Eksenatid Kullanımının Toksikolojik Açıdan Değerlendirilmesi

Year 2012, Issue: 2, 159 - 178, 01.06.2012

Pınar Erkekoğlu Belma Koçer Gümüşel Gönül Şahin

Abstract

Diabetes mellitus vücudun yeteri kadar insülin üretememesi Tip 1 veya üretilen insüline yeteri kadar yanıt verememesi Tip 2 ile ortaya çıkan ve yüksek kan şekeri ile kendini gösteren bir hastalıktır. İnsülin, pankreasta üretilen ve vücudun glikozu absorplamasını ve enerjiye dönüştürmesini sağlayan bir hormondur ve tip 2 diabette insülin rezistansı söz konusudur. Glukagon benzeri peptit analogları, glukagon benzeri peptit-1 GLP-1 reseptörüne bağlanarak, pankreas β-hücrelerinden insülin salımını artıran ilaçlardır. Endojen GLP-1’nin yarı ömrü çok kısa olduğu için GLP-1 analogları yerine GLP-1 agonistleri uzun yarı ömürleri ile uzun süre insülin salımını sağladıkları için ilaç olarak geliştirilmişlerdir. Eksenatid tip 2 diyabette kullanımı onaylanmış bir GLP reseptör agonisti ve “inkretinmimetik”idir ve oral antidiyabetiklerle tedavi edilemeyen diyabetin tedavisinde önerilmektedir. Etki mekanizması tam olarak bilinmemekle birlikte, pankreatik β-hücrelerinden akut glikoz-bağımlı insülin salımını artırarak açlık ve postprandiyel glisemik kontrolü sağlayan ve gastrik boşalmayı geciktirerek erken tokluk hissini sağlayarak etki gösteren bir ilaçtır. Ayrıca artmış glukagon salımını azaltmaktadır. Ancak ilacın mide boşalma zamanı üzerindeki geciktirici etkisinin bulantı ve kusma gibi ters etkileri beraberinde getirebileceği dikkate alınmalıdır. Diğer taraftan, ilacın neden olabileceği farklı tiplerde pankreatitin hayatı tehdit eden önemli bir hastalık olduğu unutulmamalıdır. İlaç başta hassas popülasyonlar olmak üzere hekim kontrolünde dikkatli bir şekilde kullanılması gerekmektedir. Konu ile ilgili çelişkili hususların kesinleşebilmesi için kapsamlı izleme çalışmaları ve güvenilir geribildirimlerin alınıp değerlendirilmesi gerekmektedir. Bu derlemede eksenatidin toksikolojik profilinden bahsedilecektir ve ilacın farmako/toksiko-kinetiği ve dinamiği, ters etkileri, ilaç etkileşmeleri ve pankreatitle olan ilişkisi değerlendirilecektir.

Keywords

Eksenatid, tip 2 diabet, glukagon benzeri peptit analogları, GLP-1 agonistleri

Toxicological Evaluation of Exenatide Usage

Abstract

Diabetes mellitus is a disease in which a person has a high blood glucose level as a result of the body’s either not producing enough insulin type 1 , or because body cells do not properly respond or are resistant to the insulin that is produced type 2 . Insulin is synthesized in pancreas; it is responsible for the absorption and conversion of glucose to energy. Glucagon-like peptide analogues are drugs that bind to glucagon- like peptide-1 GLP-1 receptor and enhance insulin secretion from pancreatic β-cells. As the half-life of GLP-1 is very short, instead of GLP-1 analogues, GLP-1 agonists with long half-lives are developed to provide longer duration of insulin secretion. Exenatide is an approved GLP-1 agonist and “incretinmimetic” used in type 2 diabetes and is suggested in diabetes that cannot be treated with oral antidiabetics. Though its mode of action is not clear, it is a drug that controls fasting and postprandial glycemia by increasing glucose-dependent insulin secretion from pancreatic β-cells and enables satiety in shorter period. However, the drug prolongs the gastric emptying time and this brings the side effects nausea and vomiting in turn. On the other hand, it should not be forgotten that the drug causes different types of pancreatitis which is a serious lifethreatening disease. The drug must be used with caution by prescription. Comprehensive surveillance studies and reliable feedbacks are needed to evaluate the clarification of contradictory issues in the usage of this particular drug. This review will focus on the toxicological profile of exenatide: pharmaco/toxico-kinetics and dynamics, safety/efficacy, adverse reactions, drug interactions and its relationship with pancreatitis.

Keywords

Exenatide, type 2 diabetes, glucagon-like peptide analogues, GLP-1 agonists

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