The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti-inflammatory drugs.
Arachidonic acid is a polyunsaturated fatty acid covalently bound in esterified form in the cell membranes of most body cells. Following irritation or injury, arachidonic acid is released and oxygenated by enzyme systems leading to the formation of an important group of inflammatory mediators, the eicosanoids. It is now recognised that eicosanoid release is fundamental to the inflammatory process. For example, the prostaglandins and other prostanoids, products of the cyclooxygenase enzyme pathway, have potent inflammatory properties and prostaglandin E2 is readily detectable in equine acute inflammatory exudates. The administration of nonsteroidal anti-inflammatory drugs results in inhibition of prostaglandin synthesis and this explains the mode of action of agents such as phenylbutazone and flunixin. Lipoxygenase enzymes metabolise arachidonic acid to a group of noncyclised eicosanoids, the leukotrienes, some of which are also important inflammatory mediators. They are probably of particular importance in leucocyte-mediated aspects of chronic inflammation. Currently available non-steroidal anti-inflammatory drugs, however, do not inhibit lipoxygenase activity. In the light of recent evidence, the inflammatory process is re-examined and the important emerging roles of both cyclo-oxygenase and lipoxygenase derived eicosanoids are explored. The mode of action of current and future anti-inflammatory drugs offered to the equine clinician can be explained by their interference with arachidonic acid metabolism.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001777:Blood Coagulation; D002633:Chemotaxis; D003165:Complement System Proteins / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D006632:Histamine / Q000502:physiology; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006736:Horses; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D007705:Kinins / Q000502:physiology; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D010653:Phenylbutazone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D012701:Serotonin / Q000502:physiology
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D007705:Kinins; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid; D012701:Serotonin; D006632:Histamine; D003165:Complement System Proteins; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D010653:Phenylbutazone