|Commenced in January 2007||Frequency: Monthly||Edition: International||Paper Count: 2|
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.
Today COXIBs are used in the treatment of arthritis and many other painful conditions in selected patients with high gastrointestinal risk and low cardiovascular (CV) risk. Previously, we have identified an unexpected mechanism of action of a traditional non-steroidal anti-inflammatory drug (NSAID) (diclofenac) and a specific inhibitor of cyclooxygenase-2 (COXIB) (lumiracoxib) demonstrating that they possess weak competitive antagonism at the thromboxane receptor (TP). We hypothesize that modifying the structure of a known COXIB so that it becomes also a more potent TP antagonist will preserve the anti-inflammatory and gastrointestinal safety typical of COXIBs and prevent the CV risk associated with long term therapy.