Effect of diclofenac sodium on the arachidonic acid cascade.
The anti-inflammatory activity of nonsteroidal anti-inflammatory drugs is primarily attributed to inhibition of distinct steps in the arachidonic acid cascade, particularly, the cyclo-oxygenase pathway. Diclofenac sodium, a compound of this class of drugs, appears to have a dual effect since it also regulates the lipoxygenase pathway. Study of appropriate cell systems (leukocytes and whole blood in rats) demonstrates that diclofenac's potent inhibition of cyclo-oxygenase activity causes a sharp reduction in the formation of prostaglandin, prostacyclin, and thromboxane products, all key mediators of inflammation. Recent work discloses that at higher concentrations, diclofenac sodium also reduces the formation of products of the lipoxygenase pathway (5-hydroxyeicosatetraenoic acid, leukotrienes). The mechanism by which this evolves, however, appears to be unrelated to direct inhibition of lipoxygenase. Instead, by enhancing its reincorporation into triglycerides, diclofenac sodium reduces the intracellular level of free arachidonic acid.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000032:analysis / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007052:Ibuprofen / Q000494:pharmacology; D007962:Leukocytes / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology; D010743:Phospholipids / Q000032:analysis; D010894:Piroxicam; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D013189:SRS-A / Q000096:biosynthesis; D013843:Thiazines / Q000494:pharmacology; D014280:Triglycerides / Q000032:analysis
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D010743:Phospholipids; D011458:Prostaglandins E; D013189:SRS-A; D013843:Thiazines; D014280:Triglycerides; D010894:Piroxicam; D004008:Diclofenac; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D009288:Naproxen; D015121:6-Ketoprostaglandin F1 alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001091:Arachidonate Lipoxygenases; D015232:Dinoprostone; D007052:Ibuprofen