Treatment of endocrine and nonendocrine secretory diarrheal states with Sandostatin.
Endocrine tumors of the gastroenteropancreatic (GEP) axis elaborate excessive amounts of peptides that are potent intestinal secretagogues. The actions of these peptides on intestinal transport of water and electrolytes lead to the accumulation of fluid in the intestinal lumen and diarrhea. One of the most clinically relevant secretagogues is vasoactive intestinal polypeptide (VIP). Other relevant secretagogues elaborated from tumors are serotonin, prostaglandins, and kinins. Sandostatin (octreotide, Sandoz, Basle, Switzerland), a long-acting octapeptide analog of somatostatin, inhibits experimentally induced intestinal secretion and has been used successfully to treat patients with secretory diarrhea refractory to other pharmacotherapy. The effective dose is in the range of 50 to 200 micrograms, given subcutaneously two or three times daily. The mechanism for the inhibitory effect on secretion is not clearly understood but it appears to involve inhibition of the adenylate cyclase-cyclic adenosine monophosphate system as well as interference with calcium as an intercellular mediator of enterocyte secretion. A particularly interesting use of this drug has been to treat the watery diarrhea seen in patients with acquired immunodeficiency syndrome. It is also effective in other types of secretory diarrhea not associated with endocrine tumors. These include diabetic diarrhea, idiopathic secretory diarrhea of infancy, and high output ileostomy diarrhea.
Gaginella
T S
TS
Gastrointestinal Diseases Research, G.D. Searle Co, Skokie, IL 60077.
O'Dorisio
T M
TM
Fassler
J E
JE
Mekhjian
H S
HS
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004064:Digestive System / Q000187:drug effects; D005770:Gastrointestinal Neoplasms / Q000150:complications; D006801:Humans; D015282:Octreotide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000150:complications
D015282:Octreotide