Prostaglandins and the mechanism of action of anti-inflammatory drugs.
Aspirin and a large number of nonsteroidal anti-inflammatory drugs act primarily through the inhibition of prostaglandin synthesis by inhibiting the enzyme cyclooxygenase. Other groups of biologically active polyunsaturated fatty acid derivatives including the leukotrienes, are generally not inhibited by this class of drugs in the same concentration ranges. Inhibition of the vasodilator prostaglandins, prostaglandin E2 and prostacyclin, as well as the leukotrienes, may reduce their inflammatory effects in several disease states. In addition, prostaglandin synthesis is also inhibited by glucocorticoids even though their mode of action may involve other effects as well. Prostaglandin E2 stimulates the osteoclastic reabsorption of juxtaarticular bone; its inhibition by nonsteroidal anti-inflammatory agents may, therefore, retard the process of bone erosion in rheumatoid arthritis and in other inflammatory processes. Inhibition of prostaglandin synthesis by these drugs accounts for many of their major toxic effects, including gastritis, which is the most common side effect; precipitation or aggravation of renal failure; fluid retention; hyperkalemia; antiplatelet effects with hemorrhagic phenomena; and aggravation of asthma and rhinosinusitis. Inhibition of prostaglandin synthesis can, therefore, account for most of the therapeutic as well as toxic effects of the nonsteroidal anti-inflammatory agents. Inhibition of pathways of synthesis of other important mediators, such as leukotrienes, are currently under investigation and may provide another approach for the development of new therapeutic agents.
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004064:Digestive System / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects; D011247:Pregnancy; D011448:Prostaglandin Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000502:physiology; D012137:Respiratory System / Q000187:drug effects; D013189:SRS-A / Q000096:biosynthesis / Q000502:physiology
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D013189:SRS-A