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

Ondansetron is a highly potent and selective antagonist at 5-HT3 receptors. Its anti-emetic actions were first revealed by its ability to antagonize retching and vomiting induced by chemotherapy and radiotherapy in animals and man. Subsequently, the availability of labelled 5-HT3 receptor ligands allowed identification of 5-HT3 receptors, located at highest densities in the area postrema, nucleus tractus solitarius (NTS), in other areas of the brain, and on afferent terminals of the vagus nerve. Postoperative nausea and vomiting may be caused by various factors: the anaesthetic, associated drugs, the surgical procedure, movement of the patient, sex, weight and pain. These factors mediate their effects via the higher brain circuits, the vestibular nuclei, the chemoreceptor trigger zone in the area postrema, or the upper gastrointestinal tract via the vagus nerve, influencing motor and visceral emetic outputs in the hind-brain. It is hypothesized that ondansetron blocks nausea and vomiting by 5-HT3 receptor antagonism at two specific sites: (i) centrally, in the area postrema/NTS; and (ii) peripherally on vagus nerve terminals. The absence of other pharmacological effects of ondansetron ensures an absence of side-effects.
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PMID:Pharmacology of ondansetron. 142 23

Postoperative nausea and vomiting is a major concern for patients undergoing outpatient surgery under general anaesthesia, and may complicate and delay discharge from hospital. This paper evaluates the safety and efficacy of ondansetron, a 5-HT3 receptor antagonist, in the treatment of postoperative nausea and vomiting. One thousand patients in 30 centres in the United States who received general anaesthesia and developed postoperative nausea and vomiting were studied. In a randomised, double-blind, stratified and parallel designed protocol, patients received either ondansetron 1, 4, 8 mg or placebo for nausea or vomiting occurring within 2 h of entry into the Post Anaesthesia Care Unit. Subsequent episodes of vomiting, nausea scores, laboratory and clinical safety data and adverse events were evaluated during the 24-h study period. In a separate study, pharmacokinetic data were compared for intramuscularly and intravenously administered ondansetron. Each dose of ondansetron was significantly better than placebo in reducing nausea from control values during the initial 2-h study period, and in preventing further emesis over 24 h. There were no significant differences in the incidence of adverse events, changes in laboratory values or measures of vital signs in the ondansetron groups compared to the placebo group. Dose comparisons between the three treatment groups showed that ondansetron 4 mg is the optimal dose to treat postoperative nausea and vomiting. Ondansetron is a well tolerated, efficacious antiemetic which has a similar side effect profile to placebo. Intramuscular administration has the same systemic availability as intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Single dose intravenous ondansetron for the 24-hour treatment of postoperative nausea and vomiting. 812 59

Minimally invasive therapy aims to minimize the trauma of any interventional process but still achieve a satisfactory therapeutic result. The development of "critical pathways," rapid mobilization and early feeding have contributed towards the goal of shorter hospital stay. This concept has been extended to include laparoscopic cholecystectomy and hernia repair. Reports have been published confirming the safety of same day discharge for the majority of patients. However, we would caution against overenthusiastic ambulatory laparoscopic cholecystectomy on the rational but unproven assumption that early discharge will lead to occasional delays in diagnosis and management of postoperative complications. Intraoperative complications of laparoscopic surgery are mostly due to traumatic injuries sustained during blind trocar insertion and physiologic changes associated with patient positioning and pneumoperitoneum creation. General anesthesia and controlled ventilation comprise the accepted anesthetic technique to reduce the increase in PaCO2. Investigators have recently documented the cardiorespiratory compromise associated with upper abdominal laparoscopic surgery, and particular emphasis is placed on careful perioperative monitoring of ASA III-IV patients during insufflation. Setting limits on the inflationary pressure is advised in these patients. Anesthesiologists must maintain a high index of suspicion for complications such as gas embolism, extraperitoneal insufflation and surgical emphysema, pneumothorax and pneumomediastinum. Postoperative nausea and vomiting are among the most common and distressing symptoms after laparoscopic surgery. A highly potent and selective 5-HT3 receptor antagonist, ondansetron, has proven to be an effective oral and IV prophylaxis against postoperative emesis in preliminary studies. Opioids remain an important component of the anesthesia technique, although the introduction of newer potent NSAIDs may diminish their use. A preoperative multimodal analgesic regimen involving skin infiltration with local anesthesia. NSAIDs to attenuate peripheral pain and opioids for central pain may reduce postoperative discomfort and expedite patient recovery/discharge. There is no conclusive evidence to demonstrate clinically significant effects of nitrous oxide on surgical conditions during laparoscopic cholecystectomy or on the incidence of postoperative emesis. Laparoscopic cholecystectomy has proven to be a major advance in the treatment of patients with symptomatic gallbladder disease.
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PMID:Anesthetic implications of laparoscopic surgery. 1060 86

Postoperative nausea and vomiting (PONV) affects approximately one third of patients and may lead to aspiration, dehiscence, esophageal rupture, and increased treatment costs if inadequately controlled. An important therapeutic option for prevention of PONV is 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists. Nonetheless, therapeutic failure sometimes occurs. Metabolism by the cytochrome P450 (CYP) system differs among the 5-HT3 receptor antagonists, and provides a rational explanation for decreased therapeutic efficacy in some patients. Four of the 5-HT3 receptor antagonist agents (dolasetron, ondansetron, palonosetron, and tropisetron) are metabolized in various degrees via CYP2D6, an isoform subject to marked genetic polymorphism. In patients with duplicate CYP2D6 alleles, degradation into inactive metabolites occurs rapidly with these four 5-HT3 receptor antagonists, resulting in decreased efficacy for preventing PONV. Granisetron is the only agent in this class that is not metabolized via CYP2D6. Instead, granisetron is metabolized via the CYP3A4 isoform, which is not subject to significant genetic polymorphism. CYP2D6 genotype screening prior to PONV treatment may allow for modification of antiemetic dosing. An alternative is to use a 5-HT3 agent that is metabolized independently of the CYP2D6 isoform, such as granisetron, that would obviate the need for genotyping and may lead to improved prophylaxis of PONV.
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PMID:Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. 1619 15

Postoperative nausea and vomiting (PONV) is a frequent complication of surgery. Guidelines recommend using a 5-HT3 receptor antagonist (eg, ondansetron, dolasetron, granisetron) combined with a second agent (eg, dexamethasone) for patients at moderate to high risk for PONV. Although all 5-HT3 antagonists are effective, ondansetron and granisetron have been found to be effective at substantially lower doses than those approved by the US Food and Drug Administration. Metabolism of granisetron differs from metabolism of other 5-HT, antagonists, so it is less likely to adversely interact with other medications. This article explains the clinical pharmacology of 5-HT3 antagonists and provides recommendations for nursing management of PONV.
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PMID:The role of 5-HT3 receptor antagonists in preventing postoperative nausea and vomiting. 1652 8

Postoperative nausea and vomiting (PONV) continues to be a "big little problem" despite recent advances in anesthesia. Because of an increased interest in, and the abundant publications on this topic, guidelines for the management of PONV were published in 2003. Several key but controversial issues regarding PONV prophylaxis were left unaddressed, however. These included whether clinical differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonists, concern over optimal dosage and timing of administration, optimal 5-HT3 receptor antagonist combination therapy, and whether rescue therapy is effective after prior administration of the same or a different 5-HT3 receptor antagonist. The application of these antiemetics in clinical practice has raised questions regarding the role of the 5-HT3 receptor antagonists in the treatment of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A brief overview of the incidence, risk factors and current management recommendations for PONV and current controversies with special emphasis on the 5-HT3 receptor antagonists, is discussed.
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PMID:Prophylaxis of postoperative nausea and vomiting: controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists. 1679 35

Postoperative nausea and vomiting (PONV) continues to be a most common complication of surgery and anesthesia. It has been suggested that the inherited factors may play a significant role in the background sensitivity to both PONV and also chemotherapy-induced nausea and vomiting (CINV), including resistance to antiemetic prophylaxis and/or therapy. This notion could be best exemplified by occurrence of PONV in several generations of families and concordance of PONV in monozygotic twins. The most frequently addressed issue in the research on genomic background of PONV/CINV relates to the inherited resistance to the antiemetic treatment (pharmacogenomics), and in lesser degree to their genomic background. The most common group of antiemetics consists of 5HT3 receptor antagonists, and this group was an initial target of pharmacogenomic research. Most research approaches have been based on the investigation of polymorphic variations in the target for the antiemetic 5HT3 receptor antagonists, i.e., serotonin receptor subunits A and B (HTR3A and HTR3B). The other area of pharmacogenomic investigations includes metabolic pathways of 5HT3 antagonists, in particular polymorphic variants of the CYP450 2D6 isoform (CYP2D6) because most of them are metabolized in various degrees by the CYP2D6 system. The results of targeted genomic association studies indicate that other genes are also associated with PONV and CINV, including OPRM1, and ABCB1. In addition, genes such as DRD2 and CHRM3 genes have recently been associated with PONV. The new genome-wide association studies seem also to indicate that the background genomic sensitivity to PONV and CINV might be multifactorial and include several genomic pathways.
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PMID:Genetic factors associated with pharmacotherapy and background sensitivity to postoperative and chemotherapy-induced nausea and vomiting. 2479 5

Postoperative nausea and vomiting (PONV) is a debilitating condition that occurs in approximately 30% of patients undergoing general anesthesia. Premedication with 5-HT3 receptor antagonists and glucocorticoids is effective in clinical practice; however, 10% to 20% of patients still develop PONV. Currently, little is known about the treatment of refractory PONV. We present a case that illustrates the use of fosaprepitant for the treatment of refractory postoperative nausea and vomiting.
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PMID:Fosaprepitant for the Treatment of Refractory Postoperative Nausea and Vomiting. 2640 12

Postoperative nausea and vomiting (PONV) is a common complication in paediatric anaesthesia and is a source of significant morbidity. Various independent risk factors have been implicated in the development of paediatric PONV, including higher pain scores postoperatively, the use of opioids for pain management and the use of volatile anaesthetics for the maintenance of anaesthesia. This review of the current literature regarding the prevention and treatment of paediatric PONV is based on a search of the PubMed database, which identified published clinical trials, systematic reviews and meta-analyses. While the occurrence of PONV in many cases is difficult to avoid entirely, the risk can be mitigated by the use of multimodal nonopioid analgesic regimens, total intravenous drugs in favour of volatile anaesthetics and an appropriate regimen of prophylactic pharmacotherapy. Frequently administered drug classes for the prevention of PONV include corticosteroids, 5HT3 antagonists and anticholinergics. The clinical use of the findings in the literature may help to reduce the occurrence of PONV in children. In this review, we provide comprehensive and updated information on the risk factors contributing the occurrence of PONV in children, outline the current opinion on the drugs that are commonly used for management and provide an overview of the guidelines that are used to help establish the prophylaxis and treatment of paediatric PONV.
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PMID:Postoperative Nausea and Vomiting in Paediatric Anaesthesia. 3225 38

Postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) are frequent unpleasant complaints that patients and clinicians report after surgery. PONV and PDNV have been associated with postoperative complications and hospital discharge delays. Despite the extensive evidence describing the use of several regimens in different surgical populations, the ideal regimen has not been established. Several antiemetic drugs have been evaluated in more than 1000 clinical controlled trials for management of this complex emetogenic pathway, including the 5-hydroxytryptamine (5-HT3) receptor antagonists, dopamine receptor antagonists, neurokinin-type receptor antagonists, antihistaminics, anticholinergics, and corticosteroids, with the 5-HT3 receptor antagonists being the most commonly used for PONV prophylaxis. Because of the complex emetogenic pathway and multifactorial etiology of PONV, a multimodal approach using two or more drugs that act at different neuro-receptor sites is suggested in patients with one or more risk factors to successfully address PONV and reduce its incidence. Nevertheless, the most studied regimens in randomized clinical trials (RCTs) are the combination of serotonin 5-HT3 receptor antagonists with dexamethasone or dopamine receptor antagonists (droperidol). Therefore, the safest and more effective combination regimen appears to be the use of serotonin 5-HT3 receptor antagonist antiemetic drugs with dexamethasone.
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PMID:What is the ideal combination antiemetic regimen? 3328 20


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