Review

Rheumatology International

, Volume 2, Issue 1, pp 1-10

An analysis of the gastro-intestinal side-effects of non-steroidal anti-inflammatory drugs, with particular reference to comparative studies in man and laboratory species

  • K. D. RainsfordAffiliated withLilly Research Centre Ltd.

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Summary

A critical analysis has been performed of reports published on the incidence of gastro-intestinal (GI) side-effects found in arthritic patients being treated with non-steroid anti-inflammatory (NSAI) drugs. The results show the following:
  1. 1.

    The incidence of GI ulceration (as revealed by gastroscopy) and haemorhage in arthritic patients taking NSAI drugs may be higher than suspected from clinical trial data.

     
  2. 2.

    Incidence of all GI side-effects (including ulceration and haemorrhage) may be lower with some of the new NSAI drugs than with traditional drugs (e.g. aspirin, indomethacin and phenylbutazone).

     
  3. 3.

    Arthritic patients may be more susceptible to the ulcerogenic actions of NSAI drugs. Experiments with animals, together with evidence from clinical studies, indicate that stress factors and the presence of decreased mucosal resistance in the diseased state may contribute to the enhanced susceptibility of the GI tract towards the ulcerogenicity of NSAI drugs.

     
  4. 4.

    Comparison of data on gastroscopic observations in man with the author's data on the effects of NSAI drugs in stress-sensitized rats shows the latter technique appears to be a useful means of predicting the ulcerogenic potential of NSAI drugs in man. The comparison has also been used to predict the ulcerogenicity of drug — alcohol combinations; alcohol being a common ulcerogen consumed by many patients. Some NSAI drugs with low ulcerogenic activity (i.e. azapropazone, benoxaprofen and fenclofenac) in the stressed-rat assay show little or no interaction with alcohol.

     

These studies using laboratory animals show the importance of employing conditions to mimic environmental factors (e.g. stress and alcohol consumption) which might predispose individuals to ulcerogenic or other side-effects of NSAI drugs. From these studies it appears possible to construct ‘predictive profiles’ of the relative ulcerogenicity of NSAI drugs which may be applicable to the clinical situation in man.

Key words

Gastric mucosa Aspirin Stress Antiinflammatory drugs Arthritis