1. INTRODUCTION
1.1 GENERAL CHARACTERISTICS OF CELECOXIB
Celecoxib is a non-steroidal anti-inflammatory drug, which was the first COX-2 inhibitor approved by the FDA. It is mainly used for the treatment of osteoarthritis, rheumatoid arthritis, and familial adenomatous polyposis. Celecoxib was primarily designed to decrease the risk of adverse gastrointestinal effects, but several reports of cardiovascular events expressed concerns about its use. Celecoxib has a moderate absorption rate, and peak absorption is observed after approximately two to four hours. The observed high distribution volume is a result of its low affinity for proteins. The defined daily dose of celecoxib is 200 mg, which patients must take for long-term pain management …show more content…
These two types of enzymes are responsible for the synthesis of prostaglandins. COX-1 is the most frequently expressed housekeeping isoenzyme, it provides gastric protection and keeps the vascular system in homeostasis. On the other hand, COX-2 is inducible, and is triggered when inflammation is started in the tissue.
Non-selective NSAIDs inhibit both isoenzymes, which may cause upper gastrointestinal adverse events, including ulceration, bleeding, and perforation. The purpose of developing a selective COX-2 inhibitor was to prevent these adverse effects. However, the disadvantage of selective inhibition of COX-2 is the loss of balance between pro-thrombotic and anti-thrombotic factors, resulting in additional cardiovascular side effects and an increase in major vascular events in comparison with non-selective NSAIDs.[2] Celecoxib has a potential selectivity ratio of more than …show more content…
Adenomas precede most cases of CRC, and are originated by several gene mutations.[6]
Previous research showed that the expression of COX-2 seems to be increased in CRC. It was proposed that the prostaglandins produced by COX-2 may be involved in regulating cellular proliferation, and potentially trigger the cascade of processes required for carcinogenesis, tumour growth and development. Thus, the use of celecoxib may be a significant approach to prevent and treat CRC, or even contribute to the reduction of the mortality rate. Even though the benefits seem promising, the long-term use of selective COX-2 inhibitors is contraindicated. Celecoxib may interfere with cardiovascular homeostasis by the concomitant inhibition of vascular COX-2 dependent PGI2 biosynthesis. Continuous systemic COX-2 inhibition is now widely accepted to increase the risk of a cardiovascular
1.1 GENERAL CHARACTERISTICS OF CELECOXIB
Celecoxib is a non-steroidal anti-inflammatory drug, which was the first COX-2 inhibitor approved by the FDA. It is mainly used for the treatment of osteoarthritis, rheumatoid arthritis, and familial adenomatous polyposis. Celecoxib was primarily designed to decrease the risk of adverse gastrointestinal effects, but several reports of cardiovascular events expressed concerns about its use. Celecoxib has a moderate absorption rate, and peak absorption is observed after approximately two to four hours. The observed high distribution volume is a result of its low affinity for proteins. The defined daily dose of celecoxib is 200 mg, which patients must take for long-term pain management …show more content…
These two types of enzymes are responsible for the synthesis of prostaglandins. COX-1 is the most frequently expressed housekeeping isoenzyme, it provides gastric protection and keeps the vascular system in homeostasis. On the other hand, COX-2 is inducible, and is triggered when inflammation is started in the tissue.
Non-selective NSAIDs inhibit both isoenzymes, which may cause upper gastrointestinal adverse events, including ulceration, bleeding, and perforation. The purpose of developing a selective COX-2 inhibitor was to prevent these adverse effects. However, the disadvantage of selective inhibition of COX-2 is the loss of balance between pro-thrombotic and anti-thrombotic factors, resulting in additional cardiovascular side effects and an increase in major vascular events in comparison with non-selective NSAIDs.[2] Celecoxib has a potential selectivity ratio of more than …show more content…
Adenomas precede most cases of CRC, and are originated by several gene mutations.[6]
Previous research showed that the expression of COX-2 seems to be increased in CRC. It was proposed that the prostaglandins produced by COX-2 may be involved in regulating cellular proliferation, and potentially trigger the cascade of processes required for carcinogenesis, tumour growth and development. Thus, the use of celecoxib may be a significant approach to prevent and treat CRC, or even contribute to the reduction of the mortality rate. Even though the benefits seem promising, the long-term use of selective COX-2 inhibitors is contraindicated. Celecoxib may interfere with cardiovascular homeostasis by the concomitant inhibition of vascular COX-2 dependent PGI2 biosynthesis. Continuous systemic COX-2 inhibition is now widely accepted to increase the risk of a cardiovascular