The therapeutic efficacy of misoprostol in peptic ulcer disease.

Misoprostol, a synthetic methyl ester analogue of prostaglandin E1 (PGE1) is both a powerful inhibitor of gastric secretion and is able to protect the gastroduodenal mucosa from damage produced by alcohol, aspirin, naproxen and tolmetin. The results of 12 double-blind, randomized, placebo- and cimetidine-controlled trials involving 4000 patients have been reviewed here and show that misoprostol, given in a dosage of 800 micrograms daily in two or four divided doses, is able to produce rates of complete ulcer healing and pain relief in both gastric and duodenal ulcer which are significantly superior to placebo therapy and comparable to those achieved with high or conventional doses of cimetidine. One further large trial has shown that misoprostol is able to heal a significant proportion of duodenal ulcers refractory to treatment with H2 receptor antagonists. In the compromised patient, two trials have suggested that misoprostol is able to abolish the adverse effects of smoking on duodenal ulcer, although this effect was not apparent in the gastric ulcer trials or in other duodenal ulcer trials. Similarly, while in volunteers pretreatment with misoprostol is able to protect the gastric mucosa from alcohol damage, there is little clinical evidence to support improved ulcer healing in the patient who abuses alcohol. Further studies in these areas should be conducted. Misoprostol could well have an important role to play in the protection of the gastroduodenal mucosa from damage produced by non-steroidal anti-inflammatory drugs (NSAIDs) in arthritic patients compelled to take these drugs for long periods. A series of double-blind placebo-controlled trials in healthy volunteers have shown that pretreatment with, or simultaneous administration of, 800 micrograms daily of misoprostol, reduces significantly mucosal damage produced by aspirin, tolmetin and naproxen. Two controlled clinical trials in a large number of arthritic patients have shown firstly, that misoprostol 800 micrograms daily is able to reduce significantly aspirin-induced mucosal bleeding as compared with placebo and secondly, in an endoscopically, placebo-controlled trial that it reduced significantly the frequency and severity of aspirin-induced mucosal lesions, accelerated the healing of erosions and ulcers and in other patients was able to protect the undamaged mucosa from injury. Misoprostol is well tolerated--a dose related, usually self limiting, diarrhoea occurred in a small proportion of patients but only rarely enforced withdrawal. Because of its uterotropic effects misoprostol should not be given to women of child bearing age unless they are taking adequate contraceptive measures. It has no other systemic effects and no clinically significant adverse haematology or biochemical abnormalities, or drug interactions have been reported. It does not seem to induce hypergastrinaemia. Misoprostol is, therefore, a safe and effective drug in the treatment of chronic peptic ulcer and could have a beneficial action in duodenal ulcers refractory to treatment with H2-receptor antagonists. It could benefit compromised groups of ulcer patients who are smokers or alcohol users amd certainly has been shown to protect the gastroduodenal mucosa against damage induced by NSAIDs in healthy volunteers and arthritic patients.

RCT Entities:   Population Interventions Outcomes