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Medicine Feb 2019We aimed to perform a network meta-analysis (NMA) to quantify and rank the efficacy and safety of the pharmacologic interventions for prophylactic use for postoperative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aimed to perform a network meta-analysis (NMA) to quantify and rank the efficacy and safety of the pharmacologic interventions for prophylactic use for postoperative nausea and vomiting (PONV) in patients undergoing thyroidectomies.
METHODS
A systematic and comprehensive search will be performed using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar, beginning from their inceptions to February 2019. Only randomized clinical trials on the efficacy and safety of pharmacologic interventions for prophylactic use in patients undergoing thyroidectomies will be included.The primary endpoints will be the incidences of postoperative nausea (PON), postoperative vomiting (POV), and PONV in the early, middle, late, and overall phases. The severity of PON, POV, and PONV; the use of rescue antiemetics; the incidence of complete response; and safety issues, such as headache, dizziness, drowsiness, and constipation, will be also assessed.We will conduct both pairwise meta-analysis and NMA. We will use surface under the cumulative ranking curve (SUCRA) values and rankograms to present the hierarchy of pharmacologic interventions. A comparison-adjusted funnel plot will be used to assess the presence of small-study effects. The quality of the studies included will be assessed using the risk of bias tool 2.0. All statistical analyses will be performed using Stata SE version 15.0.
RESULTS
The results of this systematic review and NMA will be published in a peer-reviewed journal.
CONCLUSION
This systematic review and NMA will provide a comprehensive and convincing evidence summary of prophylactic pharmacologic interventions for PONV after a thyroidectomy.
TRIAL REGISTRATION NUMBER
CRD42018100002.
Topics: Antiemetics; Humans; Network Meta-Analysis; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Thyroidectomy
PubMed: 30762797
DOI: 10.1097/MD.0000000000014542 -
British Journal of Clinical Pharmacology Jun 19941. Selective 5-HT3-receptor antagonists are highly effective in preventing nausea and vomiting associated with chemotherapy, radiotherapy and surgery. Their... (Review)
Review
1. Selective 5-HT3-receptor antagonists are highly effective in preventing nausea and vomiting associated with chemotherapy, radiotherapy and surgery. Their pharmacological activity may be determined in vitro and in animal models of emesis. However, these methods may not give an accurate indication of the antiemetic dose range of 5-HT3-receptor antagonists in patients. Two volunteer models have been used to predict more accurately clinically effective antiemetic doses of 5-HT3-receptor antagonists. 2. The flare response to intradermal 5-HT is thought to be mediated by excitation of 5-HT3-receptors on cutaneous afferents, with release of substance P and subsequent vasodilation. Antagonism of the flare response appears to provide an indication of the effective antiemetic dose of 5-HT3-receptor antagonists but data on duration of action are conflicting. 3. Ipecacuanha-induced emesis is thought to be mediated through both peripheral and central 5-HT3-receptors. Antagonism of this response has demonstrated a close correlation with clinically effective antiemetic doses of the specific 5-HT3-receptor antagonist, ondansetron, and has the advantage of being more conceptually relevant than the flare model. 4. Further work, with newer 5-HT3-receptor antagonists, will clarify the role of these models as predictive of the use of these drugs in clinical practice.
Topics: Antiemetics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Injections, Intradermal; Ipecac; Predictive Value of Tests; Reference Values; Serotonin Antagonists; Vomiting
PubMed: 7917768
DOI: 10.1111/j.1365-2125.1994.tb04298.x -
Journal of Pain and Symptom Management Mar 2012Cyclizine, an antihistaminic antiemetic, is commonly used in palliative care. Its pharmacokinetics have been poorly studied, and its metabolic pathway is unknown but may...
CONTEXT
Cyclizine, an antihistaminic antiemetic, is commonly used in palliative care. Its pharmacokinetics have been poorly studied, and its metabolic pathway is unknown but may involve the genetically controlled cytochrome P450 2D6 (CYP2D6). If this is the case, the metabolic ratio of cyclizine to norcyclizine and efficacy/adverse effects may vary between patients according to their CYP2D6 genotype.
OBJECTIVES
To deduce the pharmacokinetics and antiemetic/sedative effects of cyclizine and relate these and its metabolic ratio to the CYP2D6 genotype in palliative care patients.
METHODS
Palliative care patients initiated on continuous cyclizine subcutaneous (SC) infusions had blood samples taken and efficacy/toxicity scores measured during the approach to steady state. Another group of patients at steady state receiving oral cyclizine had a single blood sample taken. Samples were analyzed to elucidate pharmacokinetic parameters and CYP2D6 genetics.
RESULTS
SC dosing group: The median (interquartile range) cyclizine half-life, volume of distribution, and clearance were 13 (7-48) hours, 23 (12-30)L/kg, and 15 (11-26)mL/min/kg, respectively. Nausea and sedation scores were 3.0 (1.2-5.7) and 5.0 (2.6-8.1), respectively, overall and did not vary with genotype (P=0.76 and 0.11, respectively). The median overall metabolic ratio at steady state was 4.9 (3.8-9.2) and did vary with CYP2D6 genotype (P=0.02). Oral dosing group: The median metabolic ratio was 2.1 (1.5-2.9) and did not vary with CYP2D6 genotype (P=0.37).
CONCLUSION
Palliative care patients have similar cyclizine pharmacokinetics to those reported in other patient groups. Cyclizine metabolism to norcyclizine may include CYP2D6 as the metabolic ratio varied with CYP2D6 genotype in the SC group.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antiemetics; Chromatography, High Pressure Liquid; Cyclizine; Cytochrome P-450 CYP2D6; DNA; Dose-Response Relationship, Drug; Female; Genotype; Half-Life; Humans; Infusions, Subcutaneous; Male; Middle Aged; Palliative Care; Pharmacogenetics; Tandem Mass Spectrometry
PubMed: 22209223
DOI: 10.1016/j.jpainsymman.2011.04.022 -
British Journal of Clinical Pharmacology Jul 2017The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV). (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV).
METHODS
The literature was searched for randomized controlled trials (RCTs) evaluating the efficacy of olanzapine for the prophylaxis of CINV using PubMed, Embase, Central, as well as clinicaltrials.gov for unpublished studies. The endpoints of the study were the number of patients who achieved a complete response (CR; no emesis and no rescue) and no nausea in the acute, delayed and overall phases. Two authors independently selected studies, assessed the risk of bias and extracted data. The included RCTs were analysed using RevMan 5.3 provided by the Cochrane Collaboration.
RESULTS
Ten RCTs were identified for the meta-analysis. Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase. For the control of CINV, olanzapine was better than and comparable with aprepitant in the acute phase and delayed phase, respectively. Compared with placebo, treatment with 5 mg and 10 mg olanzapine exhibited similar efficacy in terms of the CR in the delayed and overall phases.
CONCLUSIONS
Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Nausea; Neoplasms; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting
PubMed: 28112422
DOI: 10.1111/bcp.13242 -
British Journal of Pharmacology Jul 2009Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics... (Review)
Review
Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms.
Topics: Animal Experimentation; Animal Husbandry; Animals; Antiemetics; Disease Models, Animal; Humans; Nausea; Species Specificity; Vomiting
PubMed: 19371333
DOI: 10.1111/j.1476-5381.2009.00176.x -
Basic & Clinical Pharmacology &... Sep 2007Nausea and vomiting are ranked as the most severe side effects to chemotherapy by cancer patients. Twenty years ago, treatment of nausea and vomiting from chemotherapy... (Review)
Review
Nausea and vomiting are ranked as the most severe side effects to chemotherapy by cancer patients. Twenty years ago, treatment of nausea and vomiting from chemotherapy only had moderate effect and often unpleasant side effects. The drugs used included dopamine(2)-receptor antagonists and corticosteroids alone or combined. This review summarizes the development of anti-emetic therapy, but will focus on the importance of two new classes of anti-emetics: the serotonin(3)- and the neurokinin(1)-receptor antagonists. Furthermore, evidence-based guidelines for the treatment of chemotherapy-induced nausea and vomiting will be given. The serotonin(3)-receptor antagonists, the first group of drugs developed specifically as anti-emetics, have significantly improved the prophylaxis of chemotherapy-induced emesis especially in combination with a corticosteroid. The improvement in the prophylaxis of nausea with this combination is however modest. A new group of anti-emetics, the neurokinin(1)-receptor antagonists, has now been developed, and the first drug, aprepitant, was marketed in 2003. Aprepitant increases the effect of a serotonin(3)-receptor antagonist plus a corticosteroid against acute emesis induced by highly or moderately emetogenic chemotherapy and aprepitant is also active in the protection against delayed emesis. The importance of drug-drug interactions with anti-emetics and other drugs, especially cytotoxins, through their competition for cytochrome P450 enzymes, have been studied. At present, there is no evidence that such interactions are of major clinical importance. Evidence-based clinical guidelines are now available and regularly updated, but unfortunately clinical implementation is slow. Recommendations for some types of chemotherapy-induced emesis such as delayed emesis, is based on a low level of evidence. Furthermore, the majority of clinical trials include highly selected groups of patients not permitting definite conclusions for other and more heterogeneous patient groups. Development of new anti-emetics with other mechanisms of action is awaited with interest.
Topics: Antiemetics; Antineoplastic Agents; Drug Interactions; Evidence-Based Medicine; Humans; Nausea; Neurokinin-1 Receptor Antagonists; Practice Guidelines as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 17697032
DOI: 10.1111/j.1742-7843.2007.00122.x -
Supportive Care in Cancer : Official... May 2017Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT) receptor... (Review)
Review
Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NKRAs when combined with 5-HTRA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NKRAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NKRAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.
Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Neurokinin-1 Receptor Antagonists; Quality of Life; Vomiting
PubMed: 28108820
DOI: 10.1007/s00520-017-3585-z -
The Journal of Clinical Psychiatry Jun 2020Ondansetron is a 5-HT₃ receptor antagonist that has been approved for the prevention of nausea and vomiting associated with cancer chemotherapy, radiotherapy, and... (Review)
Review
Ondansetron is a 5-HT₃ receptor antagonist that has been approved for the prevention of nausea and vomiting associated with cancer chemotherapy, radiotherapy, and surgery. Ondansetron has also been studied in the treatment of many neuropsychiatric and medical conditions. The drug is commonly used off-label to treat nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG). Ondansetron crosses the placental barrier, and concerns have been expressed that using ondansetron for NVP/HG during the first trimester of pregnancy may increase the risk of major congenital malformations (MCMs) in the offspring. In this context, findings from a meta-analysis of 6 cohort and 2 case-control studies, read along with the results of subsequently published cohort (n = 3) and case-control (n = 1) studies, suggest that a signal does exist to associate early gestational exposure to ondansetron with an increased risk of heart defects and orofacial defects. Arguments both for and against confounding by indication have been proposed to explain these findings. Nevertheless, even if ondansetron is causally implicated in MCM risk, the absolute increase in risk, such as for orofacial clefts (by 0.03%) and ventricular septal defect (by 0.3%), is small. These small risks should be balanced against the risks associated with inadequately treated NVP/HG, and decision-making must be shared between clinician and patient. Repeated fetal scanning during the second trimester can help in the early detection of malformations, if present.
Topics: Abnormalities, Drug-Induced; Administration, Intravenous; Administration, Oral; Antiemetics; Female; Humans; Morning Sickness; Ondansetron; Pregnancy; Pregnancy Trimester, First; Risk Factors
PubMed: 32526103
DOI: 10.4088/JCP.20f13472 -
Clinics (Sao Paulo, Brazil) 2024The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic review and meta-analysis, the authors evaluate the efficacy and side effects of olanzapine as a prophylactic antiemetic in adult patients who undergo general anesthesia and assess adverse effects.
METHODS
A systematic search was done on electronic bibliographic databases in July 2023. Randomized controlled trials of olanzapine as a prophylactic antiemetic for PONV in adults who underwent general anesthesia were included. The authors excluded non-RCTs and retracted studies. The authors set no date of publication or language limits. The outcomes were the incidence of PONV within 24 h postoperatively and the safety of olanzapine. The risk of bias was assessed according to the tool suggested by the National Heart, Lung, and Blood Institute.
RESULTS
Meta-analysis included 446 adult patients. Olanzapine reduced on average 38 % the incidence of PONV. The estimated risk ratio (95 % CI) of olanzapine versus control was 0.62 (0.42-0.90), p = 0.010, I = 67 %. In the subgroup meta-analysis, doses of olanzapine (10 mg) reduced on average 49 % of the incidence of PONV (RR = 0.51 [0.34-0.77], p = 0.001, I = 31 %).
CONCLUSIONS
This systematic review with meta-analysis indicated that olanzapine as a prophylactic antiemetic alone or combined with other antiemetic agents reduced the incidence of postoperative nausea and vomiting. However, this conclusion must be presented with some degree of uncertainty due to the small number of studies included. There was a lack of any evidence to draw conclusions on side effects.
Topics: Adult; Humans; Antiemetics; Postoperative Nausea and Vomiting; Olanzapine; Anesthesia, General
PubMed: 38513297
DOI: 10.1016/j.clinsp.2024.100345 -
Oncology (Williston Park, N.Y.) Mar 2018The approach to the treatment of nausea and vomiting in a cancer patient should begin with a complete assessment, including the frequency, duration, and intensity of the...
The approach to the treatment of nausea and vomiting in a cancer patient should begin with a complete assessment, including the frequency, duration, and intensity of the nausea/vomiting; associated activities; and whether anorexia or cachexia is present. It is important to determine whether the nausea and vomiting is related to treatment (chemotherapy, radiation) or is independent of cancer treatment. Nausea/vomiting unrelated to chemotherapy and/or radiation may have an etiology for which there is a specific and potentially successful intervention. Various national and international antiemetic guidelines have been developed for the prevention of chemotherapy- and radiotherapy-induced nausea and emesis. The antiemetics recommended in these guidelines (5-hydroxytryptamine type 3 receptor antagonists, neurokinin-1 receptor antagonists, dexamethasone) have significantly reduced emesis but not nausea. Recent randomized clinical trials have demonstrated that olanzapine may be an effective agent for the prevention and treatment of chemotherapy-induced nausea as well as emesis.
Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Neoplasms; Radiotherapy; Vomiting
PubMed: 29548068
DOI: No ID Found