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PubMed2002

Clinical and histological predictors of response to medical therapy in collagenous colitis.

OBJECTIVES: Collagenous colitis (CC) is an uncommon form of inflammatory bowel disease. The response to typical medical therapies (antimotility agents, 5-aminosalicylic acid [5-ASA], and corticosteroids) is variable. We aimed to determine if there are clinical or histological variables that can predict response to medical therapy. METHODS: All cases of CC were identified in three tertiary care medical centers. All charts of included patients were reviewed and clinical variables (age, gender, duration of symptoms, frequency of bowel movements, and the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) were recorded. Available histology slides were reviewed by one GI pathologist. Intraepithelial inflammation, epithelial loss or detachment, inflammation in the lamina propria, presence of eosinophilia, crypt inflammation, Paneth's cell metaplasia, and collagen layer thickness were recorded. Depending on their response to therapy, patients were divided into three groups: 1) spontaneous recovery or response to antidiarrheal agents alone, 2) response to 5-ASA agents, and 3) response to corticosteroids after failure of antidiarrheal agents and 5-ASA. RESULTS: Ninety-four patients with CC were identified. Of these, 62 patients were included. The median age was 58 (range = 20-85), and 88% were female. Among the histological parameters only the degree of inflammation in the lamina propria significantly differed between the three response groups (p = 0.007). Patients who required corticosteroids had greater inflammation. Among the clinical parameters age at presentation and use of NSAIDs significantly differed between groups. In the antidiarrheal group, patients tended to be more elderly, and in the corticosteroid group, more patients were on NSAIDs. CONCLUSIONS: 1) The degree of lamina propria inflammation can be used as a histological predictor to guide treatment in patients with CC. 2) Patients who responded to antidiarrheal agents or had spontaneous remissions were significantly older than those patients requiring 5-ASA compounds or corticosteroids. 3) Patients who were taking NSAIDs were more likely to require corticosteroid therapy, presumably reflecting more severe disease.

Adrenal Cortex Hormones↗

PubMed1993

Impact of an educational program on the treatment practices of diarrheal diseases among pharmacists and drugsellers.

The impact of an intervention program, measured by changes in the prescription of ORS, antibiotics and antidiarrheal drugs by those pharmacists and drugsellers after administering the proposed educational package was assessed. The results of the study indicated that, before the educational program started, ORS was prescribed by pharmacists for 31.4% and 15.7% of watery diarrhea and dysentery episodes, respectively. Only 18.9% and 13.3% of drugsellers gave ORS to assessors in case of watery diarrhea and dysentery. Antibiotics and antidiarrheal agents were prescribed extensively, watery and dysenteric diarrhea (84% and 56% for watery diarrhea by pharmacists and drugsellers; 92% and 60% for dysentery). Antidiarrheal drugs were used as frequently. After the educational program, the assessment of the prescription behavior of the pharmacists showed no change in ORS, antibiotics and antidiarrheal drugs prescribed to treat watery diarrhea. In dysentery, the effective percent change in prescribing ORS between pre- and post- intervention program was much higher in intervention group than the control group. For drugsellers, effective percent change in ORS usage in treatment of watery diarrhea was 11.8% compared with -7.7% in the control group. No such change was observed in treatment of dysentery. There was a slight significant change in behavior concerning use of antibiotics among subjects getting information by mail, compared to those who got full intervention, when the pre-intervention behavior, store type and treatment type was taken into account.

Anti-Bacterial Agents↗

PubMed1989

Pharmacists' self-medication for the travelers' diarrhea.

Visitors to developing areas of the world are at high risk for contracting travelers' diarrhea (TD). Despite proven effectiveness in the prevention of TD, prophylactic use of anti-diarrheal agents is controversial. Most authorities recommend against the routine use of drugs for the prevention of TD. This article presents data from surveys of pharmacists and their spouses participating in vacation-study tours to countries associated with a high risk of TD. Patterns of antidiarrheal drug use are compared with the recommended practices regarding both prophylactic and symptomatic therapy. Generally, the subjects in this study adhered closely to recommended practices. Nevertheless, although a majority employed dietary restrictions for TD prevention, 22.8 percent took antidiarrheal drugs prophylactically. Nearly half took antidiarrheal agents for symptomatic use. The ingredients most frequently mentioned matched current recommendations. Inappropriate practices included the use of prophylactic agents without dietary restrictions, and the use of antimotility agents prophylactically. Patterns of dietary and antidiarrheal drug use are compared, including intended versus actual, prophylactic versus symptomatic, and prescription versus nonprescription product use. The controversy regarding the use of prophylactic drug therapy for TD is discussed.

Diarrhea↗

PubMed1981

Influence of kaolin-pectin suspension on steady-state plasma digoxin levels.

The effect of a kaolin-pectin antidiarrheal mixture on steady-state plasma levels of orally administered digoxin in subjects receiving chronic digoxin therapy was evaluated when the antidiarrheal and the cardiac glycoside were given concomitantly and when two doses of antidiarrheal were given, one 2 hours before and the other 2 hours after digoxin. Although simultaneous administration of both products decreased peak digoxin levels by 36 per cent, 24-hour areas under the curve were reduced by only 15 per cent, indicative of a slight decrease in digoxin bioavailability. In contrast, when their times of administration were separated by 2 hours, no evidence of a drug interaction was noted. Hence, the effect of one or two doses of kaolin-pectin suspension on steady-state plasma levels of digoxin appears inconsequential in patients on chronic digoxin therapy. Saliva levels were poorly correlated with plasma levels, presumably because of complexation in the oral cavity.

Absorption↗

PubMed2004

Medical management of fecal incontinence.

Diarrhea and constipation are known risk factors for fecal incontinence. This report reviews how to diagnose and medically treat patients with chronic diarrhea, chronic constipation with overflow incontinence, and incontinence resulting from rectal mucosal prolapse secondary to hemorrhoids. Antidiarrheal agents (including loperamide, diphenoxylate, and difenoxin) and the tricyclic antidepressant amitriptyline improve continence in patients with diarrhea-associated incontinence. Other antidiarrheal agents are under investigation. The mechanism is believed to be decreased intestinal motility and stool frequency resulting in more formed stools. Increases in anal canal resting pressure may also contribute to improvement in continence. Adverse effects are constipation from excessive use. In addition to antidiarrheal drugs, fiber supplements may improve incontinence associated with diarrhea. Transient, benign cases of constipation usually respond to increasing fluid intake and dietary fiber, improving mobility, or eliminating the concurrent use of constipating drugs. For mild to moderate constipation, bulking agents, laxatives, and stool softeners are used cautiously so as not to excessively loosen stools and exacerbate anal incontinence. Laxatives have been shown to improve continence, possibly through the mechanism of eliminating fecal impaction. Prolapsing hemorrhoids may partially obstruct defecation and cause soilage from the passage of fecal material, mucus, or blood. With endoscopic banding, a ligator is attached to an endoscope and a tight band is placed around the enlarged vein, causing the hemorrhoid to thrombose.

Antidepressive Agents, Tricyclic↗

PubMed1999

Impact of protease inhibitors on the outcome of human immunodeficiency virus-infected patients with chronic diarrhea.

OBJECTIVE: The effect of protease inhibitors on the outcome of chronic HIV-related diarrhea is unknown. The aim of this study was to compare the response to treatment of chronic HIV-related diarrhea, recurrence of diarrhea, and survival in a large cohort of individuals taking protease inhibitors to the outcome in similar patients not receiving protease inhibitors. METHODS: We reviewed the medical records of all patients referred between October 1993 and October 1996 at Bellevue Hospital for endoscopic evaluation of chronic HIV-related diarrhea after negative stool examination. Only patients presenting after December 1995 received protease inhibitor therapy. Follow-up data were obtained from chart review and direct telephone contact. The success of antidiarrheal therapy was compared between protease inhibitor and nonprotease inhibitor groups for patients receiving pathogen-specific therapy and for those with no pathogens found on endoscopy. RESULTS: Two hundred eighty-two of 307 patients evaluated for chronic diarrhea were followed for a mean of 69.9+/-34.1 weeks. Patients receiving protease inhibitors had a significantly higher rate of successful response to antidiarrheal therapy (62.0% vs 33.5%, p < 0.001). Protease inhibitors were associated with a significant decrease in stool frequency (4.8+/-4.5 vs 3.4+/-4.6 bowel movements per day, p = 0.01), an increase in weight (2.4+/-5.9 vs -1.6+/-6.2 kg, p < 0.001), a decrease in recurrence of diarrhea (34.8% vs 15.3%, p = 0.02), and a longer mean survival (148 vs 118 weeks, p = 0.002). CONCLUSIONS: Protease inhibitors significantly improve the outcome of antidiarrheal therapy and survival in patients with chronic HIV-associated diarrhea.

AIDS-Related Opportunistic Infections↗

PubMed2001

Treatment responses in collagenous colitis.

OBJECTIVE: In the nearly 20 yr since collagenous colitis was first recognized, the results of therapies have not been systematically described in substantial numbers of patients. We have therefore conducted a retrospective analysis of 26 patients treated in this institution during the years 1991-1994. METHODS: Twenty-nine cases of collagenous colitis were obtained by review of biopsy specimens collected between 1991 and 1994 at The Mount Sinai Hospital. Each chart was reviewed for patient demographics, symptoms, coexisting conditions, specific therapies, and therapeutic outcomes. Additional data were obtained from telephone calls to patients when deemed necessary. Three patients were exeluded from the study because of lack of follow-up. Therapeutic outcomes were defined as follows: Complete Remission (CR): normalization of bowel function; Partial Remission (PR): 50% reduction in frequency of bowel movements; Failure: <50% reduction in frequency of bowel movements; or Relapse: return of symptoms after cessation of treatment. Median follow-up was 58 wk from time of diagnosis, with a range of 22-376 wk. RESULTS: The 26 patients (25 women, one man) had a mean age of 62 yr (range, 22-85 yr) at diagnosis. Of 26 patients, 22 responded to some form of therapy and one had spontaneous remission. Six of the responders ultimately remained in CR with no therapy. Twelve are maintained on 5-aminosalicylic acid (5-ASA) and or antidiarrheals to control symptoms. An additional six required prednisone throughout the follow-up period to remain in CR or PR. Two patients failed all therapy. CONCLUSION: Collagenous colitis is a treatable condition in most patients. We recommend initial therapy with antidiarrheals, followed by a trial of 5-ASA agent. A trial of 5-ASA in combination with prednisone should be attempted in patients refractory to 5-ASA alone, with subsequent attempts in the responders to taper prednisone and maintain remission with no therapy, if possible, or with 5-ASA and/or antidiarrheal agents if necessary.

Adult↗

PubMed1983

Role of alpha-2 adrenergic receptors in the control of diarrhea and intestinal motility.

Oral administration of clonidine blocked diarrhea induced in mice by castor oil, prostaglandin E2, 5-hydroxytryptophan and bethanechol. The antidiarrheal action of clonidine was blocked by yohimbine but not by naloxone, propranolol, prazosin or cimetidine, indicating involvement of the alpha-2 adrenergic agonist activity of clonidine. Other alpha-2 adrenergic agonists (naphazoline, guanabenz, ergometrine, alpha-methylnorepinephrine) were also effective antidiarrheal agents, but alpha-1 (methoxamine, phenylephrine) or beta (isoproterenol) adrenergic agonists were not. Clonidine also blocked normal defecation in mice, an effect which was antagonized by yohimbine. Intracerebroventricular injection of clonidine produced no antidiarrheal effect, suggesting a peripheral site of action. Clonidine inhibited the distension-induced peristaltic reflex in the isolated guinea-pig ileum, an effect which was antagonized by yohimbine. The profound inhibition of peristaltic flow rate was due largely to inhibition of the rate of peristalsis, although an inhibition of the force of peristaltic contractions also contributed. This suggests that the inhibitory effects of alpha-2 adrenergic agonists on intestinal motility are due to the presence of inhibitory alpha-2 adrenergic receptors located on the pacemaker neurons of the enteric nervous system as well as presynaptically on postganglionic neurons innervating intestinal smooth muscle cells.

Administration, Oral↗

PubMed1978

Pharmacokinetic evaluation of a drug interaction between kaolin--pectin and clindamycin.

The effect of a kaolin--pectin antidiarrheal suspension on the bioavailability of orally administered clindamycin was evaluated by model-dependent pharmacokinetic techniques. Each subject's serum clindamycin concentration--time data in the absence of the kaolin--pectin suspension were fitted to a one-compartment open model with first-order absorption and lag time. The resulting disposition parameters were used to construct individual Wagner-Nelson absorption profiles, expressed as the cumulative relative fraction of clindamycin absorbed versus time following combined antidiarrheal--antibiotic therapy. For each subject, absorption persisted to varying degrees through 14 hr. On the average, the half-time for absorption was prolonged 20-fold (from about 16 min to more than 300 min). In contrast, extrapolation of the individual time courses of relative absorption to infinity revealed that the antidiarrheal had no effect on the extent of clindamycin absorption.

Adult↗

PubMed1978

Influence of kaolin--pectin suspension on digoxin bioavailability.

The effect of a kaolin--pectin suspension on the bioavailability of orally administered digoxin was evaluated when both drugs were given concomitantly and when their time of administration was separated by 2 hr. Coadministration of the antidiarrheal with the cardiac glycoside delayed absorption of the latter and, at the same time, decreased by 62% the amount of drug absorbed. Intersubject variation in digoxin bioavailability also was increased more than twofold. When the kaolin--pectin suspension was given 2 hr before the cardiac glycoside, the digoxin absorption rate was not affected, although its relative extent of absorption was reduced by about 20%. In contrast, when the antidiarrheal was given 2 hr after digoxin, neither the rate nor the extent of absorption of the cardiac glycoside was perturbed. No change in the intersubject variability in digoxin bioavailability was noted whether the antidiarrheal was given 2 hr before or 2 hr after the cardiac glycoside.

Adult↗

PubMed1998

Comparison of the analgesic and intestinal effects of fentanyl and morphine in rats.

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.

Analgesics, Opioid↗

PubMed1996

Practice parameter: the management of acute gastroenteritis in young children. American Academy of Pediatrics, Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis.

This practice parameter formulates recommendations for health care providers about the management of acute diarrhea in children ages 1 month to 5 years. It was developed through a comprehensive search and analysis of the medical literature. Expert consensus opinion was used to enhance or formulate recommentations where data were insufficient. The Provisional Committee on Quality Improvement of the American Academy of Pediatrics (AAP) selected a subcommittee composed of pediatricians with expertise in the fields of gastroenterology, infectious diseases, pediatric practice, and epidemiology to develop the parameter. The subcommittee, the Provisional Committee on Quality Improvement, a review panel of practitioners, and other groups of experts within and outside the AAP reviewed and revised the parameter. Three specific management issues were considered: (1) methods of rehydration, (2) refeeding after rehydration, and (3) the use of antidiarrheal agents. Main outcomes considered were success or failure of rehydration, resolution of diarrhea, and adverse effects from various treatment options. A comprehensive bibliography of literature on gastroenteritis and diarrhea was compiled and reduced to articles amenable to analysis. Oral rehydration therapy was studied in depth; inconsistency in the outcomes measured in the studies interfered with meta-analysis but allowed for formulation of strong conclusions. Oral rehydration was found to be as effective as intravenous therapy in rehydrating children with mild to moderate dehydration and is the therapy of first choice in these patients. Refeeding was supported by enough comparable studies to permit a valid meta-analysis. Early refeeding with milk or food after rehydration does not prolong diarrhea; there is evidence that it may reduce the duration of diarrhea by approximately half a day and is recommended to restore nutritional balance as soon as possible. Data on antidiarrheal agents were not sufficient to demonstrate efficacy; therefore, the routine use of antidiarrheal agents is not recommended, because many of these agents have potentially serious adverse effects in infants and young children. This pracrtice parameter is not indended as a sole source of guidance in the treatment of acute gastroenteritis in children. It is designed to assist pediatricians by providing an analytic framework for the evaluation and treatment of this condition. It is not intended to replace clinical judgment or to establish a protocol for all patients with this condition. It rarely will provide the only appropriate approach to the problem. A technical report describing the analyses used to prepare this parameter and a patient education brochure are available through the Publications Department of the AAP.

Acute Disease↗

PubMed1998

Clinical outcome and bowel function following total abdominal colectomy and ileorectal anastomosis in the Oriental population.

UNLABELLED: Total abdominal colectomy with ileorectal anastomosis is a commonly performed surgical procedure. The postoperative outcome of these patients, however, has not been studied in detail in the Asian population. AIM: The purpose of this study was to analyze the functional outcome of patients following total abdominal colectomy and ileorectal anastomosis. METHOD: All patients subjected to a total abdominal colectomy with ileorectal anastomosis during a six-year period from February 1989 to October 1995 were reviewed. RESULTS: Sixty-six patients (male:female, 40:26) with a mean age of 55.2 (range, 20-88) years underwent total abdominal colectomy with ileorectal anastomosis. Median follow-up after surgery was 26 (range, 4-78) months. Indications for surgery were synchronous or metachronous tumors (18), complicated pancolonic diverticular disease (15), obstructed tumors with impending perforation (13), familial adenomatous polyposis (7), slow-transit constipation (6), and others (7). Mean operative time was 137 +/- 48 minutes. Mean postoperative hospitalization was 13.3 +/- 11.9 days. Time to first bowel movement and commencement of solid diet were 4.7 +/- 1.8 and 7.2 +/- 2.4 days, respectively. Four patients had prolonged postoperative ileus. Average stool frequencies per day were 5.5 at one week, 4.3 at one month, 3.9 at six months, 3.2 at one year, and 2.9 at two years postoperatively. Thirty-three patients (50 percent) required antidiarrheal treatment for a transient period, but none required long-term therapy. Ninety-seven percent of all patients rated the functional outcome as good to excellent, and 3 percent said it was fair. There was two perioperative mortalities. Five cases required re-laparotomy, three for anastomotic complications and two for hemoperitoneum. Five patients had recurrent admissions for adhesion colic, which resolved with nonsurgical therapy. Ten patients succumbed on follow-up, six to tumor recurrence, two to unrelated cancers (stomach and bladder), and three to medical conditions. CONCLUSION: The functional outcome of ileorectal anastomosis is generally rated as good to excellent by patients. Acceptable bowel function and control is regained within six months of the operation and levels off at one year after surgery, and no patient requires long-term antidiarrheal medication.

Adenomatous Polyposis Coli↗

PubMed2004

Green banana and pectin improve small intestinal permeability and reduce fluid loss in Bangladeshi children with persistent diarrhea.

To evaluate the effects of green banana and pectin (nondigestible, dietary sources of colonic shortchain fatty acids [SCFA]) on intestinal permeability, 57 boys (5-12 months) with persistent diarrhea (> or = 14 days) were given a week's treatment with a rice-based diet containing either cooked green banana (n = 19), pectin (n = 17), or rice diet alone (n = 21). Intestinal permeability was assessed before and after treatment by giving a lactulose-mannitol (LM) drink and measuring urinary recovery after 5 hr. Treatment with banana significantly (P < 0.05) reduced lactulose recovery, increased mannitol recovery, and decreased the LM ratio, indicating improvement of permeability. Pectin produced similar results. Permeability changes were associated with a 50% reduction in stool weights which correlated strongly (green banana, r2 = 0.84, pectin, r2 = 0.86) with the LM ratio. Green banana-derived and SCFA-mediated stimulation of colonic as well as small bowel absorption is responsible for their antidiarrheal effects. The antidiarrheal effects of green banana and pectin are mediated by improvement of small intestinal permeability in addition to their known colonotrophic effects.

Antidiarrheals↗

PubMed1999

Effect of wood creosote and loperamide on propulsive motility of mouse colon and small intestine.

To elucidate a mechanism of the antidiarrheal activity of wood creosote, its effect on the propulsive motility of mouse colon and small intestine was studied using a charcoal meal test and a colonic bead expulsion test. The effect was compared with that of loperamide. At an ordinary therapeutic dose, wood creosote inhibited the propulsive motility of colon, but not of small intestine. On the other hand, loperamide inhibited the propulsive motility of small intestine, but not of colon. The results indicate that at least a part of the antidiarrheal activity of wood creosote and loperamide is attributable to their antikinetic effect predominantly on colon of the former and predominantly on small intestine of the latter.

Animals↗

PubMed2001

The palliative effects of octreotide in cancer patients.

Octreotide is an extremely useful compound for palliative care physicians. It appears to be active in a number of different pain states and may be given by the spinal and intraventricular route. Its actions in reducing gut motility and secretions make it a valuable adjunct in the management of inoperable bowel obstruction. The same actions make it a potent antidiarrheal agent. Octreotide will often succeed where other antidiarrheal agents fail. Its ability to reduce gut secretions has led to its use in the treatment of fistulae. It has also been proposed as a useful drug in the management of cachexia and ascites. Most of the existing evidence is based on small numbers of case reports and further larger trials are necessary.

Antidiarrheals↗

PubMed1998

Gastrointestinal medications and breastfeeding.

Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

Adult↗

PubMed1999

Effects of Keishi-ka-shakuyaku-to (Gui-Zhi-Jia-Shao-Yao-Tang) on diarrhea and small intestinal movement.

The present study was conducted to determine the characteristics of the effects of Keishi-ka-shakuyaku-to (Gui-Zhi-Jia-Shao-Yao-Tang; TJ-60) on diarrhea. Significant repression was noted by TJ-60 at 1000 mg/kg, p.o. for diarrhea induced by pilocarpine, barium chloride or castor oil. Under normal conditions, TJ-60 did not influence small intestinal transit by its oral treatment even at 1000 mg/kg, however, it dose-dependently improved the acceleration of such transit caused by neostigmine. TJ-60 did not influence the resting tonus in isolated small intestine, but did selectively inhibit low frequency electrostimulated contractions. These results indicate that the antidiarrheal effects of TJ-60 may be due to the inhibition of excessively accelerated small intestinal movement, and that the inhibition of acetylcholine release by parasympathetic nerves is partly involved in the mechanism of this antidiarrheal action.

Animals↗