Octreotide in the Treatment of Disorders of the Gastrointestinal System

Summary

Octreotide is a long acting synthetic analogue of native somatostatin that exerts a potent inhibitory effect on the release of a wide variety of peptide hormones from the gastroenteropancreatic endocrine system. It represents a new dimension to traditional therapies in the treatment of various conditions characterised by excessive peptide production and secretion, particularly when conventional therapeutic approaches have either been exhausted or have provided suboptimal symptomatic control.

While emergency sclerotherapy remains the definitive treatment for both the arrest of acute variceal bleeding episodes and the prevention of further bleeding, its effective use depends on the patients being admitted to a hospital well versed in the procedure. There remains, therefore, a need for an easily administered and effective treatment for acute variceal bleeding emergencies. Although not all investigators agree, it appears that somatostatin is effective, at least for the duration of its administration. Given its evident advantages over somatostatin, octreotide is likely to make a major contribution towards the treatment of variceal bleeding, at least as an emergency treatment during the bleeding crisis.

The potential for octreotide in the management of gastrointestinal and pancreatic fistulae is considerable. While sharing the inhibitory actions of native somatostatin on gastrointestinal motility and secretion, it can be administered at home by suitably motivated patients.

Suppression of gastrointestinal peptides from the gastrointestinal tract by octreotide appears to parallel symptomatic improvements in patients with dumping syndrome, with normalisation of plasma glucagon and insulin profiles as well as suppression of vasoactive intestinal polypeptide (VIP), motilin, neurotensin, pancreatic polypeptide and C peptide being reported.

Release of polypeptide hormones, such as VIP and gastrin, by tumour cells in the gastroenteropancreatic system results in profuse diarrhoea. While the nature of the diarrhoea depends on the specific peptide secreted by the tumour, all possess a common secretory mechanism which makes them sensitive to treatment with octreotide.

Octreotide is suitable for the treatment of VIPoma since it inhibits released VIP. Although the available data are derived primarily from small studies and case reports, initial responses are encouraging. By reducing the circulating levels of VIP, octreotide improves diarrhoea in these patients. Octreotide has also been evaluated in several trials in patients with the carcinoid syndrome, with symptomatic improvement being observed in over 75% of cases. Clinically significant improvements in diarrhoea (elimination, or reduction of > 50%) have been observed in the great majority (up to 83%) of treated patients. Slowed tumour growth, as well as an improvement in diarrhoea, has been observed during long term treatment.

A number of miscellaneous conditions can give rise to severe secretory diarrhoea, and include long standing neuropathic diabetes mellitus, short bowel syndrome after intestinal resection, intestinal graft-versus-host disease and coeliac plexus block. Idiopathic hypersecretory diarrhoea may also occur, particularly in infants. A number of studies and patient reports have shown octreotide to be a valuable adjunct in the management of patients with such conditions, and to be worthy of further investigation. Now that case report data have been confirmed by clinical trials, it is becoming evident that octreotide is a valuable treatment in the management of otherwise treatment-refractory severe diarrhoea in AIDS patients.