Non-steroidal anti-inflammatory drugs (
NSAIDs) such as
aspirin exert
irritant and toxic effects upon the organs of the gastrointestinal tract.
NSAID toxicity in the gastrointestinal tract is related, at least in part, to the inhibition of the
cyclo-oxygenase (COX)
enzyme, leading to a reduction of 'cytoprotective'
prostaglandin synthesis. In this paper, examples in which
NSAIDs exert beneficial effects in the gastrointestinal tract are discussed.
NSAIDs, particularly
aspirin, are showing promise in the
chemoprevention of colorectal, and, to a lesser degree, oesophageal
cancers. The clinical value of
NSAIDs in the treatment of established
gastrointestinal tract cancers is also worthy of further study. There is good clinical evidence showing the value of
diclofenac for the treatment of biliary
colic and
aspirin or
ibuprofen for the prevention of
gallstones.
NSAIDs also have therapeutic potential against other inflammatory
gastrointestinal diseases in the oesophagus and possibly pancreas and liver. To a lesser degree, there is some evidence that
NSAIDs may have a therapeutic potential in certain gastrointestinal motility disorders, such as
aspirin in the post-irradiation syndrome. It therefore follows that in these cancerous, inflammatory and motility pathologies,
prostaglandins exert deleterious effects. The paradox of
prostaglandins being 'cytoprotective' and potentially damaging can be explained by considering the enzymic origin of
prostaglandins. COX-1 is expressed physiologically while inducible COX-2 is expressed in pathological situations. The beneficial clinical effects of selective COX-2-inhibiting
NSAIDs in the gastrointestinal tract deserve further study. This paper challenges the concept of 'cytoprotection'.