Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0740441 (acute diarrhea)
 2,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Future treatments of functional intestinal disorders (FID) are essentially dependent on the possible pathophysiologic hypotheses. Schematically, symptoms experienced by patients with FID can be attributed to intestinal (small or large intestine) motor disturbances or to visceral sensitivity derangement, which, in turn, may be primary or secondary to an anomalous response to alimentation, liberation of hormones or neuromediators, or to a "stress" situation. New therapeutic agents can be directed against the symptoms experienced by patients (? action on pain or intestinal transit disorders) or against the initial pathophysiologic mechanisms. In the treatment of functional diarrhea, several substances have been proposed recently. Encephalines are peptides with extremely short duration of action which are degraded by two membranous enzymes, encephalinase and carboxypeptidase. Recently, it has been shown that acetorphan, an inhibitor of encephalinase, is efficacious in acute diarrhea. Alpha-2-antagonists are substances which are capable of slowing intestinal transit time and increasing intestinal absorption. Their antidiarrheic action is moderate, and they do not act on abdominal pain. Molecules that do not traverse the neuromeningeal barrier but that act selectively on the digestive tract and are better tolerated are expected. In patients complaining of severe idiopathic constipation substances capable of stimulating colonic motility are useful: substance P or neurotensin analogues might prove interesting. Antagonists of opium receptors such as Naloxone have proved efficacious in the treatment of certain cases of chronic idiopathic intestinal pseudo-obstructions or severe constipation. The development of orally active substances or with hepatic elimination are a prerequisite. Therapy based on well characterized pathophysiologic abnormalities would be welcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapeutic perspectives in the irritable bowel syndrome]. 221 Jan 91

Acute diarrhoea continues to carry a high morbidity and mortality worldwide. Intestinal infection is the major cause of acute diarrhoea although the prevalence of individual pathogens varies according to geographic location. In many countries in the industrialized world, reports of intestinal infections continue to increase; these are largely related to waterborne and foodborne outbreaks. Acute diarrhoea may be due to increased intestinal secretion, commonly as a result of infection with enterotoxin-producing organisms (enterotoxigenic Escherichia coli, Vibrio cholerae) or to decreased intestinal absorption from infection with organisms that damage the intestinal epithelium (enteropathogenic E. coli, Shigella sp., Salmonella sp.). Although oral rehydration therapy has reduced the mortality associated with acute diarrhoea, the diarrhoea attack rate remains unchanged and stool volume often increases during the rehydration process. The search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce stool volume has been going on for more than 20 years. Research during the past decade has highlighted the importance of neurohumoral mechanisms in the pathogenesis of diarrhoea, notably the role of 5-hydroxytryptamine, substance P, vasoactive intestinal polypeptide and neural reflexes within the enteric nervous system. Cholera toxin, E. coli enterotoxins and Clostridium difficile toxin A are known to invoke these mechanisms in diarrhoea pathogenesis. This new dimension of intestinal pathophysiology has already exposed possible novel targets for anti-secretory therapy, namely, 5-HT receptor antagonists, substance P antagonists and the possibility for potentiating the proabsorptive effects of endogenous enkephalins by use of enkephalinase inhibitors. There now seems to be a real possibility that anti-secretory therapy will become more widely available in the future.
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PMID:Novel targets for the pharmacotherapy of diarrhoea: a view for the millennium. 1110 Sep 92

Acute infectious diarrhoea continues to cause high morbidity and mortality worldwide. Although oral rehydration therapy has reduced the mortality associated with acute diarrhoea, stool volume often increases during the rehydration process. Therefore, for > 20 years there has been a search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce stool volume. The most obvious target for antisecretory therapy has been the chloride channel and second messengers within the enterocyte. So far, this search has been largely unrewarding, although recent evidence suggests that a new class of chloride channel blocker is effective in vitro but further evaluation in humans is required. In addition, research during the past decade has highlighted the importance of neurohumoral mechanisms in the pathogenesis of diarrhoea, notably the role of 5-hydroxtryptamine, substance P, vasoactive intestinal polypeptide and neural reflexes within the enteric nervous system. This new dimension of intestinal pathophysiology has already exposed possible novel targets for antisecretory therapy; namely, 5-hydroxytryptamine receptor antagonists, substance P antagonists and sigma-receptor agonists. There is also the possibility for potentiating the proabsorptive effects of endogenous enkephalins by using enkephalinase inhibitors. There now seems to be a real possibility that antisecretory therapy will become more widely available in the future.
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PMID:Novel agents for the control of secretory diarrhoea. 1521 18

Acute diarrhea is a major cause of morbidity and mortality worldwide. Infants and pre-school children are the most vulnerable in whom there are 2-3 million deaths each year as a result of the associated dehydration and acidosis. Although oral rehydration therapy has reduced mortality during the past 30 years ago, the search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce faecal losses in patients with high-volume watery diarrhea has continued for more than 20 years. A variety of potential targets for antisecretory agents have been explored which include loci within the enterocyte (the chloride channel, calcium-calmodulin) and other sites such as enteric nerves and endogenous mediators (such as 5-HT, prostaglandins). Although the potential of calcium-calmodulin inhibition has as yet not been realised, preliminary studies suggest that there are chloride channel blockers under development that will find a place in the management of secretory diarrheas. Recent work has highlighted the importance of neurohumoral mechanisms in the pathogenesis of acute diarrhea. Potentiation of the effects of endogenous enkephalin activity by enkephalinase inhibition has already produced a safe, effective anti-secretory drug, racecadotril. Speculative early work indicates that there may be a role for antagonists of 5-HT, substance P, and VIP receptors. There now seems to be a real possibility that antisecretory therapy will become more widely available in the future.
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PMID:Antisecretory drugs for diarrheal disease. 1669 63