Somaset Mechanism of Action

Pharmacology: Mechanism of Action: Somatostatin is a 14-amino acid oligopeptide that was originally isolated from the hypothalamus of animals and, later, found in both epithelial cells and nerve fibers throughout the whole of the digestive system. Somatostatin is thought to act mainly as a local transport substance, thus having a role in both the regulation of endocrine and exocrine secretions and of gastrointestinal motility. When administered at pharmacological doses, somatostatin will inhibit gastrointestinal function and motility, as well as resorption within the digestive tract.
Pharmacodynamics: Somatostatin is a synthetic cyclic 14 amino-acid peptide, which is identical in structure and action to natural somatostatin.
By I.V. infusion in humans, somatostatin causes inhibition of growth hormone, thyroid stimulating hormone, insulin, and glucagon secretion as well as inhibition of gastric acid secretion. It also affects the absorption, motility, splanchnic blood flow, and trophic functions of the gastrointestinal tract (GIT).
Physiologically, somatostatin is found mainly in the GIT and in the hypothalamus. Somatostatin inhibits the release of gastrin, gastric acid, and pepsin, which supports its indication in the treatment of upper gastrointestinal haemorrhage. Furthermore, somatostatin is capable of reducing remarkably splanchnic blood flow without causing significant variations in the systemic arterial pressure, which proves to be valuable for the management of oesophageal variceal haemorrhage. Somatostatin reduces both pancreatic endocrine and exocrine secretion, which makes it effective in the prophylaxis and treatment of postoperative complications of pancreatic surgery.
The positive effect of somatostatin in the management of diabetic ketoacidosis can be ascribed to its suppression activity of glucagon secretion.
Pharmacokinetics: In healthy persons, the plasma level of endogenous somatostatin is low, generally well <175 ng/L.
Following I.V. administration, somatostatin shows a very short plasma half-life (t_1/2), which, as measured by radioimmunoassay, lies between 1.1 and 3 min in normal subjects, between 1.2 and 4.8 min in subjects with liver disease, between 2.6 and 4.9 min in subjects with chronic renal failure.
Following an I.V. infusion at a rate of 75 mcg/hr, the plateau level was obtained within 15 min and reached 1250 ng/L. The metabolic clearance rate was around 1 L/min and the t_1/2 was around 2.7 min.
After I.V. injection of 2 mcg of 125 L-thyrosine somatostatin urinary excretion contained 40% of the radioactivity after 4 hrs and 70% after 24 hrs.
Somatostatin is rapidly metabolized in the liver through the action of endopeptidases and aminopeptidases, resulting in cleavage between the N-terminus and the cyclized portion of the molecule.