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British Journal of Clinical Pharmacology Feb 2021Changes in serotonergic sensory modulation associated with overexpression of 5-HT receptors in the central nervous system (CNS) have been implicated in the...
AIMS
Changes in serotonergic sensory modulation associated with overexpression of 5-HT receptors in the central nervous system (CNS) have been implicated in the pathophysiology of neuropathic pain after peripheral nerve damage. 5-HT receptor antagonists such as ondansetron can potentially alleviate neuropathic pain, but have limited effectiveness, due potentially to limited CNS access. However, there is currently limited information on CNS disposition of systemically-administered 5-HT receptor antagonists. This study evaluated the cerebrospinal fluid (CSF) disposition of ondansetron, as a surrogate of CNS penetration.
METHODS
Fifteen patients were given a single 16 mg intravenous 15 minute infusion of ondansetron, followed by serial blood and a single CSF sampling. Population pharmacokinetic (PK) modelling was implemented to describe the average and individual plasma and CSF profiles of ondansetron. A two-compartmental model was used to capture ondansetron plasma PK with a single CSF compartment to describe distribution to the CNS.
RESULTS
The individual model-estimated CSF to plasma partition coefficients of ondansetron were between 0.09 and 0.20. These values were mirrored in the calculated CSF penetration ratios, ranging from 0.08 to 0.26.
CONCLUSIONS
After intravenous administration, CSF concentrations of ondansetron were approximately 7-fold lower than those observed in the plasma. A model could be developed to describe individual CSF concentration-time profiles of ondansetron based on a single CSF data point. The low CSF penetration of ondansetron may explain its limited analgesic effectiveness, and affords an opportunity to explore enhancing its CNS penetration for targeting conditions such as neuropathic pain.
Topics: Administration, Intravenous; Humans; Infusions, Intravenous; Neuralgia; Ondansetron; Plasma
PubMed: 32495990
DOI: 10.1111/bcp.14412 -
Neuropsychopharmacology : Official... Jan 2019Several psychiatric disorders involve abnormalities of interoception and associated neural circuitry centered on the insula. The development of interventions modulating... (Randomized Controlled Trial)
Randomized Controlled Trial
Several psychiatric disorders involve abnormalities of interoception and associated neural circuitry centered on the insula. The development of interventions modulating interoceptive circuits could lead to novel treatment approaches for these disorders. The 5-HT3 receptor antagonist ondansetron is a good candidate for the modulation of interoceptive circuits, as 5-HT3 receptors are located abundantly on sensory pathways and ondansetron has shown some clinical utility in disorders characterized by sensory and interoceptive abnormalities. The present study tested the ability of three different doses of ondansetron to engage neural regions involved in interoception to determine the drug's utility as a therapeutic agent to target circuit abnormalities in patients. Fifty-three healthy subjects were randomized to receive a single 8-mg (n = 18), 16-mg (n = 17), or 24-mg (n = 18) dose of ondansetron and placebo before MRI scanning on separate days. Subjects performed an fMRI task previously shown to engage interoceptive circuitry in which they viewed videos depicting body movements/sensation and control videos. The results revealed a highly significant relationship between dosage and activation in bilateral insula, somatosensory and premotor regions, cingulate cortex, and temporal cortex for control but not body-focused videos. These effects were driven by a robust reduction in activation for ondansetron compared to placebo for the 24-mg group, with weaker effects for the 16-mg and 8-mg groups. In conclusion, high-dose ondansetron reduces activation of several areas important for interoception, including insula and sensorimotor cortical regions. This study reveals the potential utility of this drug in modulating hyperactivity in these regions in patients.
Topics: Adult; Brain; Female; Humans; Interoception; Magnetic Resonance Imaging; Male; Ondansetron; Serotonin Antagonists; Young Adult
PubMed: 30116006
DOI: 10.1038/s41386-018-0174-x -
American Family Physician Jul 2003Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed,... (Review)
Review
Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed, the exact cause remains unclear. Recent research has implicated Helicobacter pylori as one possible cause. Nausea and vomiting of pregnancy is generally a mild, self-limited condition that may be controlled with conservative measures. A small percentage of pregnant women have a more profound course, with the most severe form being hyperemesis gravidarum. Unlike morning sickness, hyperemesis gravidarum may have negative implications for maternal and fetal health. Physicians should carefully evaluate patients with nonresolving or worsening symptoms to rule out the most common pregnancy-related and nonpregnancy-related causes of severe vomiting. Once pathologic causes have been ruled out, treatment is individualized. Initial treatment should be conservative and should involve dietary changes, emotional support, and perhaps alternative therapy such as ginger or acupressure. Women with more complicated nausea and vomiting of pregnancy also may need pharmacologic therapy. Several medications, including pyridoxine and doxylamine, have been shown to be safe and effective treatments. Pregnant women who have severe vomiting may require hospitalization, orally or intravenously administered corticosteroid therapy, and total parenteral nutrition.
Topics: Acupressure; Antiemetics; Diagnosis, Differential; Doxylamine; Female; Zingiber officinale; Humans; Hyperemesis Gravidarum; Nausea; Ondansetron; Pregnancy; Pregnancy Complications; Vomiting
PubMed: 12887118
DOI: No ID Found -
Pediatric Emergency Care Mar 2020Ondansetron has been shown to decrease admission rate and the need for intravenous fluids among pediatric emergency department (ED) patients with acute gastroenteritis,...
OBJECTIVES
Ondansetron has been shown to decrease admission rate and the need for intravenous fluids among pediatric emergency department (ED) patients with acute gastroenteritis, but there is limited evidence regarding its use after ED discharge. This study describes prescribing patterns for ondansetron and assesses the effects of ondansetron home prescription on rate of return.
METHODS
Data were gathered from the electronic health record on 2 separate but overlapping groups of patients seen in a pediatric ED from 2012 to 2014. The Gastroenteritis Group included all patients with a discharge diagnosis of gastroenteritis by International Classification of Diseases, Ninth Revision, code. The All Ondansetron Group included any child prescribed ondansetron at discharge. Patterns of ondansetron use and 3- and 7-day ED return rate were assessed for both groups. Discharge diagnosis was evaluated for the All Ondansetron Group.
RESULTS
A total of 996 patients with acute gastroenteritis were identified during the study period. Of these, 76% received ondansetron in the ED, and 71% were discharged with prescriptions for ondansetron. Seven-day ED return rates were similar between groups (6% with prescription, 5% without, P = 0.66). A total of 2287 patients received home prescriptions for ondansetron. Fifty-four percent of these patients' discharge diagnoses were classed as gastrointestinal complaints, 14% other infectious conditions, 9% respiratory, and 4% injuries. Their return rate was 6%. There was wide variation in the number of doses prescribed.
CONCLUSIONS
Home-use ondansetron is widely prescribed in this urban academic pediatric ED for a variety of indications, without effect on 3- or 7-day ED return. Further prospective studies are necessary to determine the efficacy of this practice.
Topics: Adolescent; Antiemetics; Child; Child, Preschool; Electronic Health Records; Emergency Service, Hospital; Female; Gastroenteritis; Humans; Infant; Infant, Newborn; Male; Ondansetron; Patient Discharge; Retrospective Studies; Vomiting
PubMed: 29135900
DOI: 10.1097/PEC.0000000000001343 -
The efficacy of aprepitant for the prevention of postoperative nausea and vomiting: A meta-analysis.Medicine Jul 2023Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs suggest that aprepitant has the strongest antiemetic effect of any single drug. This meta-analysis aimed to explore the efficacy of aprepitant for preventing PONV based on the existing literature.
METHODS
To identify RCTs investigating the use of aprepitant for PONV prevention, we searched PubMed, Embase, and Cochrane Library databases for articles published prior to March 20, 2022. Seventeen RCTs were identified, with 3299 patients, meeting the inclusion criteria. PONV incidence, complete response, 80 mg aprepitant combined with dexamethasone and ondansetron, vomiting, nausea, and analgesic dose-response were the main outcomes measured.
RESULTS
Compared with the control group, PONV incidence was significantly reduced among those receiving aprepitant (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.26, 0.44; P < .0001), with a more complete response (OR: 1.35; 95% CI: 1.14, 1.59; P = .0004). Supplementation of 80 mg aprepitant in combination with dexamethasone and ondansetron substantially improved the effects of PONV (OR: 0.36; 95% CI: 0.16, 0.82; P = .01). Further, administration of 80 mg aprepitant was better at preventing vomiting than nausea (OR: 8.6; 95% CI: 3.84, 19. 29; P < .00001). No statistically significant difference between the dose-response of analgesics was identified (mean difference: -1.09; 95% CI: -6.48, 4.30; P = .69). The risk of bias was assessed independently by paired evaluators.
CONCLUSION
Aprepitant effectively reduces the incidence of PONV; however, the effects of postoperative analgesia require further exploration.
Topics: Humans; Aprepitant; Postoperative Nausea and Vomiting; Ondansetron; Morpholines; Antiemetics; Vomiting; Dexamethasone
PubMed: 37478247
DOI: 10.1097/MD.0000000000034385 -
British Journal of Anaesthesia Jun 2006Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may... (Randomized Controlled Trial)
Randomized Controlled Trial Review
BACKGROUND
Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans.
METHODS
Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant.
RESULTS
Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximately 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4) degrees C, ondansetron 37.6 (0.3) degrees C, P=0.16), vasoconstriction (37.0 (0.5) degrees C vs 37.1 (0.3) degrees C; P=0.70), or shivering threshold (36.3 (0.5) degrees C vs 36.3 (0.6) degrees C; P=0.76). No sedation was observed on either study day.
CONCLUSIONS
/b>. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.
Topics: Adult; Body Temperature; Body Temperature Regulation; Dose-Response Relationship, Drug; Female; Humans; Hypothermia, Induced; Male; Ondansetron; Serotonin Antagonists; Shivering; Single-Blind Method; Skin Temperature; Sweating; Vasoconstriction
PubMed: 16675509
DOI: 10.1093/bja/ael101 -
Pain Research & Management 2024Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and delay recovery time.
METHODS
A randomized double-blinded placebo-controlled clinical trial was conducted with 80 cases of acute appendicitis of American Society of Anesthesiologists (ASA) physical status I or II and aged 18-60 y/o scheduled for appendectomy under general anesthesia. Patients were randomly divided into two equal groups: group A received 4 mg of ondansetron IV (2 ml) and group B received 2 ml of normal slain IV (placebo). Pain according to VAS, nausea and vomiting according to clinical symptoms, shivering and sedation according to the Bedside Shivering Assessment Scale (BSAS), and the Ramsay Sedation Scale (RSS) at 2, 6, 12, and 24 hours after surgery were evaluated and compared between the groups.
RESULTS
There was a significant decline in the severity of pain only at 2 hours after surgery between the ondansetron and control groups (5.3 ± 1.0 vs. 6.0 ± 1.0; =0.01), not showing a difference between the groups at 6, 12, and 24 hours after appendectomy. Postoperative nausea and vomiting at 2 (5% vs. 25%; =0.03) and 6 (7.5% vs. 27.5%; =0.04) hours after appendectomy in the ondansetron group. At different times, the ondansetron and control groups did not differ in terms of pethidine consumption or sedation.
CONCLUSIONS
In conclusion, our study found that ondansetron was effective in reducing postoperative vomiting after acute appendicitis surgery. However, it did not show a clinically significant effect on postoperative pain. This trial is registered with IRCT20230722058883N1.
Topics: Humans; Double-Blind Method; Ondansetron; Adult; Male; Female; Pain, Postoperative; Appendicitis; Young Adult; Middle Aged; Adolescent; Postoperative Nausea and Vomiting; Appendectomy; Pain Measurement; Antiemetics; Treatment Outcome; Time Factors
PubMed: 38899063
DOI: 10.1155/2024/6429874 -
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 -
Saudi Medical Journal Jul 2021To compare the efficacy of prophylactic ondansetron and tropisetron for postoperative nausea and vomiting (PONV). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To compare the efficacy of prophylactic ondansetron and tropisetron for postoperative nausea and vomiting (PONV).
METHODS
A literature search was performed to identify studies that compare the efficiency of ondansetron with that of tropisetron in preventing PONV. Only randomized controlled trials updated to January, 2021 were included.
RESULTS
The final pooled analysis included 14 studies totaling 1705 patients and indicated that ondansetron was 39% less effective than tropisetron in preventing postoperative vomiting with a higher incidence of dizziness. However, no significant difference was detected between ondansetron and tropisetron in PONV, postoperative nausea, antiemetic treatment, and headache.
CONCLUSIONS
Tropisetron is superior to ondansetron in preventing postoperative vomiting.PROSPERO No: CRD42021237368.
Topics: Antiemetics; Double-Blind Method; Humans; Ondansetron; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Tropisetron; Vomiting
PubMed: 34187913
DOI: 10.15537/smj.2021.42.7.20210135 -
Biomedical Chromatography : BMC Nov 2019Ondansetron, a widely used antiemetic agent, is a P-glycoprotein (P-gp) substrate and therefore expression of P-gp at the blood-brain barrier limits its distribution to...
Ondansetron, a widely used antiemetic agent, is a P-glycoprotein (P-gp) substrate and therefore expression of P-gp at the blood-brain barrier limits its distribution to the central nervous system (CNS), which was observed to be reversed by coadministration with P-gp inhibitors. Tariquidar is a potent and selective third-generation P-gp inhibitor, and coadministration with ondansetron has shown improved ondansetron distribution to the CNS. There is currently no reported bioanalytical method for simultaneously quantifying ondansetron with a third-generation P-gp inhibitor. Therefore, we aimed to develop and validate a method for ondansetron and tariquidar in rat and human plasma samples. A full validation was performed for both ondansetron and tariquidar, and sample stability was tested under various storage conditions. To demonstrate its utility, the method was applied to a preclinical pharmacokinetic study following coadministration of ondansetron and tariquidar in rats. The presented method will be valuable in pharmacokinetic studies of ondansetron and tariquidar in which simultaneous determination may be required. In addition, this is the first report of a bioanalytical method validated for quantification of tariquidar in plasma samples.
Topics: Animals; Chromatography, High Pressure Liquid; Humans; Limit of Detection; Linear Models; Male; Ondansetron; Quinolines; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Spectrophotometry, Ultraviolet
PubMed: 31322284
DOI: 10.1002/bmc.4653