GASTRIC-MUCOSAL DEFENSIVE FACTORS - THE THERAPEUTIC STRATEGY

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