Effect Of Bisacodyl Research Articles

Effect of bisacodyl on rats with slow transit constipation.

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Influence of chronic bisacodyl treatment on the effect of acute bisacodyl on water and electrolyte transport in the rat colon.

Excessive or unnecessary taking of laxatives leads to a vicious circle with perpetuation of laxative abuse and increase of laxative dosage, accompanied by severe clinically evident disturbances. It was investigated in rats whether chronic administration of bisacodyl reduces the effects of acute bisacodyl administration on net water and electrolyte flux in the rat colon transport in-vivo. After chronic pretreatment with bisacodyl had been given for 21 days (3 mg and 10 mg kg-1 day-1), net water and sodium absorption was found to be decreased whereas potassium secretion was increased. After 21 days of pretreatment, the effect of acute bisacodyl (10 micrograms ml-1 intraluminal) on net water and sodium transport was reduced whereas the effect on potassium secretion remained unchanged. Serum and erythrocyte levels of sodium and potassium remained unchanged in chronically pretreated rats. Serum aldosterone levels were enhanced two fold. It is concluded that under the experimental conditions described, chronically administered bisacodyl leads to elevated serum aldosterone which counteracts the effect of bisacodyl on net water and sodium transport but acts synergistically with bisacodyl on the effect on potassium loss.

Timing and Frequency of Bowel Activity in Patients Ingesting Sodium Picosulphate/Magnesium Citrate and Adjuvant Bisacodyl for Colon Cleansing Before Colonoscopy

Despite the wealth of research investigating bowel cleansing efficacy, there are very little data on the timing or frequency of bowel movements after each agent is ingested. To examine the effect of each component of a three-day combined sodium picosulphate⁄magnesium citrate (PSLX) and bisacodyl regimen on the timing and frequency of bowel activity in patients undergoing colonoscopy. Outpatients booked for colonoscopy were asked to complete a diary of their bowel preparation that tracked the timing of bowel movements. Bowel preparation quality was assessed using the Ottawa Bowel Preparation Scale. Bowel activity was compared with baseline and correlated with colon cleansing. Subgroup analysis was performed examining the effect of timing of the procedure and split-dose regimens. One hundred patients undergoing colon cleansing received bisacodyl 10 mg at 17:00 three days and two days before the day of colonoscopy. In one group, both sachets of PSLX were given the night before colonoscopy, while the second group, whose colonoscopies were scheduled after 11:00, ingested one sachet the night before and the second sachet at 06:00 on the day of colonoscopy. Patients had a mean of 1.7 bowel movements per day in the seven days before starting the cleansing regimen. Both doses of bisacodyl tablets resulted in a significant increase in the mean number of bowel movements compared with baseline (3.3⁄day first dose; 3.8⁄day second dose [P=0.03 and 0.001, respectively]). Each dose of PSLX also resulted in a significant increase in bowel movement frequency compared with baseline, with means of 4.4, 6.3 and 4.5 bowel movements after each dose. The mean time to the final bowel movement following the second sachet of PSLX was 8.9 h when taken the night before, and 3.9 h when taken the morning of the procedure. Bowel preparation quality significantly correlated with bowel frequency when total bowel movements were considered and when only the effects of bisacodyl were accounted for (P<0.01 for each). These data demonstrate that the addition of bisacodyl before PSLX ingestion has a significant additive effect on bowel frequency and correlates with bowel cleansing quality. The timing of the resulting bowel movements have practical implications for sleep and travel times to endoscopy suites.

Effects of bisacodyl on ascending colon emptying and overall colonic transit in healthy volunteers

The mechanism of action of bisacodyl in the unprepared human colon remains unclear. To evaluate the effect of oral bisacodyl on the overall and regional colonic transit in humans. In a double-blind, randomized, placebo-controlled study of 25 healthy participants, effects of oral bisacodyl (5 mg p.o. per day) and placebo on colonic transit were compared. A validated scintigraphy method was used to measure colonic transit. The primary transit endpoints, ascending colon emptying t(1/2) and geometric centre of colon isotope at 24 h (overall transit), were compared (Wilcoxon rank sum test). There were significant treatment effects on ascending colon t(1/2), with the bisacodyl group demonstrating accelerated emptying [median 6.5 h, interquartile range 5.0-8.0 h] relative to the placebo group [11.0 h (7.0-17.1); P = 0.03]. Numerical differences in colonic geometric centre 24 h [bisacodyl median 3.0 (2.2-3.8), placebo 4.0 (3.1-4.6)] were not significant (P = 0.19). There were no significant differences observed in geometric centre 4 h. Oral 5 mg bisacodyl accelerates ascending colon in the unprepared colon in healthy adults; this action may contribute to the drug's efficacy in constipation.

Effect of bisacodyl on postoperative bowel motility in elective colorectal surgery: a prospective, randomized trial

Postoperative ileus is a common condition after abdominal surgery. Many prokinetic drugs have been evaluated including osmotic laxatives. The data on colon-stimulating laxatives are scarce. This prospective, randomized, double-blind trial investigates the effect of the colon-stimulating laxative bisacodyl on postoperative ileus in elective colorectal resections. Between November 2004 and February 2007, 200 consecutive patients were randomly assigned to receive either bisacodyl or placebo. Primary endpoint was time to gastrointestinal recovery (mean time to first flatus passed, first defecation, and first solid food tolerated; GI-3). Secondary endpoints were incidence and duration of nasogastric tube reinsertion, incidence of vomiting, length of hospital stay, and visual analogue scores for pain, cramps, and nausea. One hundred sixty-nine patients were analyzed, and 31 patients discontinued the study. Groups were comparable in baseline demographics. Time to GI-3 was significantly shorter in the bisacodyl group (3.0 versus 3.7 days, P = 0.007). Of the single parameters defining GI-3, there was a 1-day difference in time to defecation in favor to the bisacodyl group (3.0 versus 4.0 days, P = 0.001), whereas no significant difference in time to first flatus or tolerance of solid food was seen. No significant difference in the secondary endpoints was seen. Morbidity and mortality did not differ between groups. Bisacodyl accelerated gastrointestinal recovery and might be considered as part of multimodal recovery programs after colorectal surgery.

Effect of Colchicine and Bisacodyl on Rat Intestinal Transit and Nitric Oxide Synthase Activity

Background: Bisacodyl and colchicine affect smooth-muscle contractility, intestinal water, and electrolyte transport. Nitric oxide (NO) stimulates intestinal electrolyte secretion and has an important role as a mediator of intestinal motility. We therefore studied, in rats, the effects of these agents on nitric oxide synthase (NOS) activity and gastrointestinal transit. Methods: Rats were treated with bisacodyl (10 mg/kg intragastrically) or colchicine (5 mg/kg intraperitoneally) with or without pretreatment with ketotifen (1 mg/kg intragastrically). Rats were killed after 1, 2, and 4h. The intestine was isolated and rinsed, the mucosa scraped, and NOS activity determined. In all rats small-intestinal transit was measured 15 min after intragastric administration of charcoal. Results: Bisacodyl (10 mg/kg) and colchicine (5 mg/kg) induced a significant decrease in jejunal NOS activity. Pretreatment with the mast cell stabilizer ketotifen, which has been shown to attenuate the increased permeability induced by NO inhibition, prevented the decrease in colonic and jejunal NOS activity induced by bisacodyl and colchicine. Bisacodyl and colchicine significantly decreased intestinal transit time. Their effect on transit time was similar to that induced by intravenous administration of NG-nitro-L-arginine methyl ester (10 mg/kg). Conclusions: It is suggested that the effect of bisacodyl and colchicine on intestinal transport is, at least partly, mediated through NO inhibition.

Effects of sennosides A + B and bisacodyl on rat large intestine.

Oral and intracecal administration of bisacodyl or sennosides A + B (10-100 mg/kg each) to rats induced a similar quantity of soft feces within 24 h and a similar acceleration of large intestinal transit time, but in each case bisacodyl had a prolonged action. Net fluid absorption in the perfused rat colon was reduced to a comparable extent by local bisacodyl in 1/10 of the molar concentration of rhein, an active metabolite of sennosides; recovery was delayed after bisacodyl. These results show that the time course of the laxative action of both drugs is different, probably attributable to their different pharmacokinetics. Both drugs influence colon motility as well as colonic secretion, but fluid secretion may contribute more to the laxative effect of bisacodyl than to that of sennosides.

Effect of bisacodyl on intestinal electrolyte and water net transport and transit. Perfusion studies in men.

The effect of bisacodyl on intestinal electrolyte, glucose, and water transport, and transit was studied in 6 healthy volunteers by intestinal perfusion. A 5-lumen tube with an occluding balloon allowed constant perfusion (10 ml/min) of 30 cm of the upper jejunum and a rapid collection of the perfusate free of contaminants. A phenol red bolus was injected into the tube and its passage through the test segment was calculated by dye dilution formula. A 1-hour control period was followed by a test period with 6 mg/h bisacodyl and followed by 2 other 1-hour control periods. Net absorption of Na+ (0.35 +/- 0.08 mmol/min) and water (1.7 +/- 0.6 ml/min) changed to net secretion (Na+ -0.93 +/- 0.3 ml/min; water -6.6 +/- 1.9 ml/min), glucose absorption decreased from 25.4% +/- 1.1 to 6.3 +/- 0.5 mg/min and K secretion was enhanced. 62 +/- 2.1% of bisacodyl was absorbed in the 30-cm jejunal segment. Mean transit time decreased from 8.5 +/- 1 to 4.4 +/- 0.7 min and mean flow rate increased from 8.4 +/- 0.6 16.6 +/- 1.9 ml/min. There was an inverse linear relationship between mean transit time and mean flow rate. All the effects of bisacodyl were fully or at least partially reversible. Volume and calculated radius of the test segment remained constant and did not change under bisacodyl. It is concluded, that the secretory effect of bisacodyl is mainly responsible for the decreased mean transit time rather than a direct effect on motility.

Effect of diphenolic laxatives on Na+-K+-activated ATPase and cyclic nucleotide content of rat colon mucosa in vivo.

1. The effect of bisacodyl and oxyphenisation on the Na+-K+- and Mg2+-activated ATPase and on the mucosa levels of cAMP and cGMP was investigated in transporting ligated loops of the rat colon in acute studies and in chronic feeding experiments 2. The specific activity of the Na+-K+-ATPase was lowered in both types of experiments, concomitantly with a reduction in net sodium absorption. The specific activity of the Mg2+-activated ATPase was unaffected. 3. The cAMP content per mg protein was elevated and the cGMP content decreased in the acute experiments in which the effect on transport was most marked. The content of cyclic nucleotides returned to normal within 2 h whereas absorption, Na+-K+-ATPase specific activity and the mucosal potential difference were still significantly depressed at that time. In chronic experiments with bisacodyl, cAMP was not affected and cGMP was increased in colon loops exhibiting reduced absorption. 4. The results indicate that the inhibition of the Na+-K+-activated ATPase by diphenolic laxatives may play a role in the inhibition of intestinal fluid absorption caused by these compounds. The increase of cAMP in acute experiments could point to a cAMP-mediated stimulation of secretory processes under this condition.

Inhibition of stimulated fluid secretion in the rat small and large intestine by opiate agonists

1. The influence of morphine, levorphanol, dextrorphan, loperamide and naloxone on the increase in intestinal fluid volume (IFV) caused by PGE1, vasoactive intestinal peptide (VIP), carbachol and bethanechol was investigated in the small intestine of rats. 2. Morphine reduced the basal IFV and the increase in IFV caused by PGE1, VIP and carbachol. The effect of bethanechol was not altered by morphine. 3. The effects of levorphanol were comparable to those of morphine, whereas dextrorphan was inactive. 4. Loperamide reduced the increase in IFV caused by PGE1, but not that caused by carbachol. 5. Naloxone enhanced the effect of PGE1 and VIP on IFV but neither altered basal IFV nor the effect of carbachol. This result may suggest an inhibitory influence of intestinal enkephalins on PGE1-or VIP-induced intestinal secretion. 6. The influence of opiates was further tested on the effect of the diphenolic laxative, bisacodyl and of the osmotic laxative, mannitol on water net flux in the tied off colon of the rat in situ. Morphine, levorphanol and loperamide reduced the effect of bisacodyl, whereas the effect of mannitol and the net water absorption in controls remained unchanged. 7. The experiments show an antisecretory effect of opiates on different types of stimulation of fluid secretion in the small and large intestine. It is concluded that the antidiarrhoeal action of opiates can be better explained by antisecretory than by smooth muscle action on the gut.

Effect of Bisacodyl on the Structure and Function of Rodent and Human Intestine

The effect of bisacodyl on intestinal structure and function was investigated. Net water transport was measured under steady state conditions in vivo during single pass infusions of rodent and of human intestinal segments. Each segment served as its own control. Bisacodyl inhibited water absorption in rat jejunum, ileum, and colon. The degree of inhibition was linearly related to the logarithm of the bisacodyl concentration over the range of 0.05 to 2.0 mg per 100 ml. In human jejunal segments, bisacodyl, 1 mg per 100 ml, caused net water secretion. Bisacodyl, 5 mg every 6 hr, increased ileostomy output by 15% when it was fed to 5 patients with established ileostomies. By light microscopy, bisacodyl, 2 mg per 100 ml, erased cytoplasmic and nuclear detail within surface absorptive cells of rat intestine. By electron microscopy, the involved cells contained sparse and abnormal cytoplasmic organelles and nuclei which were deficient in chromatin. These results suggest that the laxative effect of bisacodyl is related to its ability to inhibit intestinal water absorption. Reduced absorption may be secondary to changes in surface absorptive cells.