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This fascinating but simple and cheap drug has an assured future
Ask any medical student and he or she will tell you that aspirin reduces fever, pain, and inflammation but may cause ulcers. Students may also recollect that it prolongs bleeding, and may prevent strokes and heart attacks, but would be unlikely to know of its use in cancer or Alzheimer's disease.
A defining point in the history of aspirin was the discovery that it inhibited the prostaglandin forming cyclooxygenase. 1 Prostaglandins cause inflammation, fever, and pain; have gastric cytoprotective actions; and are implicated in platelet aggregation, so this discovery provided a unified explanation for the effects of aspirin (and most other non-steroidal anti-inflammatory drugs). However, events took an even more interesting turn when a further isoform of cyclo-oxygenase, cyclooxygenase-2, was discovered. 2 While similar in many ways to the original enzyme (COX 1) there were important differences, including the fact that COX 2 was induced in cells by inflammatory insults. COX 2 therefore seemed to be the most relevant target in inflammation, which led to the notion that the constitutive COX 1 generated prostaglandins required to maintain physiological functions (such as protection of the gastric mucosa, platelet aggregation) whereas COX 2 generated pro-inflammatory mediators. 3 Aspirin inhibited both isoforms, as did most non-steroidal anti-inflammatory drugs, perhaps explaining why these compounds were not only effective therapeutically but also had characteristic side effects.
The ensuing search by the pharmaceutical industry for selective COX 2 inhibitors culminated in the recent introduction of new, safer anti-inflammatory drugs as well as the rediscovery of older drugs that had COX 2 selective actions. But, as aspirin inhibits both isoforms, why does it continue to be used and why is there continuing interest in its pharmacology?
The answer to the first part of this...