Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 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 effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.
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PMID:Gastrointestinal motor effects of erythromycin in humans. 195 15

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

Antagonists of 5-hydroxytryptamine type 3 (5HT3) receptors reduce the nausea induced by cisplatinum, but the effects of these agents on 5HT3 receptors in the human gut remain to be defined. We examined the actions of one of these drugs (Glaxo GR 38032F) on small intestinal transit and mouth-to-cecum transit times in healthy man. We also quantified its effects on the release of peptide YY (PYY), neurotensin, human pancreatic polypeptide, gastrin-cholecystokinin, and motilin. Ten healthy volunteers were enrolled in a randomized, double-blind, placebo-controlled crossover study. Following a single intravenous dose of GR 38032F (0.15 mg/kg), we measured the time to appearance in plasma of sulfapyridine after injection of salicylazosulfapyridine into the duodenum. This was used as a measure of duodenocecal transit. The appearance of hydrogen in breath after ingestion of a meal containing lactulose was also correspondingly used to quantify the mouth-to-cecum transit of the "head" of the meal. Gastrointestinal hormones were assayed in plasma by specific RIAs; samples were drawn fasting (10 min after injection) and after breakfast (358 calories: 15.7 g protein, 55.4 g carbohydrate, 8.1 g fat). The postprandial integrated response and peak release of PYY was decreased by GR 38032F. There was also a trend for the peak release of neurotensin to be reduced. GR 38032F did not significantly alter small intestinal transit times or mouth-to-cecum transit times. We conclude that GR 38032F does not have a major effect on small intestinal transit in health.
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PMID:Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides. 252 8

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

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

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.
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PMID:Safety, toleration, and pharmacokinetics of intravenous azithromycin. 891 68

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

Our aim was to investigate the effect of motilin on postprandial proximal gastric motor and sensory function in healthy volunteers. Ten fasted, healthy volunteers were infused intravenously with synthetic motilin or placebo over 90 min. A liquid meal (200 ml) was ingested within 2 min at the start of the infusion. Proximal gastric volume was measured with a barostat device. Abdominal symptoms were scored by visual analog scales. Plasma motilin concentrations were measured using RIA. Endogenous motilin levels were not affected by meal ingestion. After meal intake, gastric relaxation was similar for motilin and placebo. After postprandial relaxation, motilin resulted in a faster return of gastric volume to baseline (P = 0.007). Motilin significantly increased postprandial feelings of nausea (P = 0.03) and tended to increase abdominal pain and abdominal tension. In conclusion, after normal postprandial gastric relaxation, motilin accelerated the return of gastric volume to baseline. In addition, motilin increased postprandial feelings of nausea.
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PMID:Exogenous motilin affects postprandial proximal gastric motor function and visceral sensation. 1218 23


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