Somatostatin in acute bleeding oesophageal varices. Pharmacology and rationale for use.
Somatostatin was originally isolated from the hypothalamus, but has subsequently been found throughout the whole gastrointestinal tract. It exerts an inhibitory effect upon numerous functions of the body, and, therefore, increasing attention has been focused on its potential as a therapeutic agent with cytoprotective properties and a potent inhibitory action on a wide variety of functions in endocrine diseases, cancer and gastrointestinal haemorrhage, including bleeding from oesophageal varices. As somatostatin has a very short plasma half-life and requires administration by continuous infusion to maintain therapeutic levels, stable long-acting analogues have been developed. The analogue octreotide has been shown to have a plasma half-life of 113 minutes and to produce a profound selective inhibition of growth hormone. Hepatic excretion of octreotide has been estimated to be between 30 and 40% in healthy volunteers; no data are available in cirrhotic patients. A review of published data assessing systemic and hepatic haemodynamics in animals and humans over varying dosage regimens of somatostatin and octreotide reveals that cardiac output, arterial pressure and peripheral resistance are modified more in animals than in humans. Hepatic haemodynamics are significantly altered in animals as well as in humans in most of the studies. Circumstantial evidence is provided indicating that the mechanisms of action of somatostatin and octreotide in the therapy of bleeding oesophageal varices are mainly mediated by a splanchnic vasoconstrictive effect. Furthermore, gastric acid suppression and potential enhancement of platelet aggregation may contribute to the beneficial outcome after treatment of oesophageal varices with somatostatin.
Hanisch
E
E
Department of Surgery, University Hospital Frankfurt/Main, Federal Republic of Germany.
Doertenbach
J
J
Usadel
K H
KH
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D004932:Esophageal and Gastric Varices / Q000188:drug therapy*; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D015282:Octreotide / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D013004:Somatostatin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D013004:Somatostatin; D015282:Octreotide