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)

The usefulness of xanthine bronchodilators in the treatment of asthma is often limited by the side effects of nausea and vomiting. We investigated the mechanism of emesis induced by xanthines, by examining the roles of phosphodiesterase (PDE) inhibition and adenosine antagonism. Theophylline, enprofylline, 8-phenyltheophylline and isobutylmethylxanthine (IBMX), as well as vehicle, were given to ferrets at doses ranging from 0.1 to 150 mg/kg i.p. The potencies of these compounds in producing emetic responses were ranked IBMX greater than enprofylline greater than theophylline greater than 8-phenyltheophylline. These results correlate well with the relative potencies of the compounds as nonselective PDE inhibitors but do not correlate with their relative potencies as adenosine A1 or A2 receptor antagonists. The emetic responses also correlate well with the previously reported potencies of these xanthines as bronchodilators in guinea pigs. We conclude that the emetic side effect of xanthine bronchodilators results from the inhibition of one or more forms of PDE rather than from adenosine antagonism.
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PMID:Mechanism for the emetic side effect of xanthine bronchodilators. 168 99

We compared the efficacy and safety of ondansetron (GR 38032F), a selective antagonist of serotonin S3 receptors, with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer. The patients received either three intravenous doses of ondansetron (0.15 mg per kilogram of body weight) or normal saline (placebo) at four-hour intervals, beginning 30 minutes before the administration of cisplatin. Nausea and vomiting were markedly diminished in the group given ondansetron. The median time to the first episode of emesis was 2.8 hours in the placebo group and 11.6 hours in the ondansetron group (P less than 0.001); the median number of episodes in 24 hours was 5.5 in the placebo group and 1.5 in the ondansetron group (P less than 0.001); the mean (+/- SEM) number of regurgitations or dry heaves per episode was 3.2 +/- 0.5 in the placebo group and 1.17 +/- 0.1 in the ondansetron group (P less than 0.001). None of the 14 patients given ondansetron, but 12 of 14 given placebo, required treatment with antiemetic-rescue agents for the control of nausea and vomiting. There were no adverse effects attributable to ondansetron. The urinary excretion of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, was increased in all patients two to six hours after they received cisplatin chemotherapy, and the increases paralleled the episodes of emesis. We conclude that ondansetron is an effective and safe agent for controlling the nausea and vomiting induced by cisplatin treatment. We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells, and that ondansetron acts by blocking S3 receptors for serotonin.
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PMID:Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. 214 2

Many chemotherapeutic agents have been evaluated during the last 40 years and some have now an established place in the management of malignant disease. However these agents have a level of toxicity well above any other group of drugs. Chemotherapeutic agents do not discriminate between normal and neoplastic tissue. Chemotherapeutic regimens that are toxic to rapidly dividing malignant cells, are liable to be particularly harmful to lymphoid tissues, bone marrow and the epithelium of the gastrointestinal tract. The side effects due to chemotherapy are classified as immediate, early, delayed and late. Immediate side effects are those that may occur within the first 24 hours of treatment. The most common immediate side effect is nausea and vomiting, due to direct central effect on the vomiting center of the brain. Cisplatin and nitrogen mustard are particularly prone to this complication. The antiemetics usually used are metoclopramide, domperidone and steroid. The efficacies of these drugs are not so good for nausea and vomiting due to cisplatin administration, however several blockades against serotonin M-receptor recently developed are quite effective to nausea and vomiting of chemotherapeutic regimens including cisplatin. Early side effects commence within about one month of therapy. The most common is bone marrow toxicity and can occur after therapy with the vast majority of anticancer drugs. The relative importance of leukopenia and thrombocytopenia vary between the drugs and their route of administration. Recently, hematopoietic cytokines, such as granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSP) have been introduced to granulocytopenia developed by cancer chemotherapy. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy and marked efficacy on infection in granulocytopenic patients were observed. In addition to this, autologous bone marrow transplantation after chemotherapy has been described in patients with solid tumors.
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PMID:[Palliative therapy in cancer. 5. Side effects by anticancer drugs and their treatments]. 169 55

This report is a prospective study of 223 patients with intractable cancer pain who were offered continuing care during the year 1988 at the Pain Relief Unit, Kidwai Memorial Institute of Oncology, Bangalore, India, with a minimum follow-up of 4 months and a maximum follow-up of 16 months. A high percentage of pain relief was attained within a mean duration of 4 days, which on follow-up was maintained at a steady level in most patients (91.1%). Oral morphine could not be continued in three patients because of vomiting. The main side effects noticed were nausea and vomiting, itching, and constipation. At any time during the first 140 days, only 30% of patients had side effects and appropriate medication successfully managed these side effects. During the rest of the study period, the side effects were minimal. Oral morphine used with proper adjuncts offers the best pain palliation in most patients, with minimal side effects.
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PMID:Continuing care for cancer pain relief with oral morphine solution. One-year experience in a regional cancer center. 169 28

Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the 'moderate' doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics.
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PMID:Ondansetron. Therapeutic use as an antiemetic. 171 61

Granisetron (BRL 43694) is a highly selective 5-HT3 receptor antagonist which possesses significant antiemetic activity, likely mediated through antagonism of 5-HT3 receptors on abdominal vagal afferents and possibly in or near the chemoreceptor trigger zone. Clinical trials in cancer patients demonstrate that, compared with placebo, granisetron significantly reduces the incidence of nausea and vomiting for 24 hours after administration of high-dose cisplatin. In large comparative trials, 70% of patients who received granisetron prior to cisplatin or other chemotherapy experienced complete inhibition of vomiting with little or no nausea for 24 hours after antineoplastic administration; these results were similar to those obtained with high-dose metoclopramide plus dexamethasone, and superior to a combination of chlorpromazine plus dexamethasone, or prochlorperazine plus dexamethasone, or methylprednisolone monotherapy. The most frequently reported adverse event associated with granisetron administration is headache which occurs in about 10 to 15% of patients while constipation, somnolence, diarrhoea and minor transient changes in blood pressure have been reported less frequently. Extrapyramidal effects, which can occur with high-dose metoclopramide and may be a limiting factor in its use, have not been noted with granisetron administration. Thus, granisetron is an effective, well tolerated and easily administered agent for the prophylaxis of nausea and vomiting induced by cancer chemotherapy which appears to be devoid of extrapyramidal side effects associated with metoclopramide. As a member of a new class of drugs, the selective 5-HT3 receptor antagonists, granisetron provides the medical oncologist with a new, potentially more acceptable antiemetic therapy.
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PMID:Granisetron. A review of its pharmacological properties and therapeutic use as an antiemetic. 172 76

he safety and efficacy of oral transmucosal fentanyl citrate (OTFC) as a preanesthetic medication and the efficacy of droperidol as a prophylactic anti-emetic were evaluated in 100 children aged 2-8 yr undergoing general anesthesia for outpatient surgery. Patients were randomly assigned to one of four groups and managed in a double-blinded manner: 1) placebo lozenge 45 min preoperatively and placebo (normal saline) injected intravenously after induction of anesthesia; 2) placebo lozenge 45 min preoperatively and 50 micrograms/kg droperidol intravenously after induction; 3) 15-20 micrograms/kg OTFC lozenge 45 min preoperatively and placebo intravenously after induction; and 4) 15-20 micrograms/kg OTFC lozenge 45 min preoperatively and droperidol 50 micrograms/kg intravenously after induction. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Heart rate, respiratory rate, blood pressure, and hemoglobin oxygen saturation (SpO2) were monitored throughout the study. Scoring systems were used to evaluate sedation, anxiety, cooperation, and ease and quality of anesthetic induction. Emergence, recovery, and discharge times were recorded. Nausea, vomiting, and adverse effects were noted. Preoperatively, children receiving OTFC had significantly greater sedation, slower respiratory rates, lower SpO2, and less excitement during induction. Postoperative nausea and vomiting occurred significantly more frequently after OTFC than after placebo. Prophylactic droperidol did not significantly reduce the incidence of nausea and vomiting. The authors conclude that, in pediatric surgical outpatients, OTFC reliably induces preoperative sedation and facilitates inhalation induction of anesthesia, but it is associated with significant decreases in respiratory rate and SpO2 and a high incidence of postoperative nausea and vomiting that is not significantly reduced by prophylactic droperidol.
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PMID:Oral transmucosal fentanyl citrate for preanesthetic medication of pediatric day surgery patients with and without droperidol as a prophylactic anti-emetic. 172 35

The effects on gastric and duodenal mucosa induced by cisplatin plus etoposide (PE) chemotherapy were investigated in 32 patients with lung cancer. They were submitted to gastroduodenoscopy before receiving cisplatin 100 mg/m2 (day 1) plus etoposide at a mean dose of 107 mg/m2 (days 1, 3 and 5). Endoscopic examination was repeated on day 8. Before chemotherapy, 22 patients showed normal endoscopic appearance and 10 minimal lesions (3 or fewer erosions). After chemotherapy, 16 remained normal, 1 had minimal lesions and 15 developed major lesions: 11 gastric or duodenal multiple erosions, 1 diffuse erosive gastritis, 2 gastric and 1 duodenal ulcer (p less than 0.001). No difference was observed in the number of vomiting episodes nor in severity of upper gastrointestinal symptoms between the patients who remained normal and those who developed mucosal injury. We conclude that PE chemotherapy can have a properly called gastroduodenal toxicity, leaving nausea and vomiting out which are rather due to central than peripheral mechanisms. Some trials are necessary to investigate which kind of drugs (H2-receptor blockers, sucralfate, prostaglandin E analogues) may be useful in preventing acute gastroduodenal mucosal injury induced by PE chemotherapy.
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PMID:Acute gastroduodenal mucosal injury after cisplatin plus etoposide chemotherapy. Clinical and endoscopic study. 174 80

Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3-6 mg.kg-1.d-1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy.
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PMID:Controlling cancer chemotherapy-induced emesis. An update. 174 7

Nausea and vomiting are frequent side-effects of intravenous cancer chemotherapy. How these complications were related to the gastric mucosal function was investigated by measuring the gastric mucosal potential difference (PD). Eight patients with metastatic breast cancer receiving chemotherapy were investigated. The liquid junction-corrected gastric PD and pH were measured with a newly developed microelectrode. The measurements started half an hour before chemotherapy and continued for 4-5 hours. Nausea, vomiting, psychological stress and sleeping episodes were registered. The initial PD values were -34 mV +/- 8 mV (mean +/- SD). During the observation period 6 of 8 patients had one or more episodes of nausea and vomiting. All episodes were preceded by a significant decline in PD. The magnitude of the decline in PD was unrelated to the time-lag between administration of chemotherapy and the occurrence of nausea and vomiting, and there was no correlation between the time for these episodes and the time for the administration of the chemotherapy. One patient had three episodes of severe psychological stress causing a marked decline in PD. The last patient experienced no nausea, vomiting or stress and had no changes in PD. During sleeping periods PD increased significantly.
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PMID:Changes in the gastric potential difference during chemotherapy in patients with metastatic breast cancer. 176 71


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