Gastric mucosal defensive factors: the therapeutic strategy.

There are several interesting approaches to augmenting defence or repair mechanisms that can be used already or may find a place in therapy for ulcer disease. Factors such as epidermal growth factor and basic fibroblast growth factor show potential. Alternative strategies might be to stimulate mucosal blood flow with agents that release nitric oxide (NO), or to scavenge free radicals in the inflamed or ischaemic mucosa. If such approaches are to find a role in therapy, it is likely that it will be restricted: perhaps for the treatment of refractory ulcers, or for prophylaxis of stress ulceration. This is because most ulcers in future are likely to be healed with tolerable and high efficacy acid-inhibiting drugs then have their recurrence prevented by regimens that eradicate Helicobacter pylori. The most important current indication for concentrating on enhancing mucosal defences is for managing non-steroidal anti-inflammatory drug (NSAID)-induced ulcers. There is no clear advantage in using a defence-enhancing agent (rather than an acid suppressant) to heal an NSAID ulcer if the NSAID can be stopped. The main value of prostaglandins is for prophylaxis of NSAID ulcers in those patients who need ongoing treatment with NSAID. For cost-benefit reasons, prostaglandins should probably be used mainly for those at high risk of NSAID complications, and there has been progress in identifying these. Another interesting approach is aimed at clarifying mechanisms of gastric adaptation to NSAID, so that we might be able to design drugs and dosing regimens to maximize this phenomenon.