{"id":522,"date":"2017-05-16T19:00:20","date_gmt":"2017-05-16T16:00:20","guid":{"rendered":"https:\/\/tatd.org.tr\/tatdtoks\/2021\/09\/17\/bir-antidot-olarak-glukagon-efsanesi\/"},"modified":"2021-11-10T22:35:24","modified_gmt":"2021-11-10T19:35:24","slug":"bir-antidot-olarak-glukagon-efsanesi","status":"publish","type":"post","link":"https:\/\/tatd.org.tr\/toksikoloji\/2017\/05\/16\/bir-antidot-olarak-glukagon-efsanesi\/","title":{"rendered":"Bir Antidot Olarak \u201cGlukagon\u201d Efsanesi"},"content":{"rendered":"<p>Farmakolojik dozlarda uyguland\u0131\u011f\u0131nda; ins\u00fclin, katekolaminler ve kalsitonin\u00a0 sekresyonuna neden olur.<\/p>\n<p>Primer olarak karaci\u011ferde metabolize olur, renal yolla ve plazmada inaktive edilir. Etki ba\u015flama zaman\u0131 iv uygulamada 5-20 dk, im uygulamada 30 dk ve sc uygulamada 30-45 dk\u2019d\u0131r. Eliminasyon yar\u0131-\u00f6mr\u00fc plazmada iv uygulamada 8-18 dk ve im uygulamada 26-45 dk \u2019d\u0131r. Yar\u0131-\u00f6mr\u00fc k\u0131sa oldu\u011fu i\u00e7in etkisinin devam\u0131nda inf\u00fczyona gerek vard\u0131r. Bulant\u0131, kusma ve hiperglisemi gibi yan etkileri s\u0131kt\u0131r.<\/p>\n<p style=\"text-align: center\"><img decoding=\"async\" style=\"height: 223px;width: 400px\" src=\"https:\/\/tatd.org.tr\/tatdtoks\/wp-content\/uploads\/sites\/36\/2021\/10\/beta_blocker-2.jpg\" alt=\"\" \/><\/p>\n<p>Eri\u015fkinlerde Beta bloker (BB) yada kalsiyum kanal bloker (KKB) zehirlenmesinde tedavide 5 mg iv bolus verilir, etki g\u00f6stermezse 5 dk sonra ayn\u0131 doz tekrarlan\u0131r. Klinik yan\u0131t olursa (nab\u0131z ve tansiyonda art\u0131\u015f) 2-5 mg\/sa %5 dekstroz i\u00e7inde\u00a0 inf\u00fczyona ge\u00e7ilir. 10 mg da klinik yan\u0131t g\u00f6r\u00fclmezse uygulamadan vazge\u00e7ilir. \u00c7ocuklarda ba\u015flang\u0131\u00e7 dozu 30-150 mcg\/kg bolus ve takiben 70 mcg\/kg (max 5mg\/sa) inf\u00fczyon dozu \u015feklinde uygulan\u0131r. Ama\u00e7 ortalama arteriel bas\u0131nc\u0131 60 mmHg da tutmakt\u0131r. Bu sa\u011flanamazsa ek tedaviler uygulan\u0131r.<\/p>\n<p><img decoding=\"async\" style=\"float: right;height: 225px;margin-left: 5px;margin-right: 5px;width: 300px\" src=\"https:\/\/tatd.org.tr\/tatdtoks\/wp-content\/uploads\/sites\/36\/2021\/10\/glucagon-2.jpg\" alt=\"\" \/>Glukagon, geleneksel olarak BB zehirlenmesinde tedavide kullan\u0131lan bir antidottur.\u00a0 Ayn\u0131 zamanda KKB zehirlenmesinde de kullan\u0131l\u0131r.<\/p>\n<p>Ancak glukagonun antidot olarak kullan\u0131m\u0131n\u0131 k\u0131s\u0131tlayan baz\u0131 nedenler vard\u0131r;<\/p>\n<ul>\n<li>Etkinli\u011fine dair yeterince kan\u0131t yoktur.<\/li>\n<li>Ortalama arteriel bas\u0131n\u00e7ta de\u011fi\u015fiklik yapmaz.<\/li>\n<li>S\u0131k\u00e7a kusmaya neden olur ve aspirasyon sonucu havayolu i\u00e7in risk olu\u015fturur.<\/li>\n<li>Y\u00fcksek doz ins\u00fclin yada\u00a0 di\u011fer destek tedavilerin verilmesinde gecikmeye yol a\u00e7ar.<\/li>\n<\/ul>\n<p>Toksikolojide antidot olarak glukagon kullan\u0131m\u0131n\u0131n kan\u0131tsal temeli eksiktir. Bu konuda randomize kontroll\u00fc klinik \u00e7al\u0131\u015fma yap\u0131lmas\u0131 etik olmad\u0131\u011f\u0131 i\u00e7in, genellikle olgu sunumlar\u0131na dayal\u0131 pratik deneyimler s\u00f6z konusudur. Glukagon, adenil siklaz\u0131 aktive ederek g\u00f6sterdi\u011fi inotrop ve kronotrop etkisi nedeniyle BB zehirlenmesinde kullan\u0131l\u0131r.<\/p>\n<p>1960\u2019 da Farah ve Tuttle hayvanlarda katekolamin benzeri etkileri oldu\u011funu ve bu etkilerin propranolol ile bloke edilemedi\u011fini g\u00f6sterdiler. 1968\u2019 de Glick ve ark ve Luchessi\u00a0 ise glukagonun BB antidotu olarak kullan\u0131m\u0131n\u0131 \u00f6nerdiler.<\/p>\n<p>BB zehirlenmesinde; glukagon kalp h\u0131z\u0131n\u0131 art\u0131r\u0131rken, ortalama arteriyel bas\u0131n\u00e7ta minimal de\u011fi\u015fiklik yapar yada de\u011fi\u015fiklik yapmaz. KKB zehirlenmesinde; kalp h\u0131z\u0131n\u0131 art\u0131r\u0131rken, ortalama arteriyel bas\u0131n\u00e7ta de\u011fi\u015fiklik yapmaz. Hayvan \u00e7al\u0131\u015fmalar\u0131nda de\u011fi\u015fik dozlarda kullan\u0131lan glukagonun hayatta kal\u0131ma olumlu bir etkisi g\u00f6sterilememi\u015f olup, kalp h\u0131z\u0131n\u0131 ge\u00e7ici olarak art\u0131rd\u0131\u011f\u0131 ve ortalama arteriel bas\u0131n\u00e7 \u00fczerine etkisinin minimum oldu\u011fu g\u00f6sterilmi\u015ftir.<\/p>\n<p>BB yada KKB zehirlenmesinde glukagonun etkinli\u011fini de\u011ferlendiren insan \u00e7al\u0131\u015fmas\u0131 bulunmamaktad\u0131r, \u00e7ok say\u0131da olgu bildirimleri vard\u0131r. BB (Propranolol) ile ilgili ilk olgu bildirimi 1971\u2019de NEJM\u2019de ve KKB (Verapamil) ilgili ilk olgu bildirimi ise 1982\u2019de Lancet\u2019de yay\u0131mlanm\u0131\u015ft\u0131r.<\/p>\n<p>\u0130lgin\u00e7 olarak nerdeyse\u00a0 t\u00fcm \u00e7al\u0131\u015fmalarda KKB zehirlenmesinde kullan\u0131lan rekombinan glukagon preperat\u0131 olup, memeli pankreas\u0131ndaki pancreas h\u00fccrelerinden elde edilen bu preperat ins\u00fclin i\u00e7ermekteydi. Dolay\u0131s\u0131yla bu yararl\u0131 etkinin ins\u00fclinden kaynaklan\u0131yor olmas\u0131 muhtemeldir.<\/p>\n<p>Sonu\u00e7 olarak; bir antidot olarak glukagonun etkinli\u011fiyle ilgili yeterince kan\u0131t yoktur, nispeten pahal\u0131 bir ila\u00e7 oldu\u011fu i\u00e7in \u00e7ok y\u00fcksek dozlarda kullan\u0131m\u0131 gerekmekte ve bu a\u00e7\u0131dan \u00e7o\u011funlukla hastane stoklar\u0131 yetersiz kalabilmektedir. Doz ba\u011f\u0131ml\u0131 olarak bulant\u0131-kusmaya neden olabilmektedir ve son olarak g\u00fcn\u00fcm\u00fczde y\u00fcksek doz ins\u00fclin tedavisi \u00e7o\u011fu toksikolog taraf\u0131ndan daha \u00e7ok tercih edilmektedir. BB zehirlenmelerinde ikinci basamak tedavide d\u00fc\u015f\u00fcn\u00fclebilir. Genellikle glukagon tek ajan olarak kullan\u0131ld\u0131\u011f\u0131nda sonu\u00e7lar ba\u015far\u0131s\u0131z olmakta ve di\u011fer ek tedavi y\u00f6ntemlerine gerek duyulmaktad\u0131r.<\/p>\n<h2><em>Kaynaklar<\/em><\/h2>\n<ol>\n<li><a href=\"https:\/\/lifeinthefastlane.com\/ccc\/glucagon-as-an-antidote\/\"><em>https:\/\/lifeinthefastlane.com\/ccc\/glucagon-as-an-antidote\/<\/em><\/a><\/li>\n<li><a href=\"https:\/\/lifeinthefastlane.com\/ccc\/glucagon-therapy\/\"><em>https:\/\/lifeinthefastlane.com\/ccc\/glucagon-therapy\/<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.uptodate.com\/contents\/glucagon-drug-information?source=preview&amp;anchor=F25474760#F25474760\"><em>https:\/\/www.uptodate.com\/contents\/glucagon-drug-information?source=preview&amp;anchor=F25474760#F25474760<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.uptodate.com\/contents\/beta-blocker-poisoning?source=search_result&amp;search=glucagon&amp;selectedTitle=9~150\"><em>https:\/\/www.uptodate.com\/contents\/beta-blocker-poisoning?source=search_result&amp;search=glucagon&amp;selectedTitle=9~150<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Graudins%20A%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=26344579\"><em>Graudins A<\/em><\/a><em>, <\/em><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Lee%20HM%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=26344579\"><em>Lee HM<\/em><\/a><em>, <\/em><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Druda%20D%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=26344579\"><em>Druda D<\/em><\/a><em>. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2016 Mar;81(3):453-61. doi: 10.1111\/bcp.12763. Epub 2015 Oct 30.<\/em><\/li>\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Bailey%20B%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=14514004\"><em>Bailey B<\/em><\/a><em>. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol. 2003;41(5):595-602.<\/em><\/li>\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Truitt%20CA%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=22311669\"><em>Truitt CA<\/em><\/a><em>, <\/em><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Brooks%20DE%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=22311669\"><em>Brooks DE<\/em><\/a><em>, <\/em><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Dommer%20P%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=22311669\"><em>Dommer P<\/em><\/a><em>, <\/em><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=LoVecchio%20F%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=22311669\"><em>LoVecchio F<\/em><\/a><em>. Outcomes of unintentional beta-blocker or calcium channel blocker overdoses: a retrospective review of poison center data. J Med Toxicol. 2012 Jun;8(2):135-9. doi: 10.1007\/s13181-011-0209-8.<\/em><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p><em>Do\u00e7. Dr. \u00d6zlem K\u00f6ksal<\/em><\/p>\n<p>Glukagon; pankreas\u0131n alfa h\u00fccrelerinden sal\u0131nan polipeptit yap\u0131da bir hormon olup, beta adrenerjik ajanlardan ba\u011f\u0131ms\u0131z olarak adenil siklaz\u0131 aktive ederek cAMP\u2019yi art\u0131r\u0131r. <\/p>\n","protected":false},"author":1589,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[10014],"tags":[83,164,214,342],"class_list":["post-522","post","type-post","status-publish","format-standard","hentry","category-akademik-blog-yazisi","tag-beta-bloker","tag-glukagon","tag-kalsiyum-kanal-bloker","tag-polipeptit"],"acf":[],"_links":{"self":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/522","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/users\/1589"}],"replies":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/comments?post=522"}],"version-history":[{"count":0,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/522\/revisions"}],"wp:attachment":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media?parent=522"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/categories?post=522"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/tags?post=522"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}