Introduction
Non-steroidal anti-inflammatory drugs are used in human and veterinary medicine to control pain and inflammation. Many commonly used NSAIDs, however, have serious adverse effects, including gastrointestinal ulcers, erosion, and perforation. Non-selective NSAIDs inhibit the activity of both cyclooxygenase isoforms: COX-1 and COX-2. COX-2 is primarily responsible for the inflammatory response, while COX-1 is constitutively expressed in most cells and is the dominant source of prostaglandins for gastric epithelial cytoprotection (Whittle et al., 1980). Thus, an NSAID which selectively reduces the activity of COX-2 while sparing the protective effects of COX-1 activity would be preferred. The coxib class of drugs selectively inhibit …show more content…
Cyclooxygenases, also known as prostaglandin-endoperoxide synthases, are enzymes involved in prostanoid synthesis. Prostanoids, a subclass of eicosanoids, include prostaglandins, thromboxanes, and prostacyclins. Generally speaking, prostaglandins are responsible for inflammatory reactions, thromboxanes are responsible for vasoconstriction, and prostacyclins are involved in the resolution phase of inflammation. Cyclooxygenase acts by adding two molecules of O2 to the middle of free fatty acid chains. This forms Prostaglandin G, a five-member carbon ring and two peroxide linkages. Prostaglandin H, the precursor for all other prostanoids, is then formed when one of the two peroxide linkages loses an oxygen. COX-2 can be selectivity inhibited due to a difference between the two isoforms at position 523: COX-1 has an isoleucine residue and COX-2 has a valine residue. The isoleucine residue is too large to allow for the formation of the hydrophobic side-pocket seen in COX-2. Coxib drugs bind to this site, thus selectively inhibit COX-2 (Kurumbail et al., 1996).
COX-1 and COX-2 have different roles within the body. COX-1 and COX-2 couple preferentially with thromboxane synthase and prostaglandin I synthase, respectively (Ricciotti and FitzGerald, 2011). COX-2 is induced by cytokines and tumor promoters and is involved in
Non-steroidal anti-inflammatory drugs are used in human and veterinary medicine to control pain and inflammation. Many commonly used NSAIDs, however, have serious adverse effects, including gastrointestinal ulcers, erosion, and perforation. Non-selective NSAIDs inhibit the activity of both cyclooxygenase isoforms: COX-1 and COX-2. COX-2 is primarily responsible for the inflammatory response, while COX-1 is constitutively expressed in most cells and is the dominant source of prostaglandins for gastric epithelial cytoprotection (Whittle et al., 1980). Thus, an NSAID which selectively reduces the activity of COX-2 while sparing the protective effects of COX-1 activity would be preferred. The coxib class of drugs selectively inhibit …show more content…
Cyclooxygenases, also known as prostaglandin-endoperoxide synthases, are enzymes involved in prostanoid synthesis. Prostanoids, a subclass of eicosanoids, include prostaglandins, thromboxanes, and prostacyclins. Generally speaking, prostaglandins are responsible for inflammatory reactions, thromboxanes are responsible for vasoconstriction, and prostacyclins are involved in the resolution phase of inflammation. Cyclooxygenase acts by adding two molecules of O2 to the middle of free fatty acid chains. This forms Prostaglandin G, a five-member carbon ring and two peroxide linkages. Prostaglandin H, the precursor for all other prostanoids, is then formed when one of the two peroxide linkages loses an oxygen. COX-2 can be selectivity inhibited due to a difference between the two isoforms at position 523: COX-1 has an isoleucine residue and COX-2 has a valine residue. The isoleucine residue is too large to allow for the formation of the hydrophobic side-pocket seen in COX-2. Coxib drugs bind to this site, thus selectively inhibit COX-2 (Kurumbail et al., 1996).
COX-1 and COX-2 have different roles within the body. COX-1 and COX-2 couple preferentially with thromboxane synthase and prostaglandin I synthase, respectively (Ricciotti and FitzGerald, 2011). COX-2 is induced by cytokines and tumor promoters and is involved in