Stilamin Mechanism of Action

Pharmacology: Pharmacodynamics: Stilamin 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 gastro-intestinal tract.
Physiologically, somatostatin is found mainly in the gastrointestinal tract and in the hypothalamus.
Somatostatin inhibits the release of gastrin, gastric acid and pepsin which supports its indication in the treatment of upper G.I., 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 under 175 ng/L.
Following i.v. administration, somatostatin shows a very short plasma half-life which, as measured by radioimmunoassay, lies between 1,1 and 3 minutes in normal subjects, between 1,2 and 4,8 minutes in subjects with liver disease, between 2,6 and 4,9 minutes in subjects with chronic renal failure.
Following an i.v. infusion at a rate of 75 μg/h, the plateau level was obtained within 15 minutes and reached 1250 ng/L. The metabolic clearance rate was around 1L/min. and the half-life around 2,7 min.
After i.v. injection of 2 μg of 125-I-thyrosine somatostatin, urinary excretion contained 40% of the radioactivity after 4 hours and 70% after 24 hours.
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.