Somatostatin, a naturally occurring
peptide, displays a wide range of
biological actions, mainly inhibitory ones, that can make it an appropriate
drug for the treatment of a variety of digestive diseases. The marked effect of the
peptide on splanchnic hemodynamics together with its inhibitory action on
acid-peptic and pancreatic exocrine secretions represent the rationale for the use in upper gastrointestinal (GI)
bleeding and surgical conditions of the pancreas. Besides the hemodynamic effects, other pharmacological actions of
somatostatin may contribute to its therapeutic efficacy in active variceal
bleeding. The
peptide indeed increases lower esophageal sphincter pressure (LESP), thereby reducing the inflow of blood into the submucous venous plexus of the esophagus and hence into the
esophageal varices. Through its inhibitory action on
acid-peptic secretion,
somatostatin may also inhibit peptic digestion of the clot at the site of hemostasis on the
varix itself. In addition, the natural
peptide was shown to enhance human platelet aggregation in vitro, whose stimulation can activate the
hemostatic process. Since its short half-life makes continuous
intravenous infusion mandatory, several long-acting analogs have been synthesized. Amongst the hundreds of
cyclic peptides synthesised,
octreotide (which binds mainly to
SSTR-2 and SSTR-5 receptor subtypes) has been the most extensively investigated. A thorough analysis of the pharmacological activities and therapeutic efficacy of the native
somatostatin and the synthetic analogs reveals that the
biological actions of these
peptides are not always identical. These differences appear to be related to the different affinities of the natural
hormone and synthetic derivatives for the different receptor subtypes. The fading of the pharmacological effect, which has yet been observed only with analogs, has never been reported with the natural
peptide and may be due to down-regulation of specific receptor subtypes. The safety profile of both natural
somatostatin and synthetic analogs is today well established. Most adverse reactions to these
peptides are merely a consequence of their pharmacological activity and consist mainly of gastrointestinal complaints and effects on
glucose metabolism. They are often of little clinical relevance, especially in the short term. Native
somatostatin and its synthetic analogs are therefore safe and effective drugs for the treatment of a variety of GI disorders. While the native
peptide is the
drug of choice in the acute hospital setting, the synthetic derivatives are better indicated, on outpatient basis, for the long-term management of chronic conditions.