Parasetamol ve siklooksijenaz enzim inhibisyonu

Parasetamol yuz yili askin suredir analjezik ve antipiretik olarak kullanilan guvenilir bir ilactir ancak parasetamolun etki mekanizmasi halen tam olarak anlasilamamistir. Her ne kadar siklooksijenaz (COX) enzim inhibisyonu da parasetamolun etki mekanizmasinda rol oynasa da ozellikle analjezik etki mekanizmasinda serotonerjik ve opioiderjik sistem gibi diger mekanizmalarin da katkisi artik iyi bilinmektedir. Antiinflamatuar etkisinin ise cesitli hayvan deneylerinde ve klinik arastirmalarda diger non-steroid antiinflamatuar ilaclara (NSAII) yaklastigi belirtilse de romatoid artrit gibi otoimmun hastaliklardaki inflamasyona karsi etkisiz olmasi onun diger NSAII’lar sinifindan ayri tutulmasini gerektirmistir. Parasetamol siklooksijenaz enzimini indirekt olarak inhibe eder. Bu inhibisyonun rolatif olarak yuksek peroksit varliginda ortadan kalktigi iddia edilmistir. Dusuk peroksit yogunlugunun oldugu merkezi sinir sisteminde (MSS) siklooksijenaz enzim inhibisyonunun analjezi ve antipiretik etki olusturdugu belirtilse de, peroksit yogunlugunun fazla oldugu trombosit ve immun hucrelerde ise etkisinin olmadigi ve bu yuzden parasetamolun romatoid artrit gibi yuksek peroxidaz aktivitenin gozlendigi hastaliklarda etkisiz oldugu iddia edilmistir. Ikibinli yillarin baslarinda yeni bir COX enzim varyanti kesfedilmis ve bunun COX-3 olarak adlandirilmasi parasetamolun etki mekanizmasinda bu enzimin rolunun olabilecegini dusundurmustur. Ancak yapilan calismalarda hem COX-3 enziminin tek basina ayri bir enzim hem de parasetamol ile etkilesiminin olup olmadigi netlik kazanmamistir. Bu derlemenin amaci parasetamolun COX enzim inhibisyonu uzerindeki etkileri konusunda okuyucuya bilgi vermektedir. Paracetamol and cyclooxygenase enzyme inhibition Parasetamol has been reliably used for over 100 years as analgesic and antipyretic but its mechanism of action is still not fully understood. Although the cyclooxygenase (COX) enzyme inhibition plays in one of the mechanisms of action of paracetamol, especially the contribution of other mechanisms, such as serotonergic and opioiderjik system is well known for the mechanism of analgesic effect today. By using various animal experimental models and clinical trials, it was reported that the antiinflammatory effect of paracetamol is nearly equivalent the other nonsteroid antiinflammatory drugs’ (NSAID); but due to its lacked effect in the autoinflammatory diseases such as rheumatoid artritis, it was reguired the paracetamol should be saperated from the other NSAIDs’ classification. Paracetamol indirectly inhibits the cyclooxygenase enzyme. This inhibition has been claimed to have disappeared in the presence of relatively high level of peroxide. Although it was shown that the inhibition of cyclooxigenase enzyme causes analgesic and antipyretic effect in central nervous ystem (CNS) that have a low peroxide activity, the lack of effect of paracetanole on the immune cells and trombocytes that have a high peroxide activity has been shown, thefore, it was claimed paracetamole had no effect in the diseases such as rheumatoid artritis which have a high peroxide activity. Since the beginning of 2000, a new COX enzyme variant was developed and it was thought that COX-3 may play a role in the mechanism of action of paracetamol. But in the studies, it is not clearly defined both the specifity of this enzyme and its interaction with the paracetamol. The purpose of this review is to give a knowledge about the effects of paracetamol on COX enzyme inhibition.