Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide.
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PMID:Diabetic gastroparesis. A critical reappraisal of new treatment strategies. 128 Oct 70

The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3 antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18-70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P less than 0.0005). Transit times through the left colon (P less than 0.0005) and rectosigmoid (P less than 0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P less than 0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. 213 32

To determine if carbohydrates perfused into the ileum affect gastric emptying and circulating levels of gastrointestinal hormones, 18 healthy subjects were intubated with an oroileal tube. A 400-cal (60% carbohydrate, 20% protein, 20% fat) homogenized meal labeled with 111In-DTPA was then infused into the stomach over 10 min. Simultaneously, a test solution of normal saline (n = 6) or 12.5 (n = 4), 25 (n = 4), 50 (n = 2), or 100 (n = 2) mg/min of carbohydrates (75% rice starch, 25% glucose) containing a nonabsorbable marker, polyethylene glycol, was continuously perfused into the terminal ileum at 3 ml/min for 7 h. In one-half of the subjects the perfusate contained an amylase inhibitor (3.3 mg/ml) that reduced starch digestion and carbohydrate absorption. Gastric emptying was measured by a dual-headed gamma-camera. Plasma concentrations of hormones and the amount of carbohydrates passing the ileum were measured every 10 min. The amylase inhibitor significantly reduced the absorption of complex carbohydrates from the terminal ileum (p less than 0.05). Gastric emptying was significantly slowed by ileal perfusion of carbohydrates (p less than 0.01). This effect was enhanced by the amylase inhibitor (p = 0.06). Plasma concentrations of C-peptide, glucagon, motilin, gastrin, and human pancreatic polypeptide were not related to gastric emptying or ileal perfusates, but decreased concentrations of gastric inhibitory polypeptide and neurotensin and increased concentrations of peptide YY were significantly associated (p less than 0.05) with slowing of gastric emptying. Perfusing carbohydrates into the ileum was associated with nausea, abdominal pain, and vomiting, but we could detect no direct relationship between the onset of these symptoms and gastric emptying. Slowing of gastric emptying of a homogenized mixed meal by the entry of complex carbohydrates into the ileum may be partly mediated by peptide YY or nonvagally mediated neural mechanisms.
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PMID:Effect of ileal perfusion of carbohydrates and amylase inhibitor on gastrointestinal hormones and emptying. 246 4

In the first part of this study, we compared the effects of morphine and trimebutine, two opioid receptor agonists, on small intestinal motility and plasma motilin in dogs. Morphine (100 micrograms/kg iv for 10 min) induced first a typical vomiting myoelectric profile followed subsequently by a migrating electrical activity mimicking phase III of the migrating myoelectric complex; trimebutine (5 mg/kg iv for 10 min) initiated only a migrating phase III-like activity. Despite their different initial contractile effects, both agents induced a significant and similar rise in plasma motilin that preceded the beginning of the premature phase III. In the second portion of the study, naloxone, an opioid receptor antagonist, was infused to verify the influence of endogenous opiates on plasma motilin and on the migrating motor complex. Naloxone (2 mg/kg, then 0.5 mg.kg-1.h-1 iv) delayed significantly the cyclic recurrence of plasma motilin peak increases and of the phase IIIs. In some animals, where naloxone abolished the phase IIIs, the amplitude of the motilin peak increases was significantly diminished. These results suggest 1) that opioid administration increases plasma levels of motilin by a mechanism that is independent of the intestinal contractile activity, and 2) that endogenous opioids could be physiological inducers of plasma motilin increases in the conscious dog.
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PMID:Regulation of plasma motilin by opioids in the dog. 254 42

The effect of cisplatin on interdigestive myoelectric activity (IDMA) of the gastric antrum, duodenum and jejunum, plasma concentration of motilin, and animal behavior was studied in seven conscious dogs with gastric cannulas and platinum electrodes implanted on the serosal surface of antrum and upper small intestine. Cisplatin given intravenously in a dose of 2 mg/kg resulted in complete interruption of IDMA and produced predominantly phase II-like activity, lasting as long as 24 hr. Six of the seven dogs exhibited retropropagation of spike bursts from the jejunum to the antrum which was accompanied by emesis. Retropropagation of spike bursts did not occur in one dog who did not exhibit emesis. In addition, abnormal spike bursts occurred frequently, including simultaneously occurring spike bursts in both duodenum and jejunum and nonpropagating short spike bursts in isolated segments of the upper small intestine. As phase III of IDMA disappeared, plasma motilin concentrations remained comparable to those in phase II of normal IDMA but without the cyclic increases. These studies indicate that cisplatin interrupts the regular cycle of IDMA as well as the plasma motilin cycle and produces retropropagation of spike bursts and abnormal spike bursts. These changes in both motility and plasma motilin levels may play a part in the mechanism of emesis induced by cisplatin in dogs.
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PMID:Effect of cisplatin on myoelectric activity of the stomach and small intestine in dogs. 334 26

This study evaluated the effect of gastric bypass on the glucose, insulin, vasoactive intestinal peptide (VIP), neurotensin, and motilin response to orally administered glucose in eight morbidly obese patients before and after operation. Preoperatively, all eight patients remained asymptomatic during an oral glucose tolerance test, which showed glucose intolerance and hyperinsulinism. Plasma VIP, neurotensin, and motilin remained below detectable levels for the entire test. At three months following gastric bypass (21% weight loss), all eight patients became acutely ill during a repeated oral glucose tolerance test and had the following symptoms: facial flushing (eight patients), palpitations (eight patients), nausea (seven patients), abdominal fullness (seven patients), pallor (four patients), diaphoresis (two patients), vomiting (two patients), and diarrhea (two patients). Significant release of neurotensin occurred in seven patients while three patients had release of VIP, further implicating these two peptides as part of the pathophysiologic spectrum of the "dumping syndrome."
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PMID:Neurotensin, vasoactive intestinal peptide, and Roux-en-Y gastrojejunostomy. Their role in the dumping syndrome. 398

Pathologic gastroesophageal reflux encountered during the neonatal period can be associated with projectile vomiting often of bile stained gastric content. Between 1960 and 1979, symptomatic gastroesophageal reflux was diagnosed in 36 neonates. Duodenogastroesophageal reflux was present in 16 or 44.4% of this group. This abnormal phenomenon is classically encountered in our experience during the neonatal period. The in-series incompetence of the pyloric and lower esophageal sphincteric mechanisms gives rise to a variant of the so called phreno-pyloric syndrome. The seriousness of this association is emphasized in our series by the high incidence of complications encountered in the patients with this syndrome, i.e., gastroesophageal bleeding in 44% esophagitis with stricture of formation in 12.5%. Conservative management of the cases encountered with this syndrome was successful except in two cases where reflux esophagitis was complicated by severe stricture formation. It is postulated that the pathogenesis of this form of phreno-pyloric syndrome is most probably based upon a motility disturbance of the upper gastrointestinal tract, involving the hormone motilin.
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PMID:The phreno-pyloric syndrome in symptomatic gastroesophageal reflux. 707 96

Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.
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PMID:Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs. 760 Apr 51

The effects of octreotide on six normal subjects and five patients with scleroderma were investigated. Changes in intestinal motility and in plasma motilin were examined after a single injection of octreotide. Octreotide stimulated intense intestinal motor activity in normal subjects. Motility patterns in the scleroderma patients were chaotic and non-propagative, but, after octreotide was given, became well coordinated, aborally directed, and nearly as intense as in normal volunteers. Clinical responses and changes in breath hydrogen were also evaluated in the five scleroderma patients who had further treatment with octreotide at a dose of 50 micrograms/day subcutaneously for three weeks. A reduction in symptoms of abdominal pain, nausea, vomiting, and bloating was seen. Additionally, there was an improvement in bacterial overgrowth as objectively measured by breath hydrogen testing. The effects of octreotide (100 micrograms/day subcutaneously) on the perception of rectal distension were investigated in a double blind, placebo controlled study in healthy volunteers. Octreotide was shown to reduce the perception of rectal distension without affecting motor pathways or local rectal reflexes. This enhanced tolerance to volume distension seems to result from inhibition of sensory afferent pathways as shown by electroencephalographic studies showing diminished evoked spinal and cortical potentials after octreotide. In irritable bowel syndrome patients with rectal urgency, octreotide reduces rectal pressures and perception after rectal distension to near normal values.
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PMID:Octreotide in gastrointestinal motility disorders. 820 95

Nausea and vomiting are debilitating symptoms complicating many clinical conditions. Conventional antiemetic agents act as muscarinic, histamine, and dopamine receptor antagonists in the central nervous system. In a retrospective analysis, tricyclic antidepressant drugs demonstrated efficacy in long-term treatment of functional nausea. Some cases of vomiting result from impaired gastrointestinal motor activity. Agents which act on gastric serotonin (5-HT4), dopamine, and motilin receptors accelerate gastric emptying and relieve symptoms in gastroparesis. Recent investigations suggest that some patients with refractory gastroparesis may benefit from gastric electrical pacing. The treatment of acute chemotherapy-induced emesis was revolutionized by 5-HT3 receptor antagonists; however, these agents are less efficacious in delayed vomiting. Neurokinin (NK-1) receptor antagonists show promise in treating delayed chemotherapy-evoked emesis. Furthermore, animal studies indicate a broad spectrum of action for NK-1 antagonists in treating diverse causes of nausea and vomiting. The cyclic vomiting syndrome is characterized by discrete episodes of relentless vomiting separated by asymptomatic intervals and is associated with migraine headaches. Antimigraine therapies including the 5-HT1D receptor agonists sumatriptan reduce the severity of cyclic vomiting attacks. Investigations into these and other novel treatments may provide important advances in the care of difficult cases of nausea and vomiting resulting from disparate illnesses.
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PMID:Novel approaches to the treatment of nausea and vomiting. 1069 61


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