f6lgede g\u00f6r\u00fclen fokomeli epidemisi yasa\u011f\u0131n\nard\u0131ndan h\u0131zla normale d\u00f6nd\u00fc. Dr. Frances Kelsey gibi bilim insanlar\u0131 sayesinde\nfarmakoloji, toksikoloji gibi bilimlerin gereklili\u011fi anla\u015f\u0131ld\u0131, ila\u00e7lar \u00fczerinde\nuygulanan testler, d\u00fczenlemeler ve prosed\u00fcrler kat\u0131la\u015ft\u0131r\u0131ld\u0131. <\/p>\n\n\n\n

B\u00f6yle bir facian\u0131n hi\u00e7bir zaman tekrarlanmamas\u0131 diliyor ve \u00fclkemizin bu faciadan etkilenmemesini sa\u011flayan Prof. Dr. S\u00fcreyya Tahsin Ayg\u00fcn hocam\u0131z\u0131 sevgi, sayg\u0131 ve rahmetle an\u0131yorum.<\/strong><\/em><\/p>\n\n\n\n

Kaynak\u00e7a:<\/h2>\n\n\n\n
  1. Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease, https:\/\/doi.org\/10.1093\/toxsci\/kfr088<\/a><\/li>
  2. Thalidomide\u2010induced teratogenesis: History and mechanisms,https:\/\/doi.org\/10.1002\/bdrc.21096<\/a> <\/li>
  3. Braithwaite, Corporate Crime in the Pharmaceutical Industry, Abingdon, 1983 and 2013, p.68.<\/li>
  4. https:\/\/allthatsinteresting.com\/thalidomide-babies<\/a> <\/li>
  5. http:\/\/broughttolife.sciencemuseum.org.uk\/broughttolife\/themes\/controversies\/thalidomide<\/a> <\/li>
  6. https:\/\/corpus.nz\/chemical-legacies-thalidomide-in-new-zealand\/#_ednref2<\/a>
    <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Talidomid, 1950\u2019li y\u0131llar\u0131n sonunda Chemie-Grunenthal GmbH adl\u0131 Bat\u0131 Almanya\u2019da bulunan bir ila\u00e7 \u015firketi taraf\u0131ndan piyasaya sunuldu. \u0130lk ba\u015flarda etkili bir<\/p>\n","protected":false},"author":153,"featured_media":3181,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,25,6],"tags":[155,477,475,476,479,478,474,473],"acf":[],"views":4704,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/3177"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/153"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=3177"}],"version-history":[{"count":7,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/3177\/revisions"}],"predecessor-version":[{"id":3189,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/3177\/revisions\/3189"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/3181"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=3177"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=3177"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=3177"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}