Drugs

, Volume 25, Issue 3, pp 315–330 | Cite as

Newer Antisecretory Agents for Peptic Ulcer

  • K. W. Somerville
  • M. J. S. Langman
Review Article

Summary

Although cimetidine is a well proven, effective, and generally safe treatment for peptic ulcer, it has some disadvantages which make the development of other antisecretory agents worthwhile. This review discusses a number of these newer drugs.

Histamine H2-antagonists: Ranitidine is the first generally available new agent of this group and the most studied; others include oxmetidine, AH 18801, and SKF 93479. Differences in potency of H 2-receptor blockade in comparison with cimetidine mean that lower daily doses can be used but increased ulcer healing rates are unlikely to occur consequentially. Both ranitidine and oxmetidine are as effective as cimetidine for duodenal ulcer and probably other peptic lesions as well. Differences in the pattern of adverse effects will be important; ranitidine and oxmetidine, unlike cimetidine and AH 18801, do not interfere with hepatic microsomal enzyme activity and ranitidine does not share cimetidine’s anti-androgenic activity. Whether histamine H 2-antagonists alter the gastric environment so as to favour significant nitrosamine synthesis remains debatable.

Pirenzapine, a tricyclic derivative, has selective anti-muscarinic actions and inhibits gastric acidity to a similar extent to conventional anticholinergics, but largely without affecting smooth muscle. Some minor atropine-like effects such as dry mouth may be seen with higher doses. It increases the healing rate of duodenal and probably also gastric ulcer, and is useful as an adjunct to histamine H 2-antagonists in the Zollinger-Ellison syndrome.

Prostaglandins: Naturally occurring prostaglandins such as PGE 1 and A 1 have potent gastric antisecretory effects but only when given intravenously. Some synthetic PGE 2 analogues such as 16, 16-dimethyl PGE 2, and 15(S)15-methyl PGE 2 have a longer duration of antisecretory action when taken orally. However, prostaglandins can inhibit experimental ulceration independently of any antisecretory action and appear to have a ‘cytoprotective’ effect on gastric mucosa. Clinical data are fragmentary but healing of duodenal ulcer by PGE 2 at non-antisecretory doses has been demonstrated; in general, the results seemed to favour PGE 2 treatment. Secretory diarrhoea and abdominal cramps are notable unwanted effects which may limit the type and dose of prostaglandins used commercially.

Psychotherapeutic drugs: The tricyclic antidepressant trimipramine, and trithiozine, a tranquilliser, probably increase the healing of peptic ulcers. Other tricyclics and their derivatives might also be equally effective, e.g. doxepin and the antisecretory agent LM 24056.

Dopamine agonists and antagonists: Dopamine agonists have been shown to have antisecretory properties while dopamine antagonists, e.g. metoclopramide and sulpiride, may reduce gastric stasis and bile reflux. Thus, both have been proposed as therapy for peptic ulcer, but clear supporting evidence is not yet available; metoclopramide has Been tested and its effects in gastric ulcer were disappointing.

Opiate receptor agonists and antagonists: Findings with these agents are interesting but confusing. Both morphine and naloxone reduce gastric secretion but naloxone abolishes the reduction of gastric acid output produced by the peripheral opiate agonist loperamide. Perhaps different effects occur at different doses: no application to ulcer treatment has as yet been attempted.

Others: Other drugs of possible value in peptic ulceration include proglumide, omeprazole, fenoctimine, cromones and somatostatin, but need much further study.

Keywords

Peptic Ulcer Cimetidine Duodenal Ulcer Ranitidine Sulpiride 

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Copyright information

© ADIS Press Australasia Pty Ltd 1983

Authors and Affiliations

  • K. W. Somerville
    • 1
  • M. J. S. Langman
    • 1
  1. 1.University Department of TherapeuticsUniversity of Nottingham, City HospitalNottinghamEngland

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