CORE FOUNDATIONS FOR MEDICINE TUTORIAL ON EICOSANOIDS

Drugs and Blood Clotting

Aspirin works by irreversibly inhibiting COX-1 and modifying the activity of COX-2

Low doses of aspirin (one children's tablet per day for an adult) irreversibly inhibits COX-1.
  • In most cells one aspirin/day has no long term effect on COX-1. This is because COX-1 has a short half-life and is continually being synthesized.
  • In platelets, one aspirin/day does have a long term effect on COX-1. This is because platelets have no nucleus and do not synthesize new COX-1.
  • At low doses, aspirin has little effect on COX-2.
Aspirin's ability to reduce pain, fever and inflammation at moderate to high doses, is due to modification of COX-2 as well as COX-1.
  • Pain, fever and inflammation are mediated by PGD and PGE, and in most cells, COX-2 is the major producer of PGD and PGE.
  • COX-2 synthesis is induced by conditions that lead to pain fever and inflammation, making it the predominant cycloogygenase under these conditions.
  • When modified by aspirin, COX-2 does not make prostaglandins (e.g. PGD and PGE). Instead, it makes anti-inflamatory eicosanoids that you will meet in later screens.

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