Diphenoxylate Research Articles

Wei Chang An pill regulates gastrointestinal motility in a bidirectional manner

Context Wei Chang An (WCA) is a commercial prescription developed for the coordination of gastrointestinal movement. Objective To investigate the role of WCA in the regulation of diarrhoea and constipation in rats. Material and methods The diarrhoea and constipation models were prepared by gavage of Folium senna and diphenoxylate hydrochloride. Rats were randomized equally (n = 6) into the normal group given saline daily, the positive group given Pinaverium Bromide (13.5 mg/kg) or Sennoside A (0.1 mg/kg) and three WCA-treated groups (22, 44, and 88 mg/kg) by gavage daily for 7 consecutive days. The effects of WCA were assessed by a series of faecal symptoms and histopathology. Gastrointestinal parameters were determined by ELISA. The effect of WCA on gastrointestinal tissues was evaluated by strip assay. Expression of ROCK-1 and MLCK was measured by RT-PCR and Western blotting. Results Data from Bristol stool form scale, diarrhoea index, visceral sensitivity, defaecation time, and intestinal propulsive rate showed that WCA protected rats against diarrhoea and constipation (p < 0.01). The up-regulation of Substance P and 5-hydroxytryptamine in diarrhoea rats and down-regulation of Substance P and vasoactive intestinal polypeptide in constipation rats were inhibited by WCA (p < 0.05). WCA stimulated the gastrointestinal strip contractions but inhibited ACh-induced contractions (p < 0.01). The decreased ROCK-1 and MLCK expression in diarrhoea rats and increased in constipation rats were suppressed by WCA (p < 0.01). Conclusions WCA has both antidiarrhea and anti-constipation effects, suggesting its bidirectional role in gastrointestinal modulation, and providing evidence of WCA for irritable bowel syndrome treatment.

Diphenoxylate hydrochloride and atropine sulfate overdose in an infant presenting as respiratory failure

A fixed-dose combination of diphenoxylate hydrochloride and atropine sulfate marketed widely as oral tablets, is one of the most frivolously used drugs to treat diarrhea in adults. Its safety and efficacy in children younger than 2 years are not known. In this case, we came across a 45-day-old infant being maltreated with adult dose of the drug, for diarrhea, by a local charlatan, which landed him in the emergency room with lethargy, altered sensorium, and type 2 respiratory failure and ultimately had to be salvaged by mechanical ventilation. This case describes the life-threatening adverse effects of an adult drug on the pediatric age group.

Effect of Angelica sinensis radix on colonic morphology and mucus secretion of experimental XuexuBianmi model mice

To study the effects of Angelicaesinensis radix (Danggui) decoction on the therapeutic action and the colonic morphology and mucus secretion in XuexuBianmi model mice. Sixty Kunming mice, maleandfemaleinhalf, were randomly divided into six groups according to gender and weight (n=10):normal control group, XuexuBianmi model group, positive control group, and high-dose, middle-dose and low-dose Danggui groups. Except the normal control group, the mice in the rest groups were orally administrated with diphenoxylate (DPN) and subcutaneously injected with acetylphenyhydrazine (APH) and intraperitoneally injected with cyclophosphamide (CPA) to copy XuexuBianmi model. Fromthe 14th day, the mice in Danggui groups were orally administered with different doses of Danggui decoction (16.67、8.33、4.17 g/kg), the mice in positive control group were orally administered with Changtongshu granule (5 g/kg), the mice in XuexuBianmi model group were administered with normal saline (NS) at the same volume (10 ml/kg), once a day for consecutive 28 days. The general status were observed, the first black defecation time (FBDT), the water content in stool and in colon in mice of all groups were tested. And the colon tissue was stained with hematoxylin-eosin (HE) and AB-PAS to observe the changes of colonic morphology and the mucus secretion. Compared with the normal control group, there appeared the XuexuBianmi syndromes in model group as follows, the defecation time (FBDT) was significantly prolonged, the water contentinstool and in colon were decreased (P<0.01), the colonic mucosa and gland were atrophied, mucous membrane layer was thinned (P<0.01), mucus secretion was decreased. Compared with the XuexuBianmimodel group, the Xuexu and Bianmi syndromes were improved, the FBDT was significantly shortened (P<0.05, P<0.01), the water content of colon was increased in the three groups of Danggui decoction (P<0.05, P<0.01). The water content of the stool was obviouslyincreased in groups of 16.67and 8.33kg.dDanggui decoction (P<0.05). The atrophy of colon mucosa and gland was improved, the mucus secretion was increased, and the colon lubrication function was improved in the three groups in different doses of Danggui decoction. Dangguican improve the mucosal atrophy, and increase the secretion of colonic mucus, then the stool is softened and promoted to discharge.

Experimental study of Bisacodyl in the treatment of slow transit constipation model rats

To explore the efficacy and the mechanism of Bisacodyl in treating slow transit constipation model rats. A total of 30 healthy rats were enrolled. Twenty rats received intragastric diphenoxylate to develop slow transit constipation (STC) model, and 10 untreated rats were set as blank control. STC rats were subdivided into two groups: STC Bisacodyl group (fed with Bisacodyl) and STC control group (common feed). Body weight, number and dry weight of faeces, and intestinal transit time were compared among 3 groups. Interstitial cells of Cajal(ICC) and c-Kit protein expression were measured by immunohistochemical staining. Restults Compared to blank control rats, at 100-day of receiving intragastric diphenoxylate, above 20 rats presented the decrease of body weight and feces number, the increase of dry weight of faeces, and the delay of intestinal transit time, indicating the successful establishment of STC rat model. One month after feeding, compared to STC control group, STC Bisacodyl grap had an increased feces number[(36.6±6.8) pill/day vs. (26.8±6.0) pill/day], decreased dry weight of feces [(150.6±10.5) mg/pill vs. (171.6±16.3) mg/pill] and shortened intestinal transit time [(416.9±50.6) minutes vs. (495.3±66.8) minutes], and the differences were statistically significant(all P<0.05). Dissolution of ICC basement membrane, damage of connection between ICC and surrounding cells, and atrophy of ICC nucleus structure were found in STC control rats. ICC (8.20±1.92 per field] and c-Kit expression (12.68%±2.59% ) in STC control rats were significantly lower than those in blank control rats(36.00±6.25 per field and 71.50 %±8.27%) (P=0.000). Compared to STC control group, the connection between ICC and surrounding cells enhanced obviously, ICC (18.80±3.70 per field) and c-Kit expression (45.91%±6.80%) were significantly higher in STC Bisacodyl group (all P=0.000). Bisacodyl treatment can relieve STC symptoms, which may be associated with increased ICC number and c-Kit protein expression.

Clinical efficacy of laparoscopic radical resection for rectal cancer using transanal telescopic anastomosis

Objective To investigate the clinical efficacy of laparoscopic radical resection for rectal cancer using transanal telescopic anastomosis. Methods The clinical data of 52 patients with low rectal cancer who underwent laparoscopic radical resection using transanal telescopic anastomosis at the General Hospital of Beijing Military Command from March 2010 to December 2014 were retrospectively analyzed. Patients with T2N1 stage received the routine chemotherapy after operation. The evaluating indexes of clinical efficacy included operation time, volume of intraoperative blood loss, number of lymph nodes dissection, time to anal exsufflation, pelvic drainage-tube removal time, duration of hospital stay, postoperative complications, marginal states, postoperative anal defecation function and local recurrence of tumors. Patients were followed up by outpatient and inpatient examinations and telephone interview up to March 2015, and follow-up included the occurrence of complications, postoperative anal defecation function and local recurrence of tumors. Measurement data with normal distribution were presented as ±s, and measurement data with skew distribution were described as M (range). Results Fifth-two patients underwent transanal laparoscopic sphincter-preserving radical resection using telescopic anastomosis successfully. The operation time, volume of intraoperative blood loss, number of lymph nodes dissection, time to anal exsufflation, pelvic drainage-tube removal time and duration of hospital stay were (150±36)minutes, (16±9)mL, 12±9, (2.0±1.5)days, (5.0±2.0)days and (9.0±2.5)days, respectively. One patient with anastomotic fistula was cured by transverse colostomy, with a stoma healing 3 months later. The postoperative pathological examination showed there were 46 patients with high- and moderate- differentiated adenocarcinomas and 6 patients with poor-differentiated adenocarcinomas, and T1-2N0M0 stage was detected in 29 patients and T2N1-2M0 stage in 23 patients. The distal and circumferential resection margins of tumors were negative. The defecation of 6-9 times/day in 52 patients after postoperative early food intake was reduced to 3-6 times/day after taking orally compound diphenoxylate tablets 2 pills each time and 3 times a day for 2-3 days. Twenty-three patients with T2N1 stage or above underwent postoperative routine chemotherapy. Fifth-two patients were followed up for a median time of 29.7 months (range, 3.0-51.0 months). The defecation control was improved remarkably at 2-3 months after operation. There was 94.2%(49/52) of patients with Kirwan grade 1of anal defecation function at postoperative month 12, and anal defecation function had basically returned to normal. There were 3 patients with Kirwan grade 2 of anal defecation function. One patient complicated with anastomotic stenosis had remission by anal expansion treatment during follow-up. Patients had no local recurrence of tumor with good quality of life. Conclusion Laparoscopic radical resection for low rectal cancer using transanal telescopic anastomosis is safe and feasible without abdominal incision, with a good cosmetic effect and satisfactory short-term outcome. Key words: Rectal neoplasms; Radical resection; Telescopic anastomosis; Laparoscopy

The empirical pharmacodynamics study of compound orange peel bamboo shavings formula capsules in chemical constipation

Objective To explore the effect of compound orange peel bamboo shavings formula capsules on constipation by examining on chemical constipation mice. Methods Constipation was induced by oral administration of diphenoxylate and ondansetron. Mice were fed with compound orange peel bamboo shavings formula capsule at the doses of 3.2, 1.6 and 0.8 g/kg, respectively. Results The middle dose and high dose of compound orange peel bamboo shavings formula capsule shortened the start time of defecation, and increased fecal pellets number and wet weight in the diphenoxylate-induced constipated mice or the ondansetron-induced constipated mice (P< 0.05). Conclusion Compound orange peel bamboo shavings formula capsule produces a laxative activity against diphenoxylate-induced constipated mice or ondansetron-induced constipated mice. Key words: Compound orange peel bamboo shavings formula capsules; Constipation; Diphenoxylate; Ondansetron

Antidiarrheal and analgesic effects of Dingguier paste on the mouse models

Objective To observe the antidiarrheal and analgesic effects of Dingguier paste on the mouse. Methods Tho diarrhea mouse models were made by senna leaf or castor oil to detect the antidiarrheal effect of Dingguier paste combination with other drugs. The hot plate test and acetic acid test were used to observe the analgesic effect of Dingguier oral medicine and Dingguier paste in combined use with other drugs. Results Compared with senna leaf model group, Dingguier paste low-dose, middle-dose, high-dose combined with diphenoxylate, Bupi-Yichang pill and Dingguier oral medicine group could decrease the number of feces in 2 h [Number of each group feces was（0.50±1.27）, （2.27±2.90）, （1.18±1.83）;（2.00±2.26）, （3.40±2.17）,＆amp;nbsp;（3.82±1.72）;（0.73±1.56）, （1.91±2.95）, （2.55±2.11）]. Dingguier paste low-dose and high-dose combined with diphenoxylate could decrease the number of feces in 4h [Number of each group feces was （6.70±2.11）, （6.27±3.20）]. Dingguier oral group decrease the number of feces in 6h [Number of feces was （6.91±2.77）]. Compared with castor oil model group, Dingguier paste low-dose combined with diphenoxylate could obviously decrease the number of feces in 2 h, 4 h and 6 h [Number of each group feces was（0.45±0.82）, （0.45±0.82）, （4.27±2.15）]. Dingguier paste middle-dose combined with diphenoxylate could decrease the number of feces in 6 h [Number of feces was （4.64±2.45）]. Dingguier oral group decrease the number of feces in 2 h, 4 h, 6 h [Number of each group feces was （0.45±0.82）, （2.91±2.07）, （4.27±2.15）].Compared with normal group, the threshold of pain stimulated by hot plate of the Dingguier paste each dose combined with rotundin could increased remarkable after 30 min, 60 min, 90 min and 120 min[The time of Dingguier paste low-dose was（52.32 ± 17.29）s, （56.24 ± 12.48）s, （57.28 ± 6.61）s, （58.58 ± 4.70）s; the time of Dingguier paste middle-dose was （48.27±19.35）s, （54.92±12.59）s, （55.91±11.48）s, （55.15±12.49）s;the time of Dingguier paste high-dose was （49.15±15.69）s, （56.24±11.89）s, 60 s is（59.08±2.93）s]. Compared with normal group, the eclipse time of pain irritated by acetic acid of the Dingguier paste middle-dose combined with indomethacin could increased remarkable（14.72±5.99）min, the writhing frequency could decrease of the Dingguier paste each dose combined with indomethacin[Number of each dose writhing frequency was （7.62±8.31）, （3.62± 6.14）, （11.25±9.46）]. Conclusion Dingguier paste in the combination use with other drugs and Dingguier oral medicine may have some antidiarrheal and analgesia effects. Key words: Dingguier paste; Diphenoxylate; Rotundin; Indomethacin; Antidiarrheal; Analgesia

Mesalamine Is Ineffective in Collagenous Colitis

The goal of treatment in collagenous colitis is relief from diarrhea. Nonspecific therapies including loperamide, diphenoxylate, cholestyramine, and bismuth are useful, and anti-inflammatory drugs are often used, including systemic corticosteroids, budesonide, 5-aminosalicylates and, in challenging cases, even immunomodulators and agents such as cyclosporine. Of these, evidence of efficacy is strongest for budesonide. Now, investigators have assessed the efficacy and tolerability of mesalamine in …

Alterations of Cajal cells in the colon of slow transit constipation rats

To investigate the association of expression of c-kit (marker of interstitial cells of Cajal, ICC) in colon with slow transit constipation (STC) in rats. Slow transit constipation (STC) rat model was induced by intragastric administration of compound diphenoxylate. Western blotting was used to measure the expression of c-kit in colon of STC rats (model group) and normal rats (control group). Gray scale ratio of c-kit to β-actin was used as the relative quantity of c-kit. Fecal quantity per day of STC group was (1.3±0.7) g/100 g, significantly lower than that in normal rats [(1.6±0.9) g/100 g, t=10.798, P<0.05]. In model rats, the time of discharge of the first black fecal was (461.6±150.8) min, significantly longer than that in normal rats [(351.3±119.9) min, t=2.291, P<0.05]. Western blotting revealed that the average values of gray scale ratio of c-kit in proximal colon were 0.277±0.077 and 0.576±0.081 (t=10.719, P<0.05), in distal colon were 0.280±0.075 and 0.571±0.079 (t=10.700, P<0.05) in model group and control group respectively. Down-regulation of c-kit expression in proximal colon and distal colon is associated to the pathogenesis of slow transit constipation in rats.

Development and Validation of Headspace Method for Determination of Residual Solvents in Diphenoxylate Hydrochloride Bulk Drug

Organic volatile impurities by Headspace GC method was developed and validated for Diphenoxylate hydro- chloride bulk drug for its seven residual solvents. Analysis was performed on Perkin Elmer HS 40 system with auto injector. Carrier gas Helium was used with constant flow rate of 2.5mL/min as carrier gas and the separation of residual solvents were achieved on DB-5 column. The thermostat temperature was 125 °C for 20 minute for each vial and after the equilibration the vials were pressurized and injected on GC column. FID detector was used for detection. The parameter for which the method was validated included specificity, limit of detection and quantification, linearity, precision, accuracy and robustness. The method was successfully used to quantify the levels of specified limit for residual solvents in Diphenoxylate hydrochloride bulk drug.

Development and Validation for Reverse Phase High Performance Liquid Chromatographic Method for Simultaneously Determination for Diphenoxylic Acid, Nitrileamide and Bromdiphenyl Butoro Nitrile in Diphenoxylate Hydrochloride Bulk Drug

Development and Validation for Reverse Phase High Performance Liquid Chromatographic Method for Simultaneously Determination for Diphenoxylic Acid, Nitrileamide and Bromdiphenyl Butoro Nitrile in Diphenoxylate Hydrochloride Bulk Drug

Diphenoxylate overdose

Diphenoxylate overdose

Medicine poisoning easily overlooked in children

Naphazoline,Diphenoxylate, Over-the-counter (OTC) cough and cold medications, widely used for the symptomatic relief of nasal obstruction, diarrhea or common cold symptoms. But these medicines might cause poisoning even if utilized in recommended doses for treatment. The side effects of these medicines were neglected when they were used much more commonly. The clinical manifestation of these medicine poisoning were delitescence and children' s parents couldn't provide the whole history, so these medicine poisoning were often misdiagnosis, even lead to treatment failure. We explore the toxicities of these medicines ,discuss their mechanisms and clinical manifestation, and suggest why physicians should be more vigilant in specifically inquiring about them when evaluating an ill child. Key words: Naphazoline; Diphenoxylate; Over-the-counter cough and cold medications; Poisoning; Children

Antibacterial, antidiarrhoeal and ulcer-protective activity of methanolic extract of Spondias mangifera bark

PURPOSE: To evaluate Spondias mangifera bark for indomethacin-induced ulcer protective and castor-oil induced antidiarrhoeal activity. METHODS: The extracts of S. mangifera were tested for castor-oil induced diarrhea, and intestinal fluid accumulation and propulsion in rats using diphenoxylate hydrochloride and atropine as standard drug. The effect of the extracts on indomethacin-induced ulceration in rats was also evaluated. using cimetidine as positive control. In-vitro antibacterial activity of methanolic and aqueous extract was also evaluated against Escherichia coli, Salmonella typhimurium and Vibrio cholerae bacteria. RESULTS: There was a significant (p < 0.01) inhibition activity against castor oil induced diarrhoea and fluid accumulations in rats when tested at 100 and 200mg/kg. The extracts also showed significant (p < 0.01) reduction in intestinal propulsion in charcoal meal test in rats. The methanol extract inhibited the ulcerogenic effect of indomethacin and good antibacterial activity. CONCLUSION: S. mangifera possesses significant antidiarrhoeal, ulcer protective and antibacterial activities. Keywords: Antidiarrhoeal; Antibacterial; Spondias mangifera bark; Ulcer protective effect.

Effect of Fructus Aurantii Immaturus decoction on defecating function of constipated mice induced by Compound Diphenoxylate

Objective To study the effect of Fructus Aurantii Immaturus Decoction on defecating function of constipated mice.Methods Constipation mice models were induced by Compound Diphenoxylate.Defecating effects of Fructus Aurantii Immaturus on normal and constipation mice were observed.Results Middle and high dose of Fructus Aurantii Immaturus decoction could increase impelling rate of small intestine,shorten the time for the first dark stools(P<0.05 or P<0.01).and add the amount of dark stools within 6 hours(P<0.01).Conclusion Fructus Aurantii Immaturus has the functions of loosening bowel to relieve constipation. Key words: Fructus Aurantii Immaturus; Constipation; Propelling rate of small intestine; Mice

Traveling Internationally: Avoiding and Treating Travelers' Diarrhea

Traveling Internationally: Avoiding and Treating Travelers' Diarrhea

Cerebral manifestation in compound Diphenoxylate poisoning:a case report

Cerebral manifestation in compound Diphenoxylate poisoning:a case report

Loperamide Use for Acute Infectious Diarrhea in Children: Safe and Sound?

Loperamide Use for Acute Infectious Diarrhea in Children: Safe and Sound?

Diphenoxylate Hydrochloride Dependency

Diphenoxylate Hydrochloride Dependency

Study of antidiarrheal activity of &lt;i&gt;Hydrocotyle javanica&lt;/i&gt; in mice

The effect of the methanolic leaf extract of Hydrocotyle javanica (family Hydrocharitaceae) was investigated in mice to evaluate its antidiarrheal activity on magnesium sulfate (MgSO 4 ) induced diarrhea and gastrointestinal motility. Hydrocotyle javanica , at doses of 50 mg/kg and 100 mg/kg, was tested for its effect on fecal output in magnesium sulfate induced diarrhea in albino mice and the results (percentage of animals showing diarrhea) were compared with those of diphenoxylate hydrochloride, a standard allopathic antidiarrheal drug. Hydrocotyle javanica (at a dose of 100 mg/kg) inhibited the magnesium sulfate induced diarrhea and also reduced gastrointestinal motility in mice. The results indicate that the leaf extract significantly reduced diarrhea in mice with a reduction in weight of stools. Keywords : Hydrocotyle javanica , antidiarrheal, magnesium sulphate, diphenoxylate hydrochloride, gastrointestinal motility, methanolic leaf extract The East and Central African Journal of Pharmaceutical Sciences Vol. 8(2) 2005: 31-34