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PubMed1994

Drug interactions with antacids. Mechanisms and clinical significance.

Concomitant use of antacid preparations with other medications is common. The potential for antacid-drug interactions is dependent upon the chemistry and physical properties of the antacid preparation. The intragastric release of free aluminum and magnesium ions has potent effects on gastrointestinal function and on drug pharmacokinetics. Antacid-drug interactions may occur secondary to changes in gastrointestinal motility or alterations in gastric and urinary pH. Direct adsorption also results in decreased drug bioavailability. Human drug interaction studies are usually performed with healthy volunteers; extrapolation of these results to clinical situations may not always be valid. However, the current literature would suggest that significant interactions with antacids do occur with certain members of the quinolone, nonsteroidal anti-inflammatory drug (NSAID) and cephalosporin classes of drugs. Notable interactions also occur with tetracycline, quinidine, ketoconazole and oral glucocorticoids. These interactions are particularly relevant in the patient with sepsis, cardiac disease or inflammatory syndromes.

Administration, Oral↗
PubMed1999

In-utero defecation: fact or fiction?

An experimental study was performed to investigate the gastrointestinal motility and in-utero defecation by radionuclide techniques. Forty-eight New-Zealand white rabbit fetuses at 25 days' gestation (fullterm, 31 to 32 days) were divided into two groups as A (n: 24) and B (n: 24). 0.1 ml of Technetium-99m (99mTC)-HIDA (a derivative of iminodiacetic acid) containing 1 mCi of radioactivity was injected into the gluteus muscle of each fetus, which had been exposed through the uterus. This procedure was used for all fetuses and additionally surgical closure of anus by a purse string suture was performed in Group B fetuses. After replacing the fetus and uterus into the abdomen, and beginning 1 hour after injection, a live fetus was killed each hour for 24 hours. Tissue samples from the reference organs (lung, heart, stomach, kidney, bladder), liver, meconium in the proximal, mid and distal bowel, and amniotic fluid were taken. The radioactivity of each sample was determined by a gamma counter and the percentage injected dose (uptake) per gram of tissue is calculated. 99mTc-HIDA was predominantly trapped by the liver via systemic circulation and excreted into the gastrointestinal tract in both groups through which it passed into the amniotic fluid only in Group A. The very low radioactivity levels detected in the amniotic fluid of Group B originated from urinary tract and indicated the in-vivo stability of 99mTc-HIDA, thus reliability of the experimental model. Intestinal transport of a radiopharmaceutical agent in both groups and demonstrated passage into the amniotic fluid only in Group A strongly suggest that fetal defecation is a physiologic event.

Amniotic Fluid↗
PubMed2000

New developments in the treatment of irritable bowel syndrome.

The irritable bowel syndrome (IBS) is one of the most common gastrointestinal conditions encountered by general practitioners, and it accounts for a great deal of the workload of gastroenterologists in secondary care. Research to date indicates that several factors contribute to the development of IBS, of which disturbed gastrointestinal motility, altered visceral perception and psychosocial factors are regarded as the three most important mechanisms interacting in the development of this disorder. Most pharmacological research has been based on these insights. Several agents capable of modulating either motility or sensitivity are currently under investigation. Potential drugs in the treatment of diarrhoea-predominant IBS are the more selective antispasmodics, such as the M3-receptor antagonists (e.g. zamifenacin, darifenacin). In constipation-predominant IBS the colokinetic effects of the selective 5HT4 agonists prucalopride and tegaserod are of great interest. Since altered visceral perception is thought to play an important role in the genesis of abdominal pain and bloating in many patients with IBS, new drugs are targeted at modulating the sensitivity, such as 5HT3 antagonists (e.g. alosetron), kappa-agonists (e.g. fedotozine) and somatostatin analogues. Furthermore, psychosocial factors should not be overlooked, since these appear to be of great influence on the clinical outcome of IBS.

Colonic Diseases, Functional↗
PubMed1999

Myenteric neuronal antibodies in scleroderma: passive transfer evokes alterations in intestinal myoelectric activity in a rat model.

Although the mechanism for neuropathic gastrointestinal motility disturbances in scleroderma is unknown, we have previously described anti-myenteric antibodies in some patients with scleroderma. The aim of this study was to screen patients with scleroderma who had gastrointestinal symptoms for the presence of anti-myenteric neuronal antibodies and then purify the immunoglobulin G (IgG) fraction from serum samples for passive immunization into a rat model and observe for intestinal motility effects. Patients with scleroderma were screened, a serum sample from a patient with high titer anti-myenteric neuronal antibodies was obtained, and IgG was purified. Using a rat model with chronic indwelling intestinal electrodes to measure intestinal myoelectric activity, we passively transferred the IgG from either control subjects or this patient with scleroderma. We immunosuppressed the rats and intraperitoneally injected IgG from control subjects and this patient with scleroderma daily for 7 days. Recordings of myoelectric activity in control injected rats revealed no difference from baseline, but a prolongation in the activity front duration and interval and a disruption were seen after scleroderma IgG injections. IgG from a patient with scleroderma with antimyenteric neuronal antibodies, when passively immunized into a rat model, evokes intestinal myoelectric activity alterations. We hypothesize that these antibodies could account for the gastrointestinal neuropathic motility disturbances seen in scleroderma.

Animals↗
PubMed2006

The use of electrogastrography and external ultrasonography to evaluate gastric motility in Crohn's disease.

Although Crohn's disease is associated with various digestive symptoms, there have been few reports on gastric motility. In this study, we conducted a study of gastric motility in Crohn's disease using 20 healthy subjects (N group) and 15 patients with Crohn's disease (C group) by electrogastrography (EGG) using a Nipro electrogastrograph. An EGG was recorded for 30 minutes in a fasting state and after ingestion of 300 ml of a liquid meal. As an index of gastric emptying, the rate of change in the cross-sectional area of the gastric antrum was measured 1 and 15 minutes after ingestion of the liquid meal by external ultrasonography. In an EGG frequency analysis, waveforms with a peak of 3 cycles/minute (cpm) were noted in the N group, and the peak amplitude increased significantly after the ingestion of food. In the C group, division of the normal-gastria component was noted after the ingestion of food in 5 patients (33.3%). In a comparison of the peak amplitudes of fasting brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitude was significantly increased in normal-gastria in the N group, and in brady-gastria and tachy-gastria in the C group. In a comparison of the rates of food ingestion-induced changes in the peak amplitudes for brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitudes were significantly increased in normal-gastria in the N group, but not in the C group. In the case of gastric emptying investigated by external ultrasonography, the rate of food ingestion-induced change in the cross-sectional antrum area was significantly lower in the C group (50.5+/-9.2%) than in the N group (65.0+/-8.5%). For gastrointestinal motility, a 3 cpm normal-gastria represents efficient gastric motility. In the C group, the peak amplitudes of brady-gastria and tachy-gastria were significantly increased, but were low in normal-gastria in the fasting EGG, postprandial division of the normal-gastria component was noted, and the rate of food ingestion-induced increase in the normal-gastria peak amplitude was significantly lower than that in the N group, suggesting that patients with Crohn's disease have a functional abnormality in, not only the small and large intestine, but also the stomach.

Adult↗
PubMed2005

Muscarinic and 5-HT4 receptors participate in the regulation of the frequency of spontaneous contractions of the longitudinal muscle in rat distal colon.

Spontaneous contractions of the intestine are thought to play an important role in the gastrointestinal motility, including peristalsis. In the present study, we investigated mechanisms for regulation of the frequency of spontaneous contractions, using longitudinal muscle strips in rat distal colon. Atropine significantly decreased the frequency of spontaneous contractions, indicating that neuromuscular transmission via muscarinic receptors increases the frequency of spontaneous contractions. SB-204070, 5-HT4 receptor antagonist also significantly decreased the frequency of spontaneous contractions, indicating that the activation of 5-HT4 receptors also increases the frequency of spontaneous contractions. In conclusion, it is suggested that muscarinic and 5-HT4 receptors participate in the regulation of the frequency of spontaneous contractions in the longitudinal muscle in rat distal colon, and that the frequency of spontaneous contraction is controlled by the enteric neurons.

Animals↗
PubMed1996

Gastrointestinal recovery following laparoscopic vs open colon surgery.

BACKGROUND: We prospectively studied the recovery of gastrointestinal motility in patients undergoing laparoscopic (LAP, n = 7) or open (OPEN, n = 7) colon resections. METHODS: At operation, bipolar recording electrodes were placed on the proximal and distal antrum, the proximal site of the colonic anastomosis, and the rectosigmoid for postoperative myoelectric recordings. RESULTS: Shorter postoperative hospitalization and earlier resumption of a regular diet of the LAP group just barely failed to achieve significant differences when compared with the OPEN group (p = 0.091, p = 0.050, respectively). There were no differences between groups for slow wave frequency, amplitude, or dysrhythmias in the antrum, nor for return of discrete (DERA) and continuous (CERA) electrical response activity in the colon. Percentage of slow waves with spike activity tended to increase with passage of time postoperatively in both groups. There was a significant difference between POD 3 and 7+ in the LAP group (p < 0.05). However, there were no significant differences in the percentage of slow waves with spike activities between groups on any postoperative day. CONCLUSIONS: The potential benefits of using a laparoscopic approach to colon resection are not clearly confirmed by these data. While such an approach may possibly result in shorter hospitalization, it appears to offer at best only modest increases in the rapidity of recovery of gastrointestinal function.

Anastomosis, Surgical↗
PubMed1977

[The effect of caerulein on intraluminal pressures of the common bile duct and duodenum in man (author's transl)].

Caerulein is a dekapeptide related to gastrin and cholecystokinin with profound effects on gastrointestinal motility. In the present study we examined the effect of intravenously administered caerulein (0.1 microgram/kg body weight) on the intraluminal pressure of common bile duct and duodenum in 12 patients. The pressure recordings were obtained by endoscopic perfusion manometry. The tip of the perfused catheter was positioned under radiological control and the measurements were carried out under standardized conditions. Following the injection of caerulein there was a rise in pressure in the common bile duct and the mid portion of the duodenum. The pressure increase in the common duct appears to be predominantly due to contraction of the gallbladder as it is considerably less pronounced in patients with cholecystectomy. The problems inherent to endoscopic pressure recordings under pharmacological stimulation are discussed.

Adult↗
PubMed2006

The spontaneously diabetic Torii rat with gastroenteropathy.

The spontaneously diabetic Torii (SDT) rat was recently recognized as a new animal model of non-obese type 2 diabetes. As the severe diabetic ocular complications seen in SDT rats already have been investigated, we examined another common diabetic complication, gastroenteropathy. Male SDT rats developed diabetes at 20 weeks and diarrhea at 28 weeks of age. Gastrointestinal motility was evaluated at 28 weeks by measuring the distance of small intestinal transit by oral administration of the non-absorbed marker, arabic gum. SDT rats exhibited greater intestinal transit distance than control SD rats (54.1+/-2.6% versus 43.0+/-1.2%). Insulin treatment of SDT rats begun at 20 weeks of age produced improved stool and reduced intestinal transit distance (41.4+/-0.3%). Morphologically, the SDT rats exhibited longer villi and heavier weight of intestine compared to control SD rats. These results suggest that the SDT rat may be a useful animal model for studies of diabetic gastroenteropathy.

Animals↗
PubMed2002

KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats.

KDR-5169, 4-amino-5-chloro-N-[1-(3-fluoro-4-methoxybenzyl)piperidin-4-yl]-2-(2-hydroxyethoxy)benzamide hydrochloride dihydrate, is a new prokinetic with a dual action, i.e., stimulation of the 5-HT4 receptor and antagonism of the dopamine D2 receptor. In this study, we determined in vitro activities of KDR-5169 towards both receptors and demonstrated the effect of the compound on gastrointestinal motor activity in conscious dogs and rats. In dogs, intravenous KDR-5169 stimulated upper gastrointestinal motility in the fasting state and also eliminated the depressive effect of 3,4-dihydroxyphenylalanine (L-DOPA) on this motility in the postprandial state. The effect of KDR-5169 on gastric emptying was further characterized by the use of three rat gastroparesis models (dopamine D2 receptor agonist (quinpirol)-, abdominal surgery-, or combined-situation-induced). Domperidone (a dopamine D2 receptor antagonist) was effective in the quinpirol-delay and combination-delay models, and cisapride and mosapride (5-HT4 receptor agonists) were effective in the surgery-delay model. Only KDR-5169 eliminated the delay of gastric emptying in all three models. In addition, KDR-5169 accelerated emptying to above the normal level in the combination-delay model. These results suggest that KDR-5169 would be effective in various types of gastric ileus caused by different mechanisms.

Animals↗
PubMed2002

Understanding and controlling the enteric nervous system.

The enteric nervous system or the 'Little Brain' of the gut controls gastrointestinal motility and secretion, and is involved in visceral sensation. In this chapter, new developments in understanding the function of the enteric nervous system are described. In particular, the interaction of this system with the interstitial cells of Cajal, the pacemaker cells of the gut, is highlighted. The importance of the interaction between the enteric nervous system and the immune system is discussed, especially in relation to functional bowel disorders and post-operative ileus. Evidence is also provided that neurones can change their function and phenotype, a phenomenon called neuronal plasticity, which contributes to the pathogenesis of visceral hypersensitivity. Finally, new developments in stem cell transplantation are described. All these new insights should lead to a better understanding of the enteric nervous system and hopefully to better ways of controlling it.

Coiled Bodies↗
PubMed2003

New benzimidazole derivatives: selective and orally active 5-HT3 receptor antagonists.

The synthesis of new 5-HT(3) receptor antagonists is an interesting field of research because of their wide therapeutic use. The aim of this work is to functionally characterise a new series of benzimidazole derivatives previously described. These compounds bind to 5-HT(3) receptors and have been evaluated using in vitro (rat tunica muscularis mucosae) and in vivo tests (Bezold-Jarisch reflex in rat and gastrointestinal motility and spontaneous motility in mice). Ondansetron and 1-[4-amino-5-chloro-2-(3,5-dimethoxyphenil)methyloxy]-3-[1-[2-methylsulfonylamino]piperidin-4-yl]propan-1-one hydrochloride (RS 39604) were used as well known 5-HT(3) and 5-HT(4) receptor antagonists. These benzimidazole derivatives have proved to be 5-HT(3) receptor antagonists. Interestingly, they are as active as ondansetron when they are intraperitoneally (i.p.) or orally (p.o.) administered and, in mice, they seem to induce fewer behavioural changes at similar effective doses than does ondansetron. The present results confirm the usefulness of the previously proposed pharmacophore and justify the interest in these new benzimidazole derivatives.

5-Hydroxytryptophan↗
PubMedDate not supplied

[Influence of resting the digestive duct in gastric emptying. Comparison of 2 nutritional modalities: glucidic enteral and total parenteral nutrition].

Gastrointestinal motility is altered in several clinical situations in which Total Parenteral Nutrition (TPN) is indicated. Nevertheless, the effects of TPN on motility are not well known. In this study, Wistar rats (250-280 g) were divided into two groups were defined according to the route of administration of the nutrients: Group A (with TPN: 100% of the total non-protein calories administered as glucose), and Group B (solid enteral nutrition, but with the infusion of normal saline under the same conditions as in the previous group). Each group was subjected to three different infusion times: 24 hours, 3 days, and 5 days post-intervention, after which the gastric emptying was measured by means of the phenol red test. TPN delayed emptying in all the times with respect to group B, although significant differences were only found after 3 days of infusion.

Animals↗
PubMed1980

The effect of parathyroid hormone on the esophageal smooth muscle of the opossum.

The effect of parathyroid hormone on the gastrointestinal motility was studied in vitro. Isolated circular smooth muscle of the opossum esophagus were stimulated by electrical field stimulation in the absence and the presence of increasing concentration of PTH. The addition of 0.1-1.0 U./ml. of PTH to the bath resulted in 21-93% increases in the amplitude of the off response of the circular strips. Complete blockade of the neural transmission with tetrodotoxin abolished the effect of PTH. Atropine (10(-6) M) did not block the augmentatory effect of PTH on the off response. In conclusion, PTH has augmentatory effect on the off response of circulatory smooth muscle of the opossum esophagus. This effect is presumably related to the cryptogenic nerves responsible for the off response. The clinical significance of this effect is yet to be studied.

Animals↗
PubMedDate not supplied

PD 142676 (CI 1002), a novel anticholinesterase and muscarinic antagonist.

Inhibition of brain acetylcholinesterase (AChE) can provide relief from the cognitive loss associated with Alzheimer's disease (AD). However, unwanted peripheral side effects often limit the usefulness of the available anticholinesterases. Recently, we identified a dihydroquinazoline compound, PD 142676 (CI 1002) that is a potent anticholinesterase and a functional muscarinic antagonist at higher concentrations. Peripherally, PD 142676, unlike other anticholinesterases, inhibits gastrointestinal motility in rats, an effect consistent with its muscarinic antagonist properties. Centrally, the compound acts as a cholinomimetic. In rats, PD 142676 decreases core body temperature. It also increases neocortical arousal, as measured by quantitative electroencephalography, and cortical acetylcholine levels, measured by in vivo microdialysis. The compound improves the performance of C57/B10j mice in a water maze task and of aged rhesus monkeys in a delayed match-to-sample task involving short-term memory. The combined effect of AChE inhibition and muscarinic antagonism distinguishes PD 142676 from other anticholinesterases, and may be useful in treating the cognitive dysfunction of AD and produce fewer peripheral side effects.

Animals↗
PubMed1979

Inhibition of gastric acid secretion by a glycoprotein isolated from human urine (human urinary gastric inhibitor).

The gastric antisecretory activity of an inhibitor newly isolated from human urine (Human Urinary Gastric Inhibitor or HUGI) has been studied. HUGI was given intravenously and its activity determined in the following test systems: gastric secretion in the rat with pyloric ligation; gastric secretion in the dog with a Heidenhain pouch stimulated with pentagastrin, histamine and a protein meal; acid secretion by the isolated gastric mucosa of the rat; gastrointestinal motility; bile flow and gall-bladder tone and arterial and venous blood pressure and heart rate. HUGI was found to have marked activity only in the pyloric-ligated rats and in the dogs with Heidenhain pouches stimulated by a protein meal. Particularly in the dog, HUGI (0.1 to 6.4 micrograms/kg, i.v) markedly inhibited gastric secretion, dose-dependently and without changing the plasma gastrin concentration. Negative results were obtained in the other tests, but these results serve to demonstrate that HUGI is an inhibitor well-differentiated from other glycoproteins or peptides with gastric antisecretory activity, such as urogastrone and GIP. The results obtained to date are not sufficient to allow the mechanism of action of HUGI to be defined.

Animals↗
PubMed1978

The effect of crystal size, gastric content and emptying rate on the absorption of nitrofurantoin in healthy human volunteers.

The effect of four crystal sizes, gastric contents, and gastrointestinal motility on the absorption and excretion of nitrofurantoin was studied in three separate cross-over studies on 10 healthy volunteers. Microcrystal preparation gave an early and high serum peak. The greater the crystal size was, the smaller was the peak serum concentration. Correspondingly, microcrystal preparations gave initially very high nitrofurantoin concentrations in urine. Macrocrystal preparation had a not significantly longer excretion time than the other preparations. Food did not increase the serum nitrofurantoin concentrations, but excretion during 4 to 6 h was considerably greater than after fasting. In contrast, antacid and the use of a delayed-release preparation greatly worsened the biovailability of nitrofurantoin. An increased gastric emptying rate induced by metoclopramide significantly worsened the absorption of nitrofurantoin, but atropine only retarded the absorption and the principal excretion in urine occurred during 4 to 8 h.

Adult↗
PubMed2005

Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT(4) receptor agonists.

It is thought that selective 5-HT(4) receptor agonists-such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4ylmethyl]benzamide (2)-have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects. Modification of 2 was performed. Variation of the piperidin-4ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT(4) receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT(4) receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N-(piperidin-4ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT(4) receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT(4) receptor agonists, and had a similar effect on defecation to compound 2.

Animals↗