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Drug Design, Development and Therapy 2024Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the... (Randomized Controlled Trial)
Randomized Controlled Trial
Dose-Response Study of Phenylephrine for Preventing Spinal-Induced Hypotension During Cesarean Delivery with Combined Spinal-Epidural Anesthesia Under the Effect of Prophylactic Intravenous Ondansetron.
BACKGROUND
Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method.
METHODS
A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 μg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis.
RESULTS
The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) μg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups.
CONCLUSION
The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) μg/kg/min for phenylephrine to prevent SIH.
Topics: Adult; Female; Humans; Pregnancy; Anesthesia, Epidural; Anesthesia, Spinal; Cesarean Section; Dose-Response Relationship, Drug; Hypotension; Ondansetron; Phenylephrine
PubMed: 38707613
DOI: 10.2147/DDDT.S452983 -
Frontiers in Endocrinology 2024The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea... (Clinical Trial)
Clinical Trial
The prophylactic antiemetic therapies in management of differentiated thyroid cancer patients with radioactive iodine therapy: a single-center, non-randomized clinical trial.
OBJECTIVE
The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy.
METHOD
We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases.
RESULTS
A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders.
CONCLUSIONS
In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.
Topics: Humans; Male; Female; Middle Aged; Antiemetics; Adult; Iodine Radioisotopes; Aged; Vomiting; Nausea; Young Adult; Adolescent; Thyroid Neoplasms; Ondansetron; Quality of Life
PubMed: 38706697
DOI: 10.3389/fendo.2024.1310223 -
Ugeskrift For Laeger Apr 2024Evidence suggests that available antiemetics are equal to intravenous fluid treatment against acute nausea of other causes than motion sickness, pregnancy, anaesthesia,... (Review)
Review
Evidence suggests that available antiemetics are equal to intravenous fluid treatment against acute nausea of other causes than motion sickness, pregnancy, anaesthesia, chemo- or radiation therapy. Each antiemetic is associated with adverse effects, which include movement disorders, sedation, and QT prolongation. Intravenous fluid and treatment directed against underlying pathology is recommended as a first-line treatment against nausea in these patients. If an antiemetic is clinically warranted, ondansetron has the most favourable ratio between side effects and price, as argued in this review.
Topics: Humans; Antiemetics; Nausea; Acute Disease; Ondansetron; Fluid Therapy; Hospitalization; Female; Pregnancy
PubMed: 38704720
DOI: 10.61409/V11230735 -
Scientific Reports Apr 2024Lung cancer, a global mortality leader, often necessitates Video-Assisted Thoracoscopic (VATS) surgery. However, post-operative nausea and vomiting (PONV) is common,... (Comparative Study)
Comparative Study
Lung cancer, a global mortality leader, often necessitates Video-Assisted Thoracoscopic (VATS) surgery. However, post-operative nausea and vomiting (PONV) is common, highlighting a need for effective management and prevention strategies in this context. A retrospective case-control study at Fujian Medical University Union Hospital evaluated patients undergoing VATS radical resection of lung cancer between May and September 2022. Patients were categorized based on PONV prevention methods, and data encompassing demographics, surgical history, and postoperative adverse events s were analyzed to assess the association between prophylactic protocols and PONV incidence. The Netupitant and Palonosetron Hydrochloride (NEPA) group showed a significant reduction in PONV occurrences post-surgery compared to Ondansetron (ONDA) and Control groups, emphasizing NEPA's efficacy in alleviating PONV symptoms (P < 0.05). Furthermore, following VATS radical resection of lung cancer, NEPA markedly reduced the intensity of PONV symptoms in patients. Both univariate and multivariate logistic analyses corroborated that NEPA independently reduces PONV risk, with its protective effect also apparent in susceptible populations like females and non-smokers. NEPA utilization markedly reduced both the incidence and severity of PONV in patients undergoing VATS radical resection of lung cancer, serving as an independent protective factor in mitigating PONV risk post-surgery.
Topics: Humans; Female; Thoracic Surgery, Video-Assisted; Male; Lung Neoplasms; Postoperative Nausea and Vomiting; Middle Aged; Retrospective Studies; Aged; Case-Control Studies; Antiemetics; Ondansetron; Palonosetron
PubMed: 38684769
DOI: 10.1038/s41598-024-59687-z -
Neuropharmacology Aug 2024This research aims to investigate the possible antiallodynic and antihyperalgesic effects of pure vitexin and vitexin-loaded solid lipid nanoparticles (SLN) on...
This research aims to investigate the possible antiallodynic and antihyperalgesic effects of pure vitexin and vitexin-loaded solid lipid nanoparticles (SLN) on neuropathic pain and the pathways mediating these effects. Chronic constriction nerve injury was induced in female rats, and the effects of vitexin at the doses of 5, 10, 20, 40 mg/kg were evaluated. Ketanserin, ondansetron, WAY-100635, yohimbine and bicuculin, which are antagonists of receptors on pain pathways. were used to examine the mechanisms of the effects of vitexin. Pure vitexin exhibited antiallodynic activity at all administered doses, whereas antihyperalgesic activity was not observed at 5 mg/kg vitexin dose. SLN formulation was prepared with 5 mg/kg vitexin, the lowest dose. Vitexin-loaded formulation significantly increased antiallodynic and antihyperalgesic effects. Ondansetron, WAY-100635, yohimbine, and bicuculine antagonized the antiallodynic and antihyperalgesic effects of vitexin. So, it was concluded that serotonin (5-hydroxtryptamine, 5-HT) receptor subtypes 5-HT3 and 5-HT1A, alpha-2 adrenergic, and γ-Aminobutyric acid type A (GABA-A) receptors are involved in the antiallodynic and antihyperalgesic activity of vitexin. In conclusion, vitexin and vitexin-loaded formulation have the potential for clinical use in neuropathic pain management, and different pain pathways contributed to this effect. And also, it is thought that vitexin-loaded SLN formulation is more effective than pure vitexin, which will provide an advantage in treatment.
Topics: Animals; Neuralgia; Apigenin; Female; Nanoparticles; Analgesics; Rats; Hyperalgesia; Dose-Response Relationship, Drug; Rats, Wistar; Disease Models, Animal; Lipids; Liposomes
PubMed: 38657947
DOI: 10.1016/j.neuropharm.2024.109961 -
Autonomic Neuroscience : Basic &... Jun 2024Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT receptors involves...
PURPOSE
Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT receptors involves impairment of intestinal functions. This study aimed to investigate the effects of ondansetron, a 5-HT receptor antagonist, on locomotor activity, anxiety-related behaviors, and colonic functions in repeated water avoidance stress.
MATERIALS AND METHODS
Food intake and fecal pellet output (FPO) of sham stress (SS), water avoidance stress (WS), and water avoidance stress with oral administration of ondansetron (1 mg/kg BW) (WA) groups were monitored along the water avoidance stress protocol for 10 consecutive days. On day 11, locomotor activity and anxiety-related behaviors were determined using an open field test. Contractile properties of colonic tissues in response to KCl and a cumulative dose of carbachol (CCh) were determined using in vitro organ bath technique.
RESULTS
FPO was significantly increased in the WS group after 7 days of water avoidance stress, which was reversed in WA group. WS group decreased unsupported rearing behavior compared to WS group, which was not altered in the WA group. The colon of the WS group had a higher tonic contraction in response to CCh than the SS and WA groups, which was reversed with ondansetron pre-incubation.
CONCLUSIONS
Oral administration of ondansetron prevented increased FPO but did not affect anxiety-related behavior in repeated stress model. Colonic hypercontractility in the stressed mice was related to increased responses to cholinergic-induced contractions, which involved 5-HT receptors. Our findings suggest the modulatory roles of 5-HT receptors to mediate stress-induced colonic dysfunction.
Topics: Animals; Ondansetron; Stress, Psychological; Male; Serotonin 5-HT3 Receptor Antagonists; Colon; Administration, Oral; Mice; Anxiety; Disease Models, Animal; Muscle Contraction; Eating
PubMed: 38642511
DOI: 10.1016/j.autneu.2024.103178 -
Psychopharmacology Apr 2024Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of...
RATIONALE
Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects.
OBJECTIVE
To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CFSePB) in mice and the involvement of the serotonergic and noradrenergic systems.
METHODS
Male Swiss mice were treated with CFSePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CFSePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT receptor antagonist), prazosin (1 mg/kg, i.p., an α-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CFSePB (50 mg/kg, i.g.), and after 30 min of CFSePB administration the FST was performed.
RESULTS
CFSePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT and 5-HT receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CFSePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice.
CONCLUSION
This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.
PubMed: 38635075
DOI: 10.1007/s00213-024-06588-8 -
Cirugia Pediatrica : Organo Oficial de... Apr 2024Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce.
Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis.
BACKGROUND
Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce.
MATERIALS AND METHODS
We prospectively compared the analgesic and emetogenic profile of intravenous ibuprofen and metamizole in the immediate postoperative period of PAA. For this purpose, we used a sample of patients operated on in 2021 in our center. Participants were recruited on arrival at the Emergency Department and histopathological confirmation of the diagnosis was obtained in all of them. Pain was evaluated every 8 hours after the surgery with validated visual analog scales ranging from 0 to 10 points. Repeated measures ANOVA was used to compare the evolution of pain in the 48 hours after surgery between the two groups.
RESULTS
The sample included 95 patients (65% males) with a mean age of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen (group 1) and 54 with metamizole (group 2). No significant differences were found in the level of pain either in the comparisons of point measurements or in its evolution in the 48 hours after surgery (p= 0.58). After adjusting for the received fluid therapy, children in the metamizole group had significantly more emetic episodes and needed significantly more doses of ondansetron.
CONCLUSIONS
In our cohort, ibuprofen had a similar analgesic efficacy and a better emetogenic profile than metamizole in the immediate postoperative period of PAA. Future prospective, adequately controlled studies with larger sample sizes are needed to validate these findings.
Topics: Male; Humans; Child; Female; Ibuprofen; Dipyrone; Appendicitis; Pain, Postoperative; Analgesics; Postoperative Period
PubMed: 38623799
DOI: 10.54847/cp.2024.02.15 -
International Journal of Emergency... Apr 2024Ondansetron is one of the most commonly used drugs in the emergency department (ED) for treating nausea and vomiting, particularly in intravenous (IV) form....
BACKGROUND
Ondansetron is one of the most commonly used drugs in the emergency department (ED) for treating nausea and vomiting, particularly in intravenous (IV) form. Nevertheless, it has been shown to prolong QT interval and increase the risk of ventricular dysrhythmias. This study evaluated the associations between single IV ondansetron dosage and subsequent QTc prolongation in the ED.
METHODS
In this prospective observational study, a total number of 106 patients presenting to the ED in a 3-month period with nausea and vomiting treated with IV ondansetron were enrolled. QT and QTc intervals were measured at baseline (QT0 and QTc0), and 60 min (QT60 and QTc60) following a single-dose administration of ondansetron at 4 or 8 mg doses. To evaluate the predictive ability of these variables, we employed receiver operating characteristic (ROC) curve analyses.
RESULTS
The predictive models for QTc prolongation 1-hour post-ondansetron administration showed the following: at baseline, the area under curve of 0.70 for QT, 0.71 for QTc, and 0.64 for dosage. Conversely, a QTc0 = 375 msec indicated a QTc60 > 480 msec with a specificity of 97%. Additionally, a QTc0 of 400 msec had a sensitivity of 100% in predicting a QTc60 < 480 msec, while a QTc0 > 460 msec predicted a QTc60 > 480 msec with a specificity of 98%. Moreover, 8 mg doses were associated with higher rates of QTc60 prolongation, while 4 mg doses favored maintaining QTc60 within normal limits.
CONCLUSIONS
Our study demonstrates the predictive capacity of QT0, QTc0, and ondansetron dosage in forecasting QTc60 prolongation (> 480 msec) post-ondansetron administration. These findings advocate for their incorporation into clinical protocols to enhance safety monitoring in adult ED patients.
PubMed: 38566008
DOI: 10.1186/s12245-024-00621-5 -
International Review of Neurobiology 2024Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in... (Review)
Review
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.
Topics: Humans; Alcoholism; Acamprosate; Naltrexone; Disulfiram; Sodium Oxybate; Baclofen; Drug Repositioning; Substance Withdrawal Syndrome; Alcohol Drinking
PubMed: 38555115
DOI: 10.1016/bs.irn.2024.02.002