Somatostatin for upper gastrointestinal hemorrhage and pancreatic surgery - A review of its pharmacology and safety

Somatostatin, a naturally occurring peptide, displays a wide range of biolo gical 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 ac tions 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 ve nous plexus of the esophagus and hence into the esophageal varices. Through its inhibitory action on acid-peptic secretion, somatostatin may also inhi bit peptic digestion of the clot at the site of hemostasis on the varix its elf. In addition, the natural peptide was shown to enhance human platelet a ggregation 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 tho rough analysis of the pharmacological activities and therapeutic efficacy o f the native somatostatin and the synthetic analogs reveals that the biolog ical actions of these peptides are not always identical. These differences appear to be related to the different affinities of the natura I hormone a nd 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-re gulation 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 pharmacologic al activity and consist mainly of gastrointestinal complaints and effects o n glucose metabolism. They are often of little clinical relevance, especial ly in the short term. Native somatostatin and its synthetic analogs are the refore safe and effective drugs for the treatment of a variety of Gf disord ers. While the native peptide is the drug of choice in the acute hospital s etting, the synthetic derivatives are better indicated, on outpatient basis , for the long-term management of chronic conditions. Copyright (C) 1999 S. Karger AG, Basel.