Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anticipatory nausea and vomiting (ANV) are learned responses to chemotherapy that develop in up to 25% of patients by the fourth treatment cycle. Post-treatment nausea and emesis must occur before development of ANV can take place. Certain patient characteristics and other responses to chemotherapy can also be used to predict their occurrence. Once they develop, ANV cannot be controlled by pharmacologic means including use of new 5-HT3 receptor antagonists. By contrast, behavioral therapies involving relaxation, most notably systematic desensitization, can be used to effectively treat ANV. Clinic personnel including oncologists and oncology nurses as well as behavioral psychologists can effectively administer systematic desensitization to chemotherapy patients.
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PMID:Models, mechanisms and management of anticipatory nausea and emesis. 869 50

A survey by Coates and co-workers in 1983 revealed that patients ranked nausea and vomiting as the most distressing side effects of chemotherapy. In the last decade the use of high-dose metoclopramide and, especially, the introduction of the 5-HT3 receptor antagonists, have been major leaps forward in the control of chemotherapy-induced emesis. Nevertheless, since patients still consider nausea and vomiting to be the most distressing side effect of their chemotherapy there is clearly a need for further improvements. Acute emesis, which is the topic of this review, can now be controlled in the majority of patients during their first course of chemotherapy. Future focus should be on better control of emesis during subsequent courses of chemotherapy as well as on better control of delayed emesis.
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PMID:Optimal control of acute cisplatin-induced emesis. 869 53

Since there continues to be a high incidence of postoperative nausea and vomiting associated with many types of surgery, and the standard antiemetics often do not achieve satisfactory results, there have been attempts to use the 5-HT3 antagonists. This group of substances is relatively new, but has already been used successfully as an antiemetic during chemotherapy. To date, results are on hand for four different 5-HT3 receptor blockers: ondansetron, tropisetron, granisetron and dolasetron. Applied intravenously, all four have been effective both in prophylaxis and also as therapy for postoperative emesis. Except for ondansetron, there is so far no definitely clear knowledge about the lowest possible effective dosage. The entire group is well tolerated: only occasional and minor side effects have been reported. Even though not all the hopes originally set in the 5-HT3 group of antagonists have been fulfilled, progress has nevertheless been achieved. Especially noteworthy points are a positive cost-effectiveness relationship of these drugs and their appropriate use in case of the proper indications.
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PMID:[Prevention and treatment of postoperative nausea and vomiting with 5-HT3-receptor blockers]. 870 77

In the latter part of the 20th century, significant advances have been made in the understanding of the emetic reflex. As a result, there have been major improvements in the treatment of vomiting, particularly that associated with chemo- and radiotherapeutic treatments for neoplastic disease. The 5-HT3 receptor antagonists (ondansetron and granisetron) have been demonstrated to be of benefit in treating the profound emesis observed during cancer treatment. This observation, together with results from pharmacologic and physiologic investigations in both animals and humans, have identified 5-hydroxy-tryptamine (5-HT or serotonin) to be of fundamental importance in the pathogenesis of emesis. 5-HT appears to be released by radiation and chemotherapeutic agents from enterochromaffin cells within the wall of the intestine, and possibly from neurons within the brainstem. Stimulation of 5-HT3 receptors, located centrally in the dorsal medulla of the brainstem and peripherally on vagal afferent terminals in the gastrointestinal tract, appears to play a pivotal role in eliciting emesis. The interaction of 5-HT with non-5-HT3 receptors, particularly 5-HT1A and 5-HT4 receptors, may be important in the emetic reflex. The development of agents that interact with these receptors may offer alternative approaches to the treatment of nausea and vomiting.
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PMID:Serotonergic mediation of vomiting. 870 63

An alternative on-line automated sample enrichment technique useful for the direct determination of various drugs and their metabolites in plasma is described for rapid development of highly sensitive and selective liquid chromatographic methods using mass spectrometric detection. The method involves direct injection of plasma onto an internal surface reversed-phase (ISRP) guard column, washing the proteins from the column to waste with aqueous acetonitrile, and backflushing the analytes onto a reversed-phase octyl silica column using switching valves. The analytes were detected using a tandem mass spectrometer operated in selected reaction monitoring (SRM) mode using atmospheric pressure chemical ionization (APCI). Use of two ISRP guard columns in parallel configuration allowed alternate injections of plasma samples on these columns for sample enrichment and shortened the column equilibration and LC-MS-MS analysis times, thereby increasing the sample throughput. The total run time, including both sample enrichment and chromatography, was about 6 min. Using this technique, an analytical method was developed for the quantitation of granisetron and its active 7-hydroxy metabolite in dog plasma. Granisetron is a selective 5-HT3 receptor antagonist used in the prevention and treatment of cytostatic induced nausea and vomiting. Recovery of the analytes was quantitative and the method displayed excellent linearity over the concentration ranges tested. Results from a three day validation study for both compounds demonstrated excellent precision (1.3-8.7%) and accuracy (93-105%) across the calibration range of 0.1 to 50 ng/ml using an 80 microliters plasma sample. The automated method described here was simple, reliable and economical. This on-line approach using ISRP columns and column switching with LC-MS-MS is applicable for the quantification of other pharmaceuticals in pharmacokinetic studies in animals and humans which require high sensitivity.
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PMID:Direct plasma liquid chromatographic-tandem mass spectrometric analysis of granisetron and its 7-hydroxy metabolite utilizing internal surface reversed-phase guard columns and automated column switching devices. 873 26

Most anticancer drugs are cytotoxic and produce various side-effects, among which nausea and vomiting are almost ubiquitous and usually extremely distressing to the patient. Cancer chemotherapy elicits two main phases of vomiting: an intense, acute phase of vomiting that occurs almost immediately following anti-cancer therapy and a milder, delayed phase of nausea and vomiting of longer duration. The mechanisms underlying the induction of nausea and vomiting after cancer chemotherapy are poorly understood but may be mediated by serotonin (5-hydroxytryptamine or 5-HT), particularly in the acute phase. Serotonin activates 5-HT3 receptors, which function as ligand-gated ion channels located either in the periphery and/or in the central nervous system to produce emesis, among other effects. The peripheral 5-HT3 receptors may be pharmacologically distinct from the central 5-HT3 receptors and may exhibit some association with GTP-binding proteins. In addition, different populations may exist as distinct subtypes of the same receptor. The 5-HT3 receptor antagonist ondansetron (GR 38032F) is effective in preventing the emesis induced by cytotoxic agents currently used in the treatment of many forms of cancer. Ondansetron has, comparatively, a much higher efficacy in the treatment of acute emesis following cancer chemotherapy than it does in the delayed phase, suggesting that the late phase of emesis may be mediated by other distinct mechanisms.
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PMID:Role of 5-hydroxytryptamine3 (5-HT3) antagonists in the prevention of emesis caused by anticancer therapy. 876 66

This paper reviews the toxicity profile of gemcitabine, a novel anticancer drug. Gemcitabine has been administered using two different treatment schedules: once weekly or twice weekly for 3 weeks followed by a week of rest (one cycle). It was well tolerated and alopecia was not a problem. Toxicity was greater in the twice-weekly schedule. Comparing the once-weekly with the twice-weekly schedule, WHO grade 3 or 4 thrombocytopenia was reported in 4.7 and 25.6% of patients, respectively. Other hematological toxicity was minimal. Transient WHO grade 3 or 4 elevations of ALT and AST occurred in 9.2 and 7.2% of patients, respectively, in the once-weekly schedule. For the twice-weekly schedule the corresponding percentages were 12.2 and 13.8%. Symptomatic toxicity was greater in patients who received twice-weekly gemcitabine. Nausea and vomiting was mild and generally well controlled without 5HT3 antagonists. However, there was a greater incidence of nausea and vomiting on the twice-weekly schedule. Flu-like symptoms were documented in 19.8% of patients receiving once-weekly and 63.3% of patients receiving twice-weekly gemcitabine. Peripheral edema, not related to cardiac, hepatic or renal failure, was seen more often in patients on twice-weekly treatment. As the efficacy of gemcitabine in non-small cell lung cancer was equivalent when using both regimens, the better tolerated and more easily administered once-weekly schedule is recommended.
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PMID:Gemcitabine: once-weekly schedule active and better tolerated than twice-weekly schedule. 879 11

In contrast to the broad experience concerning the therapeutic use of carboplatin, only limited data are available regarding the patterns of carboplatin-induced emesis, one of its most distressing side effects. This study reports frequency, severity and time course of carboplatin-induced vomiting and nausea refractory to 5-HT3 antagonism. A total of 216 patients receiving single-day carboplatin-based chemotherapy regimen were enrolled into an open multicenter study focusing on the safety and efficacy of ondansetron 8 mg t.d.s. Emesis on day 1 occurred in 22% and nausea in 75% of the patients; 44% of patients reported some degree of vomiting within the 5 days observation period. The risk for emesis and nausea over 2-5 days was increased in patients suffering from emesis on day 1 (relative risk 2.25 for vomiting and 2.84 for nausea, respectively). The median cumulative number of emetic episodes was 0 for all patients and 4 for the patients who did vomit at least on 1 day. Vomiting began on average 1.77 days following chemotherapy administration. The mean duration of vomiting was 2 days and 3.1 days for nausea. Carboplatin showed a monophasic prolonged pattern of emesis. The combination with cyclophosphamide led to an earlier onset and a higher frequency of vomiting. The analysis of the pattern of emesis refractory to 5-HT3 receptor blockade should help to describe the course of emesis, which is probably triggered through a 5-HT3 receptor-independent mechanisms.
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PMID:Pattern of carboplatin-induced emesis. The German Ondansetron Study Group. 884 74

Nausea and vomiting are the most frequently reported adverse effects of cancer chemotherapy and have a significant impact on patients' daily functioning, quality of life and compliance with chemotherapy. Summarized in this article are the recommendations for the optimal management of nausea and vomiting developed by a multidisciplinary group of health care professionals. Issues relating to chemotherapy-induced nausea and vomiting are discussed; general principles of treatment are reviewed; treatment algorithms based on emetogenicity and types of chemotherapy are presented; and the importance of issues including non-pharmacological approaches, patient education and pharmacoeconomic perspectives are considered. The goal of antiemetic therapy should be no episodes of vomiting or retching and minimal or no nausea. Data from clinical trials support the clear superiority of 5-HT3 receptor antagonists in a variety of clinical situations. Their cost must be considered not only as an isolated item from the institutional perspective, but also from the perspective of the impact of successful therapy on the patient.
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PMID:Guidelines for the optimal management of chemotherapy-induced nausea and vomiting: a consensus. 885 13

Efficiency of ondansetron, a selective 5-HT3 receptor antagonist, in prevention of postoperative nausea and vomiting in 40 ASA I-II patients who will undergo emergency intraabdominal operations is studied in a randomized double-blind and placebo controlled study. Patients of no premedication are administered 4 mg i.v. ondansetron or placebo (saline) before induction. Thiopental (4 mg/kg) was used for induction, succinylcholine (2 mg/kg) for muscular relaxation, and 50% nitrous oxide in oxygen and isoflurance (0.8-1.5%) for the maintenance of anesthesia, and fentanyl and norcuron were administered when necessary. Vital signs were closely monitored and recorded during anesthesia and early postoperative period. Study is carried out during postoperative 0-1 h, 1-2 h and 2-24 h periods. Nausea scores and emesis were recorded during 0-1 and 1-2 h periods. Ondansetron was found significantly more effective than placebo (p < 0.05 and p < 0.05). Although is was effective during 2-24 h period, the difference was not statistically significant (p > 0.05). No significant difference was observed between the groups in terms of vital findings, laboratory findings and side effects (p > 0.05). Therefore it is concluded that administration of prophylactic i.v. ondansetron to patients undergoing emergency intraabdominal operations is effective in prevention of nausea and vomiting without any significant side effects.
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PMID:Prophylactic administration of ondansetron in emergency intraabdominal operations. 899 79


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