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STATE THE POSSIBLE DRUG TARGETS IN INFLAMMATORY DISEASE 1

STATE THE POSSIBLE DRUG TARGETS IN INFLAMMATORY DISEASE
1. Cyclo-oxygenase inhibitors (COX inhibitors)
the drugs have the following effects:
Anti inflammatory action: they provide symptomatic relief from pain and swelling in chronic joint disease i.e. in osteo-arthritis and rheumatoid arthritis. They decrease prostaglandin E2 and prostacyclin reduces vasodilation and, indirectly, oedema. However, the inflammatory cells are not directly reduced.
Analgesic action: it reduces headaches by decreasing prostaglandin mediated vasodilation. This is through the reduction of prostaglandin generation making the nociceptive nerve endings less sensitive to inflammatory mediators like bradykinins and 5-hydroxytryptamine.
Antipyretic action: NSAIDs prevent the release of prostaglandins from interleukin-1 in the central nervous system. This reduces the hypothalamic set point for temperature control, thereby reducing fever.
Examples of NSAIDs are:- aspirin, ibuprofen, naproxen, indomethacin, piroxicam.
Many NSAID’s have different functions and composition but they primarily target fatty acid COX enzymes and thereby inhibiting the production of prostaglandins and thromboxanes. Other functions of NSAID’s in inflammatory effects are:
• Inhibition of vasodilation and oedema to reduce peripheral COX-2-generated prostaglandin synthesis
• Reduce harmful superoxide free radical generation by neutrophils and macrophages
• Uncouple G-protein regulated processes in the cell membrane of inflammatory cells. This reduces their responsiveness to some agonists released by damaged tissue
Explain the newer drug targets in inflammation stating in which way they are better than the conventional medication used in inflammatory disorders.
COX-2 SELETIVE INHIBITORS (newer anti-inflammatory drugs)
Examples of such are:
• Celecoxib
• Etoricoxib
• Parecoxib

Selective COX-2 inhibitors have anti-inflammatory actions similar to conventional NSAIDs but they may be less effective analgesics (due to less inhibition of COX-3 in the brain and spinal cord).
Selective COX-2 have little direct effect on platelet TXA2 production and do not impair platelet aggregation. However, they suppress the production of anti-aggregatory and vasodilator PGI2 by blood vessels, which may allow TXA2 to exert unopposed aggregatory effects on platelets.

Selective COX-2 inhibitors interact with PPARs and impair macrophage activity and T-cell-mediated immune responses
In 2012, Rang H.P. discovered that “Celecoxib and etoricoxib are well absorbed from the gut, enabling them to have less gastrointestinal toxicity and are eliminated by hepatic metabolism. A conventional drug i.e. aspirin, causes local damage to the gastric mucosa” (Rang & Dale 2012, p.325)