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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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 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.[1]


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