Fig. 1. The arachidonic acid pathway.52–55,57,58,61 Corticosteroids exert their effect on the arachidonic acid pathway by inhibiting phospholipase A2. This action decreases the production of both the cyclo-oxygenase pathway and the lipoxygenase pathway products. Nonsteroidal anti-inflammatory drugs (NSAIDs) presently available usually inhibit the action of either prostaglandin synthetase or 5-lipoxygenase, or both of these enzymes. When both enzymes are inhibited by NSAIDs, the inhibition is usually unequal. Thus, NSAIDs may allow production of some of the arachidonic acid pathway products. This differential effect of NSAIDs on the cyclo-oxygenase and lipoxygenase pathways can shift the balance of the resulting arachidonic acid pathway products. For example, a cyclo-oxygenase inhibitor drug can shunt arachidonic acid away from the cyclo-oxygenase pathway and down the lipoxygenase pathway, resulting in larger amounts of lipoxygenase pathway products than would be seen in the absence of the drug.59,60 The cytochrome P450 pathway represents only a minor portion of the arachidonic acid metabolism. |