Octreotide in the Treatment of Refractory Diarrhea

Abstract

Refractory chronic diarrhea that does not respond to specific antimicrobial therapy or standard unspecific medication may present a challening and serious clinical problem. Octreotide is a candidate drug for the treatment of these patients as it inhibits gastrointestinal motility, pancreatic secretion and inhibits intestinal absorption. Only few mostly uncontrolled studies in small patient groups were published evaluating the efficacy of octreotide in the treatment of patients with chemotherapy-induced diarrhea, short-bowel syndrome, AIDS-associated diarrhea and other conditions with chronic diarrhea not responding to standard treatment. Most of these studies are not conclusive as they yielded either negative or controversial results. Octreotide may be tried in the treatment of refractory diarrhea, in particular AIDS-associated diarrhea if patients do not respond to conventional treatment strategies. Well-designed controlled trials in large patient groups are needed in order to define the place of octreotide in the treatment of patients with refractory diarrhea.

Antisecretory Drugs for Diarrheal Disease

“…The classic enterotoxins, cholera toxin (CT) and Escherichia coli enterotoxins (heat-labile toxin, LT, and heat-stable toxin, ST) activate intestinal secretory 49 pathways in the small intestine without damaging the epithelial cell. The primary site of action of these enterotoxins is the enterocyte through specifi c ligand-receptor interactions.…”

“…With the exception of synthetic opiates, the somatostatin analogue, octreotide and the recent exploitation of endogenous enkephalin activity, none have found their way into the routine treatment of secretory diarrhea. Even octreotide, while clearly effective in the management of diarrhea due to neuroendocrine tumours, has an extremely limited role in other secretory diarrheas [48][49][50] . Although the calmodulin antagonist zalderide maleate had signifi cant anti-secretory activity in experimental models, this was not borne out in clinical trials.…”

“…Octreotide, the somatostatin analogue, has its most important clinical effects on intestinal secretion induced by neuroendocrine tumours, particularly VIPoma, carcinoid tumours and gastrinoma [48,49] . Somatostatin analogues are thought to have their primary action on neuroendocrine tumours by inhibiting release of secretagogues, namely VIP and 5-HT.…”

“…Octreotide has also found a place in the management of high-volume refractory diarrhea in patients with AIDS and in patients with persistent diarrhea following treatment with anti-cancer agents [48,49] . Octreotide (up to 300 g every 8 h) has been compared with standard therapy (high-dose loperamide and diphenoxylate), using stool volume and overall response rate as the primary outcomes.…”

Short small bowel in children. Complications and treatment strategies

“…Octroide, a somatostatin analogue, acts by slowing the intestinal transit, and has an anti-secretory effect but also inhibits intestinal absorption. Octroide can not be administered orally [39,40]. Rectal and colonic administration of medications in SSB patients with severe diarrhoea has an unpredictable effect.…”