The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti‐inflammatory drugs

Abstract

Summary 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 cyclo‐oxygenase 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 non‐cyclised 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 antiinflammatory 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 antiinflammatory drugs offered to the equine clinician can be explained by their interference with arachidonic acid metabolism.

Effect of Ginger Constituents and Synthetic Analogues on Cyclooxygenase-2 Enzyme in Intact Cells

“…Activation of COX results in the synthesis of a wide spectrum of prostaglandins (PGs) (5,6), the critical mediators of the inflammatory process, with various activities leading to increased vascular permeability, increased vasodilation and induction of neutrophil chemotaxis (6).…”

Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy

“…These negative factors associated with opioid use have resulted in the prominence of NSAIDs in providing perioperative analgesia 31 . Despite the desirable analgesic effects of NSAIDs, their use is associated with inhibition of prostaglandin production and disruption of the processes they participate in, resulting principally in various degrees of renal function impairment and gastrointestinal irritation and ulceration 13,24 . Other adverse effects of NSAIDs include coagulopathy, liver damage and worsening of cardiac failure 19 .…”

Efficacy and adverse effects of joint medication in the horse – A review of the literature – Part 1: Conventional joint medication and the risks involved with joint injection in the horse

“…Dieses an der Colorado State University (CSU) entwickelte In vivo-Modell wurde zunächst mit verschiedenen Corticosteroiden durchgeführt und ist heute wohl das bekannteste Standardmodell zur Evaluierung der Wirksamkeit aller gängigen Gelenkbehandlungen beim Pferd (Nixon et al 1992). Die Zellkulturen können als Monolage oder dreidimensional, beispielsweise in Form von Chondrozytenpellets angelegt sein (Frean et al 1997, Schaefer et al 2009 (Higgins und Lees 1984, Di Rosa 1985, Pelletier et al 1995, Coughlan et al 1998, Richardson und Dodge 2003, Busschers et al 2010, Garvican et al 2010 (Wright et al 1986, Schimmer und Parker 1995, Yarbrough 2004). …”

“…SMOADs wie NSAIDs (non steroidal anti inflammatory drugs) beeinflussen hauptsächlich die Schmerzsymptomatik und die Gelenkentzündung (Michon et al 2010). Im Gegensatz dazu soll sich die Applikation von DMOADs, wie Hyaluronsäure oder PSGAG (Polysulfatiertes Glykosaminoglykan), positiv auf die Knorpelsubstanz und synoviale Strukturen auswirken (chondroprotektive Therapeutika) (Higgins und Lees 1984, Di Rosa 1985, Goldberg und Buckwalter 2005, Frisbie et al 2009a. Moderne Therapieansätze, wie zum Beispiel die Gentherapie, lassen sich beiden Gruppen zuordnen (Frisbie et al 2002).…”