Pharmacodynamic effects of Sandostatin in the gastrointestinal tract.

Somatostatin is widely distributed throughout the human gastrointestinal system. There it is found in neurons and fibers of both the submucosal and the myenteric plexus and the pancreas as well as in the D cells of the stomach, gut and pancreatic islets. Whereas in the intestinal nervous system, in the duodenum and the pancreas, somatostatin-14 appears to be the predominant molecular form, the endocrine-type D cells of the intestine primarily contain somatostatin-28. Somatostatin peptides may act very differently at different sites, as hormones, as paracrine substances or neurotransmitters. Because of this complexity of action, very little is known about the physiological effects of somatostatin in the gastrointestinal tract. In contrast, the pharmacological actions of natural synthetic somatostatin have been thoroughly studied and have given rise to many therapeutic applications. Octreotide, an analogue with a longer half-life and higher potency, has greatly facilitated the clinical application of somatostatin. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions. The somatostatin analogue exerts a long-lasting inhibitory action on gastric acid, pancreatic enzyme and bicarbonate secretion as well as on bile flow. It is also able to inhibit stimulated intestinal secretion, the release of neuropeptides from the gut and the pancreas. It can also prolong orocecum transit time and prevent gallbladder contraction. It inhibits absorption of nutrients and exerts inhibitory effects on splanchnic hemodynamics. It is because of these actions that somatostatin has attracted so much attention in the treatment of different gastrointestinal disorders.

Pharmacodynamic effects of Sandostatin in the gastrointestinal tract.

Somatostatin (SST) is widely distributed throughout the human gastrointestinal system. There, it is found in neurons and fibers of both the submucosal and myenteric plexus and the pancreas, and also in the D cells of the stomach, gut, and pancreatic islets. Whereas in the intestinal nervous system, duodenum, and pancreas, somatostatin-14 (SST-14) appears to be the predominant molecular form, the endocrine-type D cells of the intestine primarily contain somatostatin-28 (SST-28). SST peptides may act very differently at different sites, as hormones, paracrine substances, or neurotransmitters. Because of this complexity of action, very little is known about the physiological effects of SST in the gastrointestinal tract. In contrast, the pharmacological actions of natural synthetic SST have been thoroughly studied and have given rise to many therapeutic applications. Octreotide, an analogue with a longer half-life and higher potency, has greatly facilitated the clinical application of SST. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions. The SST analogue exerts a long-lasting inhibitory action on gastric acid, pancreatic enzyme, bicarbonate secretion, and on bile flow. It also inhibits stimulated intestinal secretion, ie, the release of neuropeptides from the gut and pancreas. It can also prolong orocecum transit time and prevent gallbladder contraction. It inhibits absorption of nutrients and exerts inhibitory effects on splanchnic hemodynamics. It is because of these actions that SST has attracted so much attention in the treatment of different gastrointestinal disorders.

Reduction in early recurrence of variceal bleeding by propranolol.

Survival after variceal bleeding depends greatly on the outcome of the immediate posthaemorrhagic period. This may in turn depend on the recurrence of bleeding. We therefore prospectively evaluated the influence of propranolol on the recurrence of variceal haemorrhage during the early period after the acute bleeding episode. Twenty consecutive patients with acute variceal haemorrhage and liver disease were randomly assigned to treatment either with propranolol or placebo orally for 14 days. Propranolol significantly decreased the rate of recurrence of variceal haemorrhage during this early period (p = 0.0028; 95% confidence interval in the placebo group, 90 +/- 20%; in the beta blocker group, 20 +/- 26%). Whereas a recurrence of variceal bleeding occurred in 9 of 10 patients in the placebo group, only 2 of 10 rebled during treatment with propranolol. These results suggest that propranolol may prevent rebleeding in the crucial early period after acute haemorrhage from oesophageal varices.

Human pharmacological effects of SMS 201-995 on gastric secretion.

The inhibition of pentagastrin-stimulated-(3 micrograms kg-1 h-1) gastric acid secretion by various doses of intravenous and subcutaneous SMS 201-995, a somatostatin analogue, was investigated in healthy volunteers by means of gastric aspiration, using phenol red as a volume marker. The intravenous doses were compared with the standard dose of somatostatin-14, 3.5 micrograms kg-1 h-1. Similarly, SMS 201-995-induced inhibition of gastric acid secretion was compared with that of exocrine pancreatic secretion assessed by gastroduodenal aspiration. The results can be summarized as follows: SMS 201-995 is a potent inhibitor of gastric acid secretion, exerting near maximal inhibition at a dose of greater than or equal to 0.56 micrograms kg-1 h-1. Near maximal inhibition equals that achieved with SST-14 (3.5 micrograms kg-1 h-1). Pancreatic enzyme secretion appears to be strongly inhibited by lower doses of SMS 201-995 than gastric secretion. Single subcutaneous injections of SMS 201-995 produce an inhibition of gastric acid secretion lasting for many hours. Near maximal inhibition was obtained with a dose of 100 micrograms.

A double-blind randomized, controlled study to investigate the efficacy of cimetidine given in addition to conventional therapy in the prevention of stress ulceration and haemorrhage in patients with acute spinal injury.

The efficacy of cimetidine, 1.2 and 2.4 g/day, compared to placebo treatment given in addition to conventional therapy, which included antacids, in the prevention of gastroduodenal lesions associated with stress in 105 patients with acute spinal injury was investigated. Haematemesis was only observed in 1 placebo-treated patient. Of the 84 patients who completed the 10-day treatment and underwent endoscopy, 12 out of 43 cimetidine-treated patients and 11 out of 41 patients who received placebo were found to have gastroduodenal ulceration and/or erosions. Mean circulating concentrations of gastrin, pancreatic polypeptide and secretin were similar in all groups of patients. Whilst cimetidine has been shown to reduce the incidence of ulceration in patients suffering cranial and thermal injuries, the present study failed to demonstrate a prophylactic effect of cimetidine in the primary prevention of ulcers or erosions in patients with acute spinal injury exceeding that of conventional antacid therapy.