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

Intestinal water and electrolyte transport was investigated in vivo and in vitro in rats made tolerant to morphine and subsequently withdrawn with naloxone. Rats were rendered tolerant by injection of a slow-release emulsion containing morphine (75 mg/rat over 48 h), and when challenged with naloxone, they exhibited a characteristic withdrawal syndrome that included acute diarrhea. Morphine tolerance did not influence water absorption from ileal or colonic loops in vivo but naloxone-induced withdrawal provoked a rapid and sustained reduction in absorption. Naloxone did not affect absorption in control animals. In further experiments, sodium and chloride fluxes were measured in isolated stripped ileal mucosa derived from animals made tolerant to morphine and withdrawn with naloxone. Net sodium and chloride absorption was markedly reduced in mucosa derived from withdrawn animals compared with that derived from tolerant animals (Na+: 1.12 +/- 0.76 vs. 5.52 +/- 0.46, and Cl-: 0.60 +/- 0.52 vs. 4.70 +/- 0.80 microEq/cm2 X h, in withdrawn and tolerant animals, respectively; n = 8; p less than 0.001 and p less than 0.005). When an attempt was made to induce withdrawal by adding naloxone in vitro to isolated mucosa derived from tolerant animals, no effect on transport was detected whether the mucosa was stripped of muscle layers or not. Thus naloxone had to be given in vivo to produce withdrawal effects in mucosa studied subsequently in vitro. Naloxone also had an effect in control rats when a 50% reduction in net chloride absorption was observed in isolated ileal mucosa derived from these animals. Net sodium absorption was unaffected. These data support a role for endogenous opiates in the control of intestinal transport and provide a mechanism for the diarrhea associated with opiate withdrawal.
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PMID:Influence of morphine tolerance and withdrawal on intestinal salt and water transport in the rat in vivo and in vitro. 654 Nov 71