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PubMed1984

Effect of intravenous somatostatin on stool output in diarrhea due to Vibrio cholerae.

Somatostatin has been shown to inhibit intestinal secretion induced by a variety of secretagogues. The ability of somatostatin to reduce stool output in patients with cholera was therefore investigated in a double-blind randomized controlled trial. Twenty-two patients with severe purging due to infection with Vibrio cholerae (less than or equal to 12.5 ml/kg X h) received either somatostatin at a dose of 250 micrograms/h in saline (n = 12) or placebo (n = 10). The study drug was given for 12 h followed by a control period of the same duration. No difference in stool output was apparent between somatostatin- and placebo-treated groups. No side effects of somatostatin were observed. It is concluded that somatostatin is ineffective as an antidiarrheal agent in Asiatic cholera in humans.

Adult↗
PubMed1981

Influence of opiates on ion transport across rabbit ileal mucosa.

Opiates are commonly used as antidiarrheal agents, and endogenous opioids have been demonstrated in the intestine. It seemed important therefore to investigate the effects of morphine on ion transport across intestinal mucosa. In rabbit ileum in vitro morphine (2 x 10(-5) M) induced a significant fall in potential difference and short circuit current but did not influence tissue resistance. Dextromoramide (10(-5) M), an active opiate, mimicked the action of morphine, whereas the inactive isomer levomoramide (10(-5) M) had no effect. Morphine caused a significant increase in chloride absorption, due predominantly to a decrease in the serosa to mucosa flux. No change in sodium transport was detected, but the residual ion flux, possibly representing bicarbonate secretion, was enhanced. Similar response were observed with a synthetic enkephalin analogue (Me-Tyr-D-Met-Gly-Phe-Pro-NH2); but this was more potent than morphine, a significant electrical response being observed at a concentration as low as 10(-8) M. These electrical and ion transport responses to morphine were blocked by naloxone, an effect shown to be competitive in nature. The results suggest that opiate receptors exist in rabbit ileal mucosa and that these influence electrical and ion transport changes across the mucosa.

Animals↗
PubMed1983

Role of Roux-en-Y feeding jejunostomy for patients with acute head injury.

The total care of a patient with severe head injury is challenging and may extend for weeks, months, or even years. A major challenge of this care includes nutritional support: swallowing is impaired, aspiration accompanies gastric tube feeding, parenteral nutrition is limited to short term in hospital care, and needle jejunostomy or transabdominal jejunostomy are prone to inadvertent removal. The role of Roux-en-Y feeding jejunostomy was evaluated in 13 patients with acute head injury. Procedure related complications include prolapse of the ostomy (1 patient) and stoma-ischemia requiring revision (1 patient). The effect of ostomy tube feedings on gastric acid secretions was studied in five patients, and no significant change was noted when saline feeding was compared to blenderized diet feeding. Blenderized diet feedings were advanced gradually, and antidiarrheals were added as needed once gastrointestinal function returned. In conclusion, Roux-en-Y feeding jejunostomy provides an attractive, safe method for long-term enteral nutrition in the head injury patient. Easy replacement of the feeding tube facilitates nursing care, and the threat of acid-induced stress gastric bleeding is not enhanced.

Adult↗
PubMed1978

The control of acute diarrhea in a large industrial plant.

Diarrhea causes considerable absenteeism and loss of working time among employees in the United States. One hundred employees with acute diarrhea at a Ford Motor Company plant were studied for four months to determine if loperamide hydrochloride treatment would control diarrheal symptoms, reduce absenteeism due to the condition, and be well-tolerated. Diarrhea was controlled with a median dosage of three capsules (6 mg total dose) and a range of two to 12 capsules. Ninety-six percent of the subjects were controlled after the first day, 98% by the third day. A statistically significant number were symptom free at their last clinical visits. Side effects were generally minor in nature. Substantially more than 1,000 man-hours of lost time were saved because of the treatment. Known drug dependents did not suffer from CNS effects or "highs". Loperamide acts directly on the intestinal wall to inhibit excessive peristalsis, thereby providing prompt, effective relief, with normal bowel patterns observed in these patients. The simple, individualized dosage is patient-oriented, rather than based on a fixed regimen. Because of its rapid onset of action, effective control of symptoms, low dosage, and being well-tolerated, loperamide meets the criteria for an effective antidiarrheal agent in industry.

Absenteeism↗
PubMed1984

[Preventive measures against travel diarrhea].

The rules of exposition prophylaxis for traveler's diarrhea are strictly adhered to by only 2% of tourists in developing countries even though the benefits have been well documented. Vacationers generally prefer to take various types of drug prophylaxis despite the fact that a protective effect has only been proven for chemotherapeutic agents and for subsalicylate bismuth. Since their use is strictly limited, therapeutic self-medication becomes even more important. Glucose-electrolyte-solutions may initially increase the number of bowel movements and antidiarrheal agents tend to prolong illness in dysenteric patients. Chemotherapeutic agents are indicated only in select cases.

Anti-Bacterial Agents↗
PubMed1983

Giardiasis: a common, sexually transmissible parasitic diarrhea with pitfalls in diagnosis.

Giardia lamblia is the number one intestinal parasite in the United States. Symptoms of giardiasis include upper abdominal pain and distress, flatulence, nervousness, and diarrhea. Multiple stool specimens examined for ova and parasites by nonexpert parasitologists will frequently not provide the diagnosis, and special studies must then be done. Antibiotics, antidiarrheals, certain enema preparations, and oily laxatives can cause a temporary disappearance of parasites from the stool. Treatment of choice is a five-day course of quinacrine hydrochloride. Recently, attention has been brought to the fact that oral sex may be responsible for transmission in a significant number of cases of giardiasis.

Child↗
PubMed1980

Termination of pregnancy by intramuscular administration of 15 (S)-15-methyl-prostaglandin in F2 alpha.

The use of 15 (S)-15-methyl-prostaglandin F2 alpha for second-trimester termination of pregnancy, induction of labor in the presence of a dead or severely malformed fetus, and the management of molar pregnancy was investigated in 212 women. The dosage regime was 250 microgram of the prostaglandin analogue every 1 to 3 hours. Cumulative expulsion rates amounted to 94 and 97% after 24 to 36 hours, respectively. Gastrointestinal side effects occurred in 48% of the patients, and both the number and intensity of the episodes were significantly reduced by antiemetic and antidiarrheal drugs. No serious complications occurred.

Abortion, Induced↗
PubMed1981

The effects of chronic gastrointestinal medication on the fetus and neonate.

The adverse fetal and neonatal effects of chronic gastrointestinal medication have been reviewed. The major classes discussed are antiemetics, laxatives and antidiarrheal agents, antacids and cimetidine, drugs for irritable bowel syndrome, and drugs for inflammatory bowel disease. The evaluation given are tentative due to the lack of information on most of these drugs. It is hoped that research into the use of this diverse group of medications during pregnancy will be stimulated, so that the large gaps in our knowledge about them can be filled.

Abnormalities, Drug-Induced↗
PubMed1982

Clinical features of ciguatera fish poisoning: a study of the disease in the US Virgin Islands.

Clinical data were obtained on 33 patients involved in 27 episodes of ciguatera fish poisoning occurring during a 14-week period on St Thomas in the US Virgin Islands. All patients had gastrointestinal tract symptoms, with 30 patients (91%) complaining of diarrhea and 23 patients (70%) complaining of vomiting; these symptoms occurred early in the disease and were of short duration. Twenty-three patients (70%) complained of malaise, and 19 patients (58%) had pain and weakness in the lower extremities. Dysesthesias were noted by 19 patients (58%); the median duration of dysesthesias was two weeks or more, with symptoms present is some cases for more than two months. Cardiovascular signs and symptoms, including both hypotension and bradycardia were noted in some acute cases. Therapy included antidiarrheal and antiemetic agents, intravenous fluids, atropine, and pralidoxime chloride. Efficacy of pralidoxime therapy could not be established on the basis of our data.

Adolescent↗
PubMed1981

Interactions of reserpine and morphine on rat intestinal transit.

A study was designed to examine the interactions of reserpine and morphine on rat intestinal transit. Intestinal transit was determined in adult male rats by measuring the progression of an intraduodenally administered bolus (0.2 ml) or radioactive chromium (Na2(51)CrO4, 0.5 microCi) solution through the small intestine. Reserpine phosphate and morphine sulfate were administered either s.c. at 5 mg/kg or intracerebroventricularly (i.c.v.) at 50 and 30 micrograms (total dose), respectively. Reserpine given s.c. 16 hr before testing enhanced intestinal transit when given alone and diminished the intestinal antipropulsive effects of morphine given s.c. or i.c.v. Reserpine given i.c.v. 8 hr before testing did not alter the intestinal effects of morphine given s.c. or i.c.v. Neostigmine methylsulfate (0.1 mg/kg) given s.c. did not alter intestinal transit by itself but antagonized the inhibition of intestinal transit produced by morphine given s.c. Atropine sulfate (6 mg/kg) given s.c. did not affect intestinal transit by itself, nor did it antagonize the intestinal effects of s.c. administered morphine. However, atropine inhibited enhanced intestinal transit after reserpine given s.c. and restored the inhibitory effect of peripheral morphine on intestinal transit in animals pretreated with peripheral neostigmine or reserpine. The results suggest that reserpine inhibits the central and peripheral antidiarrheal effects of morphine by acting peripherally. Reserpine may antagonize the intestinal antipropulsive effects of morphine in the rat by directly or indirectly activating muscarinic cholinergic receptors.

Animals↗
PubMed1978

Interaction of loperamide and diphenoxylate with ethanol and methohexital.

The antidiarrheal drugs loperamide and diphenoxylate were tested for their ability to potentiate central nervous system depression induced by ethanol in mice and nethohexital in rats. Oral diphenoxylate potentiated the loss of righting reflex (hypnosis) at 10 mg/kg in mice and at 5 mg/kg in rats, doses which were considerably lower than those required to induce morphine-like behavior in mice and rats. Oral loperamide did not potentiate hypnosis. Increased incidence and duration of hypnosis was observed with loperamide only at very high, nearly toxic doses (100 mg/kg in mice and 80 mg/kg in rats) and these doses induced only nonspecific central nervous system depression. The failure of loperamide to potentiate the action of hypnotics confirms data from clinical trials which showed that loperamide is essentially free of central depressant effects when given orally.

Animals↗
PubMed1995

Functional colonic and anorectal disorders. Detecting and overcoming causes of constipation and fecal incontinence.

Evaluation of constipation and fecal incontinence begins with comprehensive history taking, which may include overcoming a significant psychosocial barrier. Before functional anorectal diseases can be controlled, the fundamental cause must be determined and any underlying disorder corrected. In constipation, a colonic or anorectal motility disorder is often the cause; about half of refractory cases are the result of obstructive defecation. In fecal incontinence, dysfunction of several anatomic or physiologic mechanisms may be the cause. Anorectal manometry is useful in assessment in both disorders. Other helpful tests are colonic-transit measurement in constipation and electrophysiologic tests and defecography in fecal incontinence. Treatment of constipation often includes dietary measures and use of laxatives or prokinetic agents; fecal incontinence may respond to bulking or antidiarrheal agents. In both disorders, some patients have responded to the recently described technique of neuromuscular conditioning with biofeedback. In some cases, surgical repair must be considered.

Constipation↗
PubMed1994

Strychnine-binding proteins in intestinal cells: novel brucine binding site with binding affinities for alkaloids.

The purpose of this work was to define the pharmacology of an intestinal epithelial [3H]strychnine binding site. Strychnine, brucine, verapamil and desmethoxyverapamil bind to small intestinal mucosal homogenates with nanomolar affinity at a site not related to the strychnine receptor, which is in the spinal cord. The antidiarrheal agents, fluperamide and loperamide, and several alkaloids have an order of magnitude lower affinity. Agents that bind to cytochrome P450IID6 also displace [3H]strychnine binding, which implies that the binding site may have some properties similar to the catalytic site of this cytochrome P450 enzyme.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Analysis of 16,16-dimethylprostaglandin E2-induced diarrhea in cecectomized rats.

The 16,16-dimethylprostaglandin E2 (dmPGE2)-induced diarrhea was analyzed in cecectomized rats prepared by resecting the cecum and its vasculature without disturbing the ileocecal junction. dmPGE2 (0.1-1.0 mg/kg, p.o.) dose-dependently increased the number of defecation episodes and induced a soft and watery stool in cecectomized rats. At 0.3 mg/kg, the diarrhea-inducing effects of dmPGE2 were more pronounced in cecectomized than in control rats. When given i.p., dmPGE2 (0.3 mg/kg) induced a watery stool in cecectomized and control rats with the same efficacy, although these effects were short-lasting as compared to oral administration. Castor oil (4 ml/kg, p.o.) also induced diarrhea, but did not produce a watery stool in cecectomized rats. There were no differences between cecectomized and control rats in basal small intestinal transits or in dmPGE2 (0.3 mg/kg, p.o.)-induced enhancements. Moreover, the basal and dmPGE2-induced jejunal net fluid transfers were the same in cecectomized and in control rats. On the other hand, the enhanced secretion of colonic fluid by dmPGE2, given intraluminally, was only half of that in control rats, whereas the colonic transit-enhancing effect of dmPGE2 in cecectomized rats was more pronounced than in control rats at 15 but not at 30 min after its administration. The basal colonic fluid contents and transits were the same in cecectomized and in control rats. Loperamide and morphine (0.1 and 1.0 mg/kg, s.c.) inhibited the dmPGE2 (0.3 mg/kg, p.o.)-induced diarrhea in cecectomized rats. N-methyllevallorphan (5 mg/kg, s.c.) completely antagonized the inhibitory effect of loperamide and partly antagonized the effect of morphine. These results suggest that oral administration of dmPGE2 induces a more pronounced secretory diarrhea in cecectomized than in control rats, probably due to the lack of the reservoir function of the cecum in the operated animals. This secretory diarrhea model is suitable for evaluating the antidiarrheal activity of drugs.

16,16-Dimethylprostaglandin E2↗
PubMed1976

Acute bacterial diseases.

The manner by which bacteria cause diarrhea has been clarified as a result of the understanding of mechanisms involved in fluid secretion. It is conceivable that many of the undiagnosed mass of diarrheal cases are in fact caused by E. coli or other organisms capable of eleborating an enterotoxin or of invading the epitehlial surfaces of the gastrointestinal tract. Confirmation of this concept would permit a better estimation of the importance of "viruses" in causing diarrhea. Proper treatment for bacterial diarrhea requires fluid replacement. Antibiotic therapy and antidiarrheal drugs need to be used with caution since they may worsen the diarrheal process or may complicate recovery.

Acute Disease↗
PubMed1994

[Effect of berberine on transit time of human small intestine].

Sorbitol was used as a test sugar for the determination of small intestinal transit time (SITT) by means of breath hydrogen test (BHT). After oral administration of 15g sorbitol, breath hydrogen increased markedly (delta H2 > 5 mumol/L) in 26 of 30 subjects. Following ingestion of a mixture of meglucamine diatrizoate and sorbitol by 18 subjects, SITT measured by BHT correlated closely with the simultaneously determined time for the meglucamine diatrizoate in reaching ileo-cecum. The BHT was used to investigate the effect of berberine on SITT in human. SITT in 20 healthy subjects was 71.10 +/- 22.04 min, SITT was significantly delayed to 98.25 +/- 29.03 min after oral administration of the 1.2g of berberine (P < 0.01). This result suggested that the antidiarrheal property of berberine might be mediated, at least in part, by its ability to delay the small intestinal transit.

Adult↗
PubMed1995

Gastrointestinal distribution of the prodrug loperamide oxide and its active drug loperamide in the dog.

Loperamide oxide is a prodrug of the effective antidiarrheal loperamide. Administration of this prodrug improves efficacy and tolerability. For better understanding of these effects, the absorption and gastrointestinal distribution of loperamide oxide and of its active drug loperamide were studied. Beagle dogs received a single oral dose of loperamide oxide or loperamide at 0.16 mg/kg. Plasma, gastrointestinal contents and tissues, and some other organs were obtained. Concentrations were determined by specific radioimmunoassays. Loperamide oxide was gradually converted to loperamide in the gastrointestinal tract. After administration of the prodrug, the systemic absorption of the active drug was lower and more delayed than after administration of loperamide itself. As a consequence, more loperamide was available in the contents and the mucosa of the gut, in particular in the lower part of the small intestine and in the large intestine. The higher levels of loperamide in mucosa may cause more pronounced and longer lasting antisecretory effects after administration of loperamide oxide. The results of this study are in line with the hypothesis that loperamide oxide is a site-specific prodrug that acts as a chemically designed controlled-release form of loperamide keeping a higher amount of the active drug for a longer time at the site of action in the gut wall.

Animals↗
PubMed1976

A double blind crossover comparison of loperamide with diphenoxylate in the symptomatic treatment of chronic diarrhea.

Loperamide, a novel antidiarrheal agent, was compared with diphenoxylate in a double blind crossover study of 23 patients with chronic diarrhea of various etiologies. Both agents were found to be capable of controlling or greatly reducing chronic diarrhea. Loperamide was superior to diphenoxylate in its abiltiy to decrease the frequency and improve the consistency of the stools, even at a 2.5-fold lower dose level.

Adult↗