Rheumatology, Vol 38, 24-32, Copyright © 1999 by British Society for Rheumatology
I Bjarnason and B Thjodleifsson
This overview includes theories and evaluation of non-steroidal anti-
inflammatory drug (NSAID)-induced gastrointestinal toxicity. Factors in
damage include microvascular aspects, neutrophil recruitment, mucosal
prostaglandins, gastrointestinal secretions and bacteria. We have proposed
an extensive simplified framework that includes an important local
initiating effect which may involve NSAID accumulation, interaction with
surface phospholipids, events that alter cellular ATP, and local/systemic
effects of cyclooxygenase (COX) inhibition. COX-2- selective drugs are
desirable not only because they spare COX-1 and so avoid gastrointestinal
toxicity, but also because COX-2-selective agents are only weakly acidic
and therefore avoid substantial accumulation in the gastric mucosa.
Short-term endoscopy studies of NSAIDs are important initially to evaluate
human gastroduodenal tolerability. They show that injury increases with the
amount of NSAIDs even though the lowest therapeutic doses inhibit gastric
COX almost completely, and that the more-acidic NSAIDs tend to cause
greater gastric damage. Long-term endoscopy studies involve NSAID ingestion
for at least 3 months. A main question is the extent to which the ulcers
seen cause symptoms, substantial bleeding and/or perforation. Measurement
of serious outcomes is thought by many to be the best assessment of
gastrointestinal safety, but studies find marked variations even with the
same drug. Damage to the small intestine by NSAIDs is even more frequent
than to the upper gastrointestinal tract, but is difficult to evaluate.
Conventional acidic NSAIDs increase the permeability of human small
intestine, probably by a non-prostaglandin mechanism, but nimesulide does
not do so, possibly because of its very weak acidity.
REVIEWS
Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs: the effect of nimesulide compared with naproxen on the human gastrointestinal tract
Department of Medicine, Guy's, King's and St Thomas' School of Medicine, London, UK.
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