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Anaesthesia Reports 2023Ondansetron is a highly selective 5-hydroxytryptamine receptor antagonist and the most commonly used anti-emetic for the prevention of postoperative nausea and vomiting....
Ondansetron is a highly selective 5-hydroxytryptamine receptor antagonist and the most commonly used anti-emetic for the prevention of postoperative nausea and vomiting. Ondansetron has a low affinity for dopamine receptors and so extrapyramidal side effects are rare. Here, we present the case of a 14-year-old girl who developed a severe post-operative acute dystonic reaction which included oculogyric crisis. We believe that ondansetron was the most likely cause, although propofol may have been a synergistic or alternative causative agent. The patient had no significant past medical history and had previously undergone two uneventful general anaesthetics which included both ondansetron and propofol. The prolonged duration and severity of the reaction and failure to fully respond to specific treatments resulted in the need for tracheal intubation and transfer to a paediatric intensive care unit. She subsequently recovered uneventfully with no ongoing neurological sequalae. Ondansetron-induced dystonic reactions are rare and unpredictable and can occur in patients who have previously received the drug without complication. They are thought to be caused by an imbalance between inhibitory and excitatory neurotransmitters in the extrapyramidal system. Specific treatments include anticholinergics, antihistamines and benzodiazepines.
PubMed: 37974908
DOI: 10.1002/anr3.12258 -
Anesthesia and Analgesia Jan 2024
Topics: Humans; Ondansetron; Analgesics, Opioid; Antiemetics; Morphine; Pruritus; Double-Blind Method; Anesthesia, Spinal; Injections, Spinal
PubMed: 38100800
DOI: 10.1213/ANE.0000000000006843 -
JPGN Reports Nov 2023To gather initial data on the effectiveness and tolerability of the addition of Ondansetron to bowel preparation regimens to justify a funded, larger, placebo-controlled... (Clinical Trial)
Clinical Trial
OBJECTIVES
To gather initial data on the effectiveness and tolerability of the addition of Ondansetron to bowel preparation regimens to justify a funded, larger, placebo-controlled study.
METHODS
A total of 41 pediatric and young adult (age 2-22) patients participated in a single center, open label, parallel randomized trial, with simple randomization. All patients were recruited as outpatients, and all procedures occurred as outpatient procedures, with both recruitment and procedures occurring at a low-resource urban academic medical center in Brooklyn. The intervention studied was a single dose of oral-dissolving tablet Ondansetron provided before initiation of bowel preparation using a standardized prep of Polyethylene Glycol 3350 and Bisacodyl. There were 2 arms, a study arm using typical preparation (Polyethylene Glycol 3350 and Bisacodyl) and Ondansetron, and a control arm (Polyethylene Glycol 3350 and Bisacodyl). Patients received standard weight-based dosing. The primary outcome measure assessed was the Boston Bowel Preparation Scale (BBPS) to assess efficacy of preparation. Secondary objectives included evaluation of patient satisfaction via a survey answered by each patient. The questionnaire assessed the presence of the following symptoms during bowel prep: abdominal pain, nausea, bloating, vomiting, scale of ease/difficulty, and if the entire bowel prep was completed.
RESULTS
No benefit to BBPS from the addition of Ondansetron to bowel preparation was observed. Statistically significant improvement in reports of abdominal pain (35% decrease in Ondansetron arm) was noted with a = 0.019. No statistically significant improvement was noted in other symptoms although all domains showed nonsignificant improvement in the Ondansetron arm.
CONCLUSION
No benefit to efficacy of preparation as measured by the BBPS was observed. A single dose of Ondansetron before bowel preparation reduced reports of abdominal pain by 35%, with other symptomatic improvements suggesting possible improvements to be confirmed by a higher-powered study. Trial registration: NCT05439772.
PubMed: 38034452
DOI: 10.1097/PG9.0000000000000366 -
Journal of Psychiatric Practice Sep 2023Cannabinoid hyperemesis syndrome (CHS), an under-recognized and seemingly paradoxical condition, arises in some adolescents and adults who chronically use cannabis. It...
Cannabinoid hyperemesis syndrome (CHS), an under-recognized and seemingly paradoxical condition, arises in some adolescents and adults who chronically use cannabis. It presents acutely with intractable nausea, vomiting, and abdominal pain but standard antiemetic therapy leads to improvement for only a minority of patients. Randomized controlled trial evidence in adults indicates the superiority of haloperidol over ondansetron in alleviating the acute symptoms of CHS, but safe and effective treatment for adolescents with the disorder is currently unknown. The successful use of topical capsaicin has also been reported. We report a case series of 6 adolescent patients with CHS who presented to Johns Hopkins All Children's Hospital and were treated with haloperidol, lorazepam, and/or capsaicin. Four patients given 5 mg intravenous (IV) haloperidol and 2 mg IV lorazepam and 1 patient treated with 5 mg IV haloperidol and peri-umbilical topical capsaicin (0.025%) experienced full acute symptomatic relief. One patient, treated only with topical capsaicin, reported improvement of symptoms with some persistent nausea. Haloperidol/lorazepam, haloperidol/capsaicin, and topical capsaicin alone appear safe and effective in adolescents, but larger studies are required to confirm our findings.
Topics: Adult; Child; Adolescent; Humans; Lorazepam; Haloperidol; Capsaicin; Cannabinoids; Vomiting; Nausea; Syndrome
PubMed: 37678364
DOI: 10.1097/PRA.0000000000000732 -
The European Journal of Neuroscience Mar 2024The dopaminergic system is implicated in the pathophysiology of migraine. However, the underlying mechanisms remain unclear. We explored the effects and mechanisms of...
The dopaminergic system is implicated in the pathophysiology of migraine. However, the underlying mechanisms remain unclear. We explored the effects and mechanisms of dopaminergic system modulation in the in vivo and in vitro rat models of migraine. Dopaminergic agonist apomorphine, D2 receptor antagonists metoclopramide and haloperidol and 5-HT3 receptor antagonist ondansetron alone and together were tested in nitroglycerin-induced migraine model, in vivo. Likewise, the combinations of drugs were also tested on basal calcitonin gene-related peptide (CGRP) release in vitro hemiskull preparations. Mechanical allodynia was tested by von Frey filaments. CGRP concentrations in trigeminovascular structures and in vitro superfusates and c-Fos levels in the brainstem were determined by enzyme-linked immunosorbent assay. Meningeal mast cells were evaluated with toluidine blue staining. Apomorphine further enhanced nitroglycerin-induced mechanical allodynia, brainstem c-fos expression, trigeminal ganglion and brainstem CGRP concentrations and meningeal mast cell degranulation, in vivo. Haloperidol completely antagonised all apomorphine-induced effects and also alleviated changes induced by nitroglycerin without apomorphine. Metoclopramide and ondansetron partially attenuated apomorphine- or nitroglycerin-induced effects. A combination of haloperidol and ondansetron decreased basal CGRP release, in vitro, whereas the other administrations were ineffective. Apomorphine-mediated dopaminergic activation exacerbated nitroglycerin-stimulated nociceptive reactions by further enhancing c-fos expression, CGRP release and mast cell degranulation in strategical structures associated with migraine pain. Metoclopramide partially attenuated the effects of apomorphine, most likely because it is also a 5-HT3 receptor antagonist. Haloperidol with pure D2 receptor antagonism feature appears to be more effective than metoclopramide in reducing migraine-related parameters in dopaminergic activation- and/or NTG-induced migraine-like conditions.
Topics: Rats; Animals; Hyperalgesia; Calcitonin Gene-Related Peptide; Nitroglycerin; Apomorphine; Ondansetron; Haloperidol; Metoclopramide; Receptors, Serotonin, 5-HT3; Migraine Disorders; Models, Theoretical; Receptors, Dopamine; Disease Models, Animal
PubMed: 37539658
DOI: 10.1111/ejn.16106 -
Farmacia Hospitalaria : Organo Oficial... 2023Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016... (Observational Study)
Observational Study
OBJECTIVE
Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv).
METHODS
Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out.
RESULTS
61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods.
CONCLUSIONS
Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.
Topics: Humans; Female; Middle Aged; Male; Antiemetics; Carboplatin; Anthracyclines; Nausea; Vomiting; Antibiotics, Antineoplastic; Dexamethasone; Antineoplastic Agents
PubMed: 37500396
DOI: 10.1016/j.farma.2023.06.007 -
Toxicology and Applied Pharmacology Apr 2024Cisplatin is an effective and commonly used chemotherapeutic drug; however, its use is accompanied by several adverse effects, including chemobrain. Ondansetron is a...
Cisplatin is an effective and commonly used chemotherapeutic drug; however, its use is accompanied by several adverse effects, including chemobrain. Ondansetron is a 5-HT3 antagonist, commonly used in prophylactic against chemotherapy-induced nausea and vomiting. Moreover, it has been identified as a novel neuroprotective agent in different animal models. However, its protective role against chemotherapy-induced chemobrain has not been investigated. The current study was the first study that explored the potential neuroprotective effect of ondansetron against cisplatin-induced chemobrain in rats. Cisplatin (5 mg/Kg) was injected intraperitoneally, once weekly, for 4 weeks with the daily administration of ondansetron (0.5 and 1 mg/Kg). Compared to the cisplatin-treated group, ondansetron administration showed a significant decrease in the latency time and a significant increase in ambulation, rearing, and grooming frequency in the open field test (OFT). Moreover, a significant improvement in the latency time in the rotarod and passive avoidance tests, following ondansetron administration. In addition, ondansetron treatment increased the percentage of alternation in the Y-maze test. Also, ondansetron showed a remarkable enhancement in the biochemical parameters in the hippocampus. It increased the acetylcholine (Ach) level and decreased the level of the acetylcholine esterase enzyme (AchE). Ondansetron significantly decreased interleukin-1β (Il-1β), tumor necrosis factor-alpha (TNF-α), toll-like receptor-4 (TLR-4), NOD-like receptor-3 (NLRP3) inflammasome as well as caspase-1 and caspase-3 levels. Furthermore, ondansetron significantly decreased the levels of copper transporter-1(CTR1) expression in the hippocampus. Collectively, these findings suggest that ondansetron may exhibit a neuroprotective and therapeutic activity against cisplatin-induced chemobrain.
Topics: Animals; Ondansetron; Cisplatin; Male; Inflammasomes; Behavior, Animal; Rats; Down-Regulation; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Wistar; Hippocampus; Antineoplastic Agents; Signal Transduction; Serotonin 5-HT3 Receptor Antagonists; Chemotherapy-Related Cognitive Impairment
PubMed: 38437957
DOI: 10.1016/j.taap.2024.116875 -
Clinical Pharmacology and Therapeutics Oct 2023The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and...
The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, i.v. fluid, and topical products and over-the-counter medications, the proportion of women that reported taking at least one prescription medication in the first trimester increased over the study years, from 37% to 50% of women. The corresponding proportions increased with increasing maternal age and years of education, were highest for non-Hispanic White women (47%) and lowest for Hispanic women (24%). The most common indication for first trimester use of a medication was infection (12-15%). Increases were observed across the years for medications used for indications related to nausea/vomiting, depression/anxiety, infertility, thyroid disease, diabetes, and epilepsy. The largest relative increase in use among women was observed for medications to treat nausea/vomiting, which increased from 3.8% in the earliest years of the study (1997-2001) to 14.8% in 2014-2018, driven in large part by ondansetron use. Prescription medication use in the first trimester of pregnancy is common and increasing. Many medical conditions require treatments among pregnant women, often involving pharmacotherapy, which necessitates consideration of the risk and safety profiles for both mother and fetus.
Topics: Pregnancy; Female; Humans; United States; Pregnancy Trimester, First; Prescription Drugs; Prescriptions; Nausea; Vomiting
PubMed: 37356083
DOI: 10.1002/cpt.2981 -
Journal of Anesthesia Jun 2024To investigate the association between adherence to guideline-recommended risk-based postoperative nausea and vomiting (PONV) prophylaxis, the antiemetics used for PONV... (Comparative Study)
Comparative Study
Comparison of prophylaxis strategy for postoperative nausea and vomiting and its incidence before and after the implementation of 5-hydroxytryptamine 3 in surgical setting: a single-center, retrospective study.
PURPOSE
To investigate the association between adherence to guideline-recommended risk-based postoperative nausea and vomiting (PONV) prophylaxis, the antiemetics used for PONV prophylaxis, and the incidence of PONV in patients who were underwent general anesthesia before and after 5-HT3 receptor antagonists became available.
METHODS
Patients (≥ 20 years old) who were extubated after scheduled surgery and returned to general wards between January 2021 and February 2022 and between June 2022 and July 2023 were included. Risk factors included age < 50, female, motion sickness, nonsmoker, surgical factors, and postoperative opioid use. Two and three or more prophylaxis were recommended for patients with one or two and three or more risk factors, respectively. The primary outcome was the number of patients who received adequate prophylaxis, and the secondary outcomes were antiemetic agents used during anesthesia and the incidence of PONV on postoperative days 0 and 1. PONV was defined as documented PONV or rescue antiemetic administration.
RESULTS
From January 2021 to February 2022 and from June 2022 to July 2023, 2342 and 2682 patients were included, respectively. Before ondansetron became available, more D2 receptor antagonists were used (p < 0.001), and after ondansetron became available, both ondansetron (p < 0.001) and propofol (p < 0.001) were given more frequently. Before and after ondansetron became available, the number of patients with adequate prophylaxis was 3.7% and 9.2%, respectively (p < 0.001), and the incidence of PONV on postoperative days 0 and 1 was 44.6% and 44.0%, respectively (p = 0.67).
CONCLUSION
The availability of ondansetron increased the number of patients with adequate PONV prophylaxis, but did not decrease the incidence of PONV.
Topics: Humans; Postoperative Nausea and Vomiting; Female; Male; Antiemetics; Incidence; Retrospective Studies; Middle Aged; Serotonin 5-HT3 Receptor Antagonists; Anesthesia, General; Adult; Ondansetron; Risk Factors; Aged
PubMed: 38436772
DOI: 10.1007/s00540-024-03327-3 -
Pharmaceuticals (Basel, Switzerland) Dec 2023Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is...
INTRODUCTION
Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is mainly metabolized in the liver, and it might accumulate in patients with hepatic impairment and lead to unwanted adverse events.
METHODS
A physiologically based pharmacokinetic (PBPK) model was developed to predict the exposure of ondansetron in healthy and liver cirrhosis populations. The population-based PBPK simulator PK-Sim was utilized for simulating ondansetron exposure in healthy and liver cirrhosis populations.
RESULTS
The developed model successfully described the pharmacokinetics of ondansetron in healthy and liver cirrhosis populations. The predicted area under the curve, maximum systemic concentration, and clearance were within the allowed twofold range. The exposure of ondansetron in the population of Child-Pugh class C has doubled in comparison to Child-Pugh class A. The dose has to be adjusted for liver cirrhosis patients to ensure comparable exposure to a healthy population.
CONCLUSION
In this study, the developed PBPK model has described the pharmacokinetics of ondansetron successfully. The PBPK model has been successfully evaluated to be used as a tool for dose adjustments in liver cirrhosis patients.
PubMed: 38139819
DOI: 10.3390/ph16121693