Blood Substitutes
Introduction
In September 2004, Merck (the manufacturer of Vioxx) announced a voluntary worldwide withdrawal of Vioxx because of an increased risk of heart attack and stroke.
Background on PGs and COX
In general, all Nonsteroidal anti-inflammatory drugs (NSAIDs) act as cyclooxygenase inhibitor (COX), it is an enzyme that catalyzes the formation of prostaglandins (PGs) from arachidonic acid. The first step in the synthesis of PGs is the release of the arachidonic acid from phospholipids in the cellular membrane, this reaction is catalyzed by the enzyme phospholipase A2, then two molecules of oxygen are added to arachidonic acid by the action of COX enzyme to form prostaglandin PGG2, then by the action of peroxidase, prostaglandin PGH2 will be formed, it is an unstable intermediate from which all other PGs such as PGE2 and PGI2(prostacyclin) and also thromboxane are derived by different enzymatic reactions.Prostaglandins (PGs) have significant role in both physiologic and pathologic processes. First, Some of the important physiological roles of PGs, PGE2 and PGI2 have significant roles in gastric mucosal protection in the presence of endogenous aggressive factor such as gastric acid by mainly increasing secretion of gastric mucosa and decreasing gastric acid secretion, also PGE2 has a role in regulating the kidney function by maintaining vascular tone, blood flow, and salt and water excretion. Moreover, there are important and opposing functions of both prostacyclin PGI2 and thromboxane TXA2 in maintaining the vascular homeostasis and good cardiovascular health, in detail, TXA2 is synthesised in the platelets by the action of COX-1 during the platelet activation, it increases platelet aggregation, vasoconstriction, and smooth muscle proliferation. In contrast, PGI2 is produced in the endothelial cells by the action of COX-2; it has a potent vasodilator and inhibits platelet aggregation and smooth muscle cell proliferation. Second, pathologically, the
In September 2004, Merck (the manufacturer of Vioxx) announced a voluntary worldwide withdrawal of Vioxx because of an increased risk of heart attack and stroke.
Background on PGs and COX
In general, all Nonsteroidal anti-inflammatory drugs (NSAIDs) act as cyclooxygenase inhibitor (COX), it is an enzyme that catalyzes the formation of prostaglandins (PGs) from arachidonic acid. The first step in the synthesis of PGs is the release of the arachidonic acid from phospholipids in the cellular membrane, this reaction is catalyzed by the enzyme phospholipase A2, then two molecules of oxygen are added to arachidonic acid by the action of COX enzyme to form prostaglandin PGG2, then by the action of peroxidase, prostaglandin PGH2 will be formed, it is an unstable intermediate from which all other PGs such as PGE2 and PGI2(prostacyclin) and also thromboxane are derived by different enzymatic reactions.Prostaglandins (PGs) have significant role in both physiologic and pathologic processes. First, Some of the important physiological roles of PGs, PGE2 and PGI2 have significant roles in gastric mucosal protection in the presence of endogenous aggressive factor such as gastric acid by mainly increasing secretion of gastric mucosa and decreasing gastric acid secretion, also PGE2 has a role in regulating the kidney function by maintaining vascular tone, blood flow, and salt and water excretion. Moreover, there are important and opposing functions of both prostacyclin PGI2 and thromboxane TXA2 in maintaining the vascular homeostasis and good cardiovascular health, in detail, TXA2 is synthesised in the platelets by the action of COX-1 during the platelet activation, it increases platelet aggregation, vasoconstriction, and smooth muscle proliferation. In contrast, PGI2 is produced in the endothelial cells by the action of COX-2; it has a potent vasodilator and inhibits platelet aggregation and smooth muscle cell proliferation. Second, pathologically, the
References: * Pharmacol Rev. 2004 Sep;56(3):387-437.Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition.Simmons DL, Botting RM, Hla T.