Pharmacology

Eicosanoids

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  • Formed from arachidonic acid (via phospholipase action), a component of cell membrane phospholipids

  • Main types
    • Prostaglandins: subtypes
      • Prostacyclin: produced by endothelium and causes vasodilation and inhibition of thrombosis (aka prostaglandin I2)

      • Sensitise nerve endings to pain (but don’t produce pain)
    • Thromboxanes: vasoconstriction, platelet aggregation, bronchoconstriction
    • Leukotrienes: subtypes
      • Involved in allergic reactions and inflammation
      • Bronchoconstriction, vasoconstriction and increased vascular permeability
  • Initial rate-limiting step in their generation is mediated by phospholipase A2 or C
  • Free arachidonic acid is metabolised by
    • Cyclo-oxygenase: generating prostaglandins
      • Inflammatory prostaglandins are synthesised by COX-2 while gastroprotective prostaglandins are synthesised by COX-1

    • Lipoxygenase: generates leukotrienes
  • NSAIDs are cyclo-oxygenase inhibitors

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