Hypersensitivity to racecadotril: a case report.
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Antidiarrheals↗
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High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients.
Thirty-seven colorectal cancer patients with grade 1-4 diarrhea (NCICTC) caused by chemotherapy with 5-FU-containing regimens, received oral loperamide at the initial dose of 4 mg followed by 4 mg every 8 h (total dose 16 mg/24 h). Twenty-five patients (69%) were diarrhea-free and were considered to be treatment responders. Eight-four percent of the patients with grade 1 or 2 diarrhea achieved a response, but only 52% of those with grade 3-4 diarrhea. These data seem to suggest that high-dose loperamide is effective in patients with moderate diarrhea and can be regarded as the treatment of choice. The patients with more severe diarrhea did not respond so well, and should, perhaps, be given first-line treatment with more effective drugs, such as somatostatin analogues (e.g., octreotide).
Administration, Oral↗
The effects of loperamide on continence problems and anorectal function in obese subjects taking orlistat.
UNLABELLED: Continence problems during treatment with orlistat (a lipase inhibitor) are caused when susceptible patients are exposed to increased volumes of loose, fatty stool. AIM: To investigate the dose-response effects of loperamide on continence and anorectal function in subjects susceptible to continence problems on orlistat. METHOD: Ten obese subjects enterred a randomized controlled, double-blind study of loperamide at placebo, 2, 4, and 6 mg/day in a factorial design. Continence problems during orlistat treatment were self-assessed by patient diary. Anorectal function and continence were assessed by barostat, manometry, and retention testing. RESULTS: Loperamide increased stool consistency with dose (p = 0.07) and this effect reduced continence problems during orlistat treatment (p < 0.05). A bell-shaped dose-response relationship was present with anal sphincter function (p < 0.01) and anorectal sensitivity (p < 0.01). CONCLUSION: Loperamide has beneficial effects on stool consistency and continence in obese subjects taking orlistat. The effect on stool consistency appeared more important than effects on anorectal function.
Adult↗
Saccharomyces boulardii inhibits water and electrolytes changes induced by castor oil in the rat colon.
The biotherapeutic agent Saccharomyces boulardii has been shown to inhibit castor oil-induced diarrhoea in rats. The present study investigated the mechanism(s) of this antidiarrhoeal effect in terms of water and electrolyte (sodium, potassium and chloride) changes using two rat models. A single oral dose of S. boulardii of up to 12 x 10(10) CFU/kg of viable cells did not inhibit castor oil-induced fluid secretion in the enteropooling model. However, the yeast dose dependently reduced castor oil induced fluid secretion into the colon, with a significant protection at 12 x 10(10) CFU/kg. In this model, castor oil reversed net sodium and chloride absorption into net secretion, and increased net potassium secretion into the lumen. Single pre-treatment with S. boulardii at 4 and 12 x 10(10) CFU/kg dose dependently decreased these electrolyte changes. In conclusion, S. boulardii possesses potent anti-secretory properties versus water and electrolyte secretion induced by castor oil in the rat colon.
Animals↗
Diagnosis and treatment of irritable bowel syndrome: state of the art.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a wide variety of presentations that may include abdominal pain, bloating, diarrhea, constipation, or alternating bowel habits. Symptom-based criteria and a limited medical evaluation are used for diagnosis. The heterogeneity of IBS presenting symptoms, together with the pathophysiology of the disorder, is unclear, making treatment challenging. Treatment strategies are focused on specific symptoms, potential underlying disorders in stress responsiveness, and predisposing psychological features. Although only two medications, tegaserod for constipation-predominant IBS and alosetron for diarrhea-predominant IBS, are specifically indicated, a wide variety of treatment options are available and are discussed in this review.
Anti-Bacterial Agents↗
A new look at irritable bowel syndrome [IBS]: a neuroenteric disorder.
Irritable bowel syndrome is difficult to treat because of poorly defined pathophysiology, lack of diagnostic marker, and until recently, limited pharmacotherapy. After diagnosis, treatment includes diet and behavior modifications, along with pharmacologic treatment for mild disease and severe cases.
Antidepressive Agents↗
Acute diarrhea in developed countries. A rationale for self-treatment.
Acute diarrhea is a common, nonlethal condition that causes frequent inconvenience and economic loss. People rarely consult physicians for this problem. Epidemiologic studies among adults, hospitalized adults, children attending day care centers, homosexual men, and travelers indicate a wide spectrum of etiologic agents. The clinical presentation of acute diarrhea may lead clinicians to consider certain causative agents, but it is not diagnostic of any specific cause. Clinical laboratory studies can detect or isolate pathogens in only a minority of cases. By the time this information is available, patients have usually recovered. For these reasons, early self-treatment aimed at reducing symptoms of acute diarrhea is recommended.
Antidiarrheals↗
Family practitioner's guide to patient self-treatment of acute diarrhea.
The majority of cases of acute, nonspecific diarrhea are of short duration, can be treated symptomatically with nonprescription medications and adequate hydration, and do not require a visit to the physician's office. If the family practitioner can determine via telephone that the patient, or the caller's child, is not experiencing certain signs and symptoms often associated with diarrheal illness that may indicate a more severe condition (e.g., high fever, vomiting, persistent diarrhea, or diarrhea accompanied by blood or severe abdominal or rectal pain), self-treatment may be allowed without an office visit. In addition, if the physician determines that the patient is not suffering from diarrheal dehydration, indicated by dry mouth, excessive thirst (or for children, inadequate fluid intake), wrinkled skin, little or no urination, dizziness, or lightheadedness, the physician may also allow the patient to be treated without an office visit. If, however, the patient is experiencing any of these symptoms, an office visit is required to facilitate further evaluation by the physician.
Acute Disease↗
Oral rehydration in acute infantile diarrhea.
The significance of acute diarrheal illness, a common disorder in infants and children, is presented. Although in developed countries this disease is seldom fatal, it is the second most common reason that children are hospitalized. Methods for managing acute diarrhea and its subsequent dehydration, including intravenous rehydration and refeeding, are discussed, with emphasis placed on the use of oral rehydration solutions.
Acute Disease↗
Acute diarrhea associated with travel.
Travelers' diarrhea, an acute illness that affects between 20 and 50 percent of travelers to high-risk areas, is usually acquired by eating contaminated food, drinking contaminated water, or coming in contact with the contaminated hands of an infected person. Travelers' diarrhea can be caused by bacterial, viral, and parasitic agents. The Travelers' Diarrhea Consensus Conference has recommended prophylactic measures, which include proper preparation of food and beverages, nonantimicrobial agents, and antimicrobial agents. The newer quinolone antibiotics and bismuth subsalicylate may also be useful prophylactically. Appropriate treatment methods include oral fluids and electrolyte replacement, nonspecific agents such as bismuth subsalicylate, antimotility agents such as loperamide hydrochloride and diphenoxylate hydrochloride, and antimicrobial and antiparasitic agents.
Acute Disease↗
Midtrimester abortion induced by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha.
Midtrimester abortion was successfully induced in 35 patients by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha. The dose schedule in this series was an initial injection of 250 mug of 15-ME-PGF2alpha followed by another 250 mug in 2 hours, then 500 mug every 2 hours up to 24 hours; in patients who did not abort within 24 hours the dose was raised to 750 mug every 2 hours until abortion. The mean abortion time was 15.98 hours in this series and 86 per cent of the patients aborted in under 24 hours. Parous patients aborted faster (mean 14.81 hours) than nulliparous patients (mean 17.02 hours) and patients with lower gestational age, 13 to 16 weeks, aborted more quickly (mean 13.98 hours) than patients with gestational age 17 to 20 weeks (mean 16.35). These differences in this series, however, were not statistically significant. Gastrointestinal side effects occurred in 32 of the 35 patients and eight patients had a temperature elevation of more than 1 degree F. during the treatment period. The mean estimated blood loss was 137 plus or minus 42 ml. Thirty patients passed the fetal-placental unit intact, the placenta was removed by sponge forceps in three patients, and by surgical intervention in two patients. There were no failures of technique in this study and none of the patients developed endometritis.
Abortifacient Agents↗
Effects of E prostaglandins, diphenoxylate and morphine on intestinal motility in vivo.
The mechanism of the gastrointestinal motility effects of diphenoxylate and morphine in preventing E prostaglandin (PG) diarrhea was investigated. Duodenal motility studies were conducted in the anesthetized dog. Two contractile force transducers were oriented to record contractions from both the circular and longitudinal muscles. In some experiments the basic electrical rhythm (BER) was also recorded. Blood pressure was monitored from the femoral artery and drug injections were made in the femoral vein. Diphenoxylate shared with morphine the capacity to stimulate circular muscle contractions which correlated with the appearance of spike potentials on the BER. Prostaglandin E1 methyl ester (PGE1ME) showed marked relaxation of the circular muscle and abolishment of spike potentials. PGE1ME also blocked the stimulatory effects of diphenoxylate and morphine on the circular muscle. PGE1ME and PGE2 were found to be equally potent in producing diarrhea in mice. Diphenoxylate and morphine were found to be equally potent in inhibiting PG's diarrhea. These studies suggest that the constipating actions of diphenoxylate and morphine are a consequence of the increased circular muscle activity of the intestine.
Animals↗
Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs.
A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For 10 drugs tested for anti-diarrheal potency significant correlation was observed with binding to brain opiate receptors when binding was carried out in sodium-containing medium. These data add support to the hypothesis that stereospecific opiate binding sites are pharmacological receptors which mediate analgesia and anti-diarrheal action. We found that neuroleptics can bind to opiate receptors with affinities in the micromolar range, in agreement with reports by others. The anti-diarrheal compound loperamide exhibits no significant central opiate effects but binds to opiate receptors from brain in vitro with high affinity. Evidency is presented suggesting that the lack of specific analgesic effect is the result of poor penetration through the blood--brain barrier. Our results lend further support to the similarity of opiate receptors in the brain and in the intestinal tract.
Analgesics, Opioid↗
Relationship between anti-diarrheal activity and binding to calmodulin.
Several neuroleptics known to bind to calmodulin were tested for anti-diarrheal activity and were compared with the opiate anti-diarrheals loperamide and diphenoxylate. All inhibited the intestinal fluid secretion induced by 16,16-dimethyl prostaglandin E2 and castor oil-induced diarrhea in rats as a function of dose, the order of potency being loperamide approximately equal to diphenoxylate greater than chlorpromazine greater than promethazine greater than amitriptyline. The opiates loperamide and diphenoxylate were found to compete with [3H]trifluoperazine binding to calmodulin in the presence of calcium. These opiates were approximately 3 times more potent inhibitors of [3H]trifluoperazine binding than chlorpromazine. A positive correlation between calmodulin binding and anti-diarrheal activity was demonstrated.
16,16-Dimethylprostaglandin E2↗
Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analogue SMS 201-995.
The somatostatin analogue SMS 201-995 has been reported to be effective in treating adult secretory diarrhea due to vasoactive intestinal polypeptidoma. We report the effectiveness of this drug in treating severe refractory secretory diarrhea of uncertain etiology in an infant. The patient developed diarrhea within the first few days of life, with mean stool output of 250 ml/kg.day (expected 10 ml/kg.day). Small bowel biopsy showed mild focal enteritis. Serum levels of known gastrointestinal secretagogues were normal. No tumor was detected. Diarrhea was not adequately controlled by various drug treatments. Addition of subcutaneous SMS 201-995 produced a significant sustained decrease in stool output to 80-100 ml/kg.day. During SMS 201-995 treatment, no metabolic, hormonal, or growth abnormalities were noted. SMS 201-995 was discontinued after 9 mo because of patient irritability. Stool output rose immediately to 173 ml/kg.day, and remained stable for 6 mo. It is concluded that SMS 201-995 was a safe and effective treatment in this single childhood case of severe idiopathic secretory diarrhea.
Antidiarrheals↗
Clinical trial of clonidine hydrochloride as an antisecretory agent in cholera.
Clonidine hydrochloride (an alpha 2-adrenoceptor agonist) was tested for antisecretory effects in patients with cholera in a randomized controlled trial. Nineteen adults with diarrhea due to Vibrio cholerae were treated with clonidine (0.9 mg/24 h orally for 72 h) and 18 served as controls. During the first 24 h of treatment and for 24 h afterwards, the mean +/- SD concentrations of sodium (in millimoles per liter) in the stools of clonidine-treated patients were 120.6 +/- 10.9 and 112.3 +/- 11.9, which were significantly lower than 135.5 +/- 17.1 and 125.0 +/- 16.4 in the controls (p less than 0.01). Stool chloride concentrations (in millimoles per liter) were also significantly less in the clonidine group during the same periods: 82.1 +/- 16.8 and 62.4 +/- 19.4 vs. 92.1 +/- 18.3 and 78.0 +/- 23.0, respectively (p less than 0.05). Concentrations of potassium but not bicarbonate were also significantly reduced in the stools of clonidine-treated patients (p less than 0.05). However, there were no significant differences in the mean +/- SD stool volumes (in liters) between the clonidine and the control group in any of the six 12-h periods after treatment or in the cumulative volumes in 72 h (24.2 +/- 10.6 and 22.9 +/- 8.3, respectively). We conclude that clonidine causes modest reduction of stool electrolyte loss but does not significantly reduce fecal fluid loss in patients with cholera.
Adult↗
Effect of psyllium, calcium polycarbophil, and wheat bran on secretory diarrhea induced by phenolphthalein.
BACKGROUND: Fiber and water-holding agents are used for the treatment of constipation. In what may appear to be a paradox, they are sometimes also used for the treatment of diarrhea; it has been proposed that they sequester water from liquid stools and/or increase the ratio of fecal solids to fecal water and thereby improve stool consistency. The purpose of the present study was to test the validity of this hypothesis in normal subjects in whom secretory diarrhea was induced by phenolphthalein. METHODS: In random sequence, 9 subjects with phenolphthalein-induced diarrhea were treated with placebo, psyllium, calcium polycarbophil, or wheat bran. RESULTS: Calcium polycarbophil and wheat bran had no effect on fecal consistency or on fecal viscosity. By contrast, psyllium made stools firmer and increased fecal viscosity. In a dose-response study in 6 subjects, doses of 9, 18, and 30 g of psyllium per day caused a near linear increase in fecal viscosity. CONCLUSION: Psyllium, but not calcium polycarbophil or wheat bran, improves fecal consistency and viscosity in subjects with experimentally-induced secretory diarrhea.
Acrylic Resins↗
Zaldaride maleate, an intestinal calmodulin inhibitor, in the therapy of travelers' diarrhea.
BACKGROUND: The therapeutic value of zaldaride maleate (Zm), an intestinal calmodulin inhibitor, was examined in patients with travelers' diarrhea, known to be caused by enterotoxigenic Escherichia coli (ETEC) and other bacterial agents. METHODS: One hundred seventy-six American students acquiring diarrhea in Mexico during the summer of 1991 were given Zm in doses of 5 mg, 10 mg, or 20 mg, or a matching placebo, four times a day for 48 hours. RESULTS: The duration of diarrhea was reduced by 53% in the group given the 20-mg Zm dose (overall P < 0.01). Curative antibiotics were required post-treatment only in the placebo and 5-mg Zm groups (P < 0.01). The number of unformed stools passed during 0-48 hours of therapy with the highest Zm dose was reduced compared with placebo by 36% for all subjects (P < 0.05), by 39% for ETEC diarrhea (NS), by 45% for those with any bacterial agents (NS), and by 38% for those without an identifiable bacterial agent (NS). CONCLUSIONS: The fact that a calmodulin inhibitor decreases the severity and duration of travelers' diarrhea has therapeutic implications and suggests that calmodulin and intracellular calcium may serve as mediators of diarrhea in bacterial enteric infection.
Adolescent↗