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)

Acetorphan is an orally active inhibitor of enkephalinase (EC 3.4.24.11) with antidiarrhoeal activity in rodents apparently through protection of endogenous enkephalins and a purely antisecretory mechanism. Its antidiarrhoeal activity in man was assessed in an experimental model of cathartic induced secretory diarrhoea as well as in acute diarrhoea of presumed infectious origin. In six healthy volunteers receiving castor oil and pretreated with acetorphan or placebo in a crossover controlled trial, the drug significantly decreased the number and weight of stools passed during 24 hours. About 200 outpatients with severe acute diarrhoea (more than five stools per day) were included in a randomised double blind study of acetorphan against placebo. The significant antidiarrhoeal activity of acetorphan was established using a variety of criteria: (i) the duration of both diarrhoea and treatment were diminished; (ii) no acetorphan treated patient withdrew from the study whereas five dropped out because of worsening in the placebo group; (iii) the frequency of symptoms associated with diarrhoea--for example, abdominal pain or distension, nausea and anorexia--remaining after two weeks was nearly halved; (iv) using visual analogue scales acetorphan treatment was found more effective than placebo by both investigators and patients. There was statistically no significant difference between acetorphan and placebo in respect of side effects, particularly constipation, which often accompanies the antidiarrhoeal activity of mu opioid receptor agonists this difference is attributable to the lack of antipropulsive activity of acetorphan in man. The efficacy and tolerance of acetorphan suggest that enkephalinase inhibition may represent a novel therapeutic approach for the symptomatic management of acute secretory diarrhoea without impairing intestinal transit.
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PMID:Effects of acetorphan, an enkephalinase inhibitor, on experimental and acute diarrhoea. 847 99

In order to assess and characterize adynamic ileus (AI) complicating acute diarrhoea (AD) in infants, 802 consecutive admissions were studied. Diagnosis was suspected in 23 patients with abdominal distension and confirmed by radiological study in 16 whose age range was 14 ds to 6 mo. Of these late patients, 9/16 were malnourished. Age was less than, but nutritional status similar to that of all patients admitted with ADD. Vomiting (14/16), silent or almost silent abdomen (10/16), protracted course of diarrhoea (9/16) and increased gastric content (6/16) were the most common clinical findings in addition to abdominal distension and X Ray films suggestive of AI (inclusion criteria). Lack of constipation was a relevant finding. Treatment included temporal discontinuance of oral feedings, intravenous fluids administration, nasogastric and rectal tube and antibiotics. Lethality rate was 4/16. Duration of AI was an average of 2 days in survivors and 4 days in the remainder infants. It is concluded that AI is an infrequent complication of AD (0.19% of cases), which should be suspected in infants less that 6 mo old with diarrhoea and abdominal distension.
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PMID:[Manifestations of paralytic ileus in infants hospitalized for acute diarrheal syndrome]. 215 17

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

To establish the short-term and long-term results of current treatment of irritable bowel syndrome (IBS), 104 patients were studied prospectively. All patients were treated similarly and the results were assessed after a few weeks and then after at least 5 years. IBS can be diagnosed more easily than has been suggested--72% of this series were correctly diagnosed by their referring doctor, and only 12% required radiological studies to exclude organic disease. The response to treatment was considerably better than expected, possibly because of the more aggressive use of high-fibre diets and bulking agents. Thus, 85% of patients were rendered virtually symptom-free in the short term, and 68% were still virtually symptom-free 5 years later. The response to treatment was better in men than in women, in those with constipation than with diarrhoea, when the symptoms had initially been triggered by an episode of acute diarrhoea, and in patients with a relatively short history. With a few simple investigations, sympathetic explanation, and appropriate treatment, most patients with IBS have a good prognosis.
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PMID:Prognosis in the irritable bowel syndrome: a 5-year prospective study. 288 51

The use of antimicrobial agents for the treatment of acute diarrhoea has become more common with the introduction of quinolone compounds, which are active against most types of bacterial pathogens. Despite the fact that such drugs have been used for empirical therapy or even for prophylaxis, current opinion would restrict their use to specific groups of patients who are likely to show particular benefit from them. Non-specific therapy seems a more appropriate initial treatment for cases of acute, non-dysenteric diarrhoea. Clinical trial data are presented here comparing the effects of loperamide oxide 1 and 2 mg to those of placebo and loperamide 2 mg in this condition. All the drug preparations were significantly superior to placebo, in particular reducing the time to complete relief of symptoms to about 24 hours, as opposed to 45 hours on placebo treatment. Of these preparations, loperamide oxide 1 mg is to be preferred, as it produces fewer constipation-like episodes after treatment. The introduction of loperamide oxide 1 mg represents a useful advance in the non-specific treatment of acute, non-dysenteric diarrhoea.
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PMID:First-line treatment in acute non-dysenteric diarrhoea: clinical comparison of loperamide oxide, loperamide and placebo. UK Janssen Research Group of General Practitioners. 754 57

We evaluated two doses of loperamide oxide (1 mg and 2 mg) and placebo in the treatment of acute diarrhea in 230 adult patients. Two tablets were taken initially and then one tablet after each watery, loose, or pasty stool to a maximum of eight tablets per day. The median time to complete relief was 27 hours 55 minutes for the 1-mg loperamide oxide group, 25 hours for the 2-mg loperamide oxide group, and 40 hours 35 minutes for the placebo group (P < 0.05). The investigator rated treatment as good or excellent for 78% of patients in each group treated with loperamide oxide and 62% of patients who received placebo. Constipation-like periods were no more common with loperamide oxide than with placebo. Adverse events were reported by four patients given loperamide oxide and three patients given placebo. The results demonstrate superior efficacy of loperamide oxide compared with placebo in the treatment of acute diarrhea in adults; because both doses of loperamide oxide are equally effective, the lower (1-mg) dose is preferred.
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PMID:Loperamide oxide in the treatment of acute diarrhea in adults. 769 94

The antidiarrhoeal properties of acetorphan, an inhibitor of enkephalinase (EC 3.4.24.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs--that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan.
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PMID:The enkephalinase inhibitor, acetorphan, in acute diarrhoea. A double-blind, controlled clinical trial versus loperamide. 848 68

Racecadotril is an oral enkephalinase inhibitor used in the treatment of acute diarrhoea. It prevents the degradation of endogenous opioids (enkephalins), thereby reducing hypersecretion of water and electrolytes into the intestinal lumen. In a randomised double-blind study in 6 adult volunteers with castor oil-induced diarrhoea, racecadotril significantly reduced stool weight and stool number in comparison with placebo. Similar results have been obtained in treating castor oil-induced diarrhoea in rats. Racecadotril was significantly more effective than placebo in randomised double-blind studies in adults or children with diarrhoea (of infectious origin or in adults with HIV infection). In well controlled trials, racecadotril had efficacy similar to that of loperamide and was generally as effective as loperamide-oxide. Racecadotril had a similar tolerability profile to placebo, and was better tolerated than loperamide, in adults and children with diarrhoea. It caused significantly less constipation after resolution of diarrhoea than loperamide.
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PMID:Racecadotril. 1080 38

Dientamoeba fragilis is a parasite that has been recognized as a causative agent of gastrointestinal symptoms. The search for genetic variation in D. fragilis based on the small-subunit (SSU) rRNA gene using restriction fragment length polymorphism was found not useful for molecular epidemiology. In this study, genetic variability of different clinical isolates of D. fragilis was explored by high-resolution melting curve (HRM) following polymerase chain reaction (PCR) in a one-step closed-tube method. Thirty fecal samples from irritable bowel syndrome (IBS) patients having D. fragilis trophozoites and negative for other organisms were involved in this study. According to the type of diarrhea, eight patients had acute, 14 patients had chronic intermittent, and eight patients had diarrhea alternating with constipation. HRM proved that four profiles (subtypes) were present as detecting by scanning mutation. One of these profiles (profile 1) was predominant (50%). Profile 2 was present on 20%. Profiles 3 and 4 were present on 16.7% and 13.4%, respectively. No mixed profiles were detected among the samples. The melting curves characterized by T(m)1=77.17+/-0.29 degrees C in profile 1, T(m)1=77.37+/-1.45 degrees C in profile 2, T(m)1=74.24+/-0.08 degrees C and T(m)2=79.64+/-0.09 degrees C in profile 3, and T(m)1=75.51 +/- 0.09 degrees C and T(m)=79.42 +/- 0.09 degrees C in profile 4. The relation between these profiles and types of diarrhea proved that the majority of patients having profile 1 (73.4%) and profile 4 (75%) had chronic intermittent diarrhea. All of the patients having profile 2 had acute diarrhea while all of the patients having profile 3 had diarrhea alternating with constipation. Although profile 1 was detected among all types of diarrhea, it was corresponding to 11/14 of patients with chronic intermittent diarrhea. All the differences were clinically and statistically significant. In conclusion, HRM following PCR was proved as a wide variation on D. fragilis genotypes that could be related to the characters of diarrhea among IBS patients. As the differences in HRM reflect different sequences of SSU RNA gene, thus, another study for identifying the sequences of these isolates (profiles) will be done and published later.
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PMID:Genetic diversity of Dientamoeba fragilis isolates of irritable bowel syndrome patients by high-resolution melting-curve (HRM) analysis. 1954 48

Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.
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PMID:A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril. 2266 49


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