A hundred years after the introduction of aspirin as the first effecti
ve anti-inflammatory drug, problems of tolerability still beset this c
lass of drugs, in particular, gastrointestinal toxicity, Despite this,
NSAIDs are among the most widely used and prescribed drugs world-wide
, Many agents have been used to counteract these side-effects with var
ying degrees of success and acceptance, Although the central mechanism
of NSAID action, reduced prostaglandin production by cyclooxygenase (
COX) inhibition, was first described 25 years ago, the recent discover
y of a second, inducible form of cyclooxygenase, COX-2, has stimulated
research and interest in producing NSAIDs that are inherently safer w
hilst maintaining efficacy. Specific COX-2 inhibitors, the first of wh
ich has recently been marketed in the UK, offer real hope as safer NSA
IDs and this may be realised when drugs with even greater specificity
become available, However, long-term safety and efficacy need to be de
monstrated in clinical practice, and questions remain unanswered about
possible physiological roles for COX-2. Other approaches to improving
the safety of NSAIDs, including profound acid suppression and nitric
oxide donation, may prove to be as successful in this rapidly changing
field.