RESUMEN
PURPOSE: Serotonin (5-HT3) receptor antagonists are promising agents for treatment of neuropathic pain. However, insufficient drug exposure at the central nervous system (CNS) might result in lack of efficacy. The goal of this study was to evaluate the impact of administration of a Pgp inhibitor (tariquidar) on ondansetron exposure in the brain, spinal cord, and cerebrospinal fluid in a wild-type rat model. METHODS: Ondansetron (10 mg/kg) and tariquidar (7.5 mg/kg) were administered intravenously, plasma and tissue samples were collected and analyzed by HPLC. A mathematical model with brain, spinal cord, cerebrospinal fluid and two systemic disposition compartments was developed to describe the data. RESULTS: The results demonstrate that tariquidar at 7.5 mg/kg resulted in a complete inhibition of Pgp efflux of ondansetron in the brain and spinal cord. The compartmental model successfully captured pharmacokinetics of ondansetron in wild type and Pgp knockout (KO) animals receiving the drug alone or in wild type animals receiving the ondansetron and tariquidar combination. CONCLUSIONS: The study provided important quantitative information on enhancement of CNS exposure to ondansetron using co-administration of Pgp Inhibitor in a rat model, which will be further utilized in conducting a clinical study. Tariquidar co-administration resulted in ondansetron CNS exposure comparable to observed in Pgp KO rats. Results also highlighted the effect of tariquidar on plasma disposition of ondansetron, which may not be dependent on Pgp inhibition, and should be evaluated in future studies.
Asunto(s)
Ondansetrón , Quinolinas , Médula Espinal , Animales , Ondansetrón/farmacocinética , Ratas , Masculino , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Quinolinas/farmacocinética , Quinolinas/administración & dosificación , Ratas Sprague-Dawley , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Modelos Biológicos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/efectos de los fármacos , Antagonistas del Receptor de Serotonina 5-HT3/farmacocinética , Antagonistas del Receptor de Serotonina 5-HT3/farmacologíaRESUMEN
INTRODUCTION: Selective 5-hydroxytryptamine 3 receptor (5-HT3) antagonists are commonly used to prevent nausea and vomiting (NV) after cesarean section, but the comparative efficacy of different 5-HT3 antagonists remains unclear. This network meta-analysis aimed to determine which 5-HT3 antagonists might be the preferred choice for preventing NV in parturient scheduled for elective cesarean delivery under spinal anesthesia. EVIDENCE ACQUISITION: PubMed, EMBASE, Cochrane library, and Web of Science were searched for relevant randomized controlled trials (RCTs) published before August 24, 2023. Random network meta-analysis was performed using Stata 14.0 to estimate the efficacy of different 5-HT3 antagonists in preventing intra- and post-operative NV. EVIDENCE SYNTHESIS: Twenty-eight studies involving seven dosing regimens of three 5-HT3 antagonists were included. Pooled results showed that ondansetron 12 mg was superior to other six dosing regimens in the prevention of postoperative NV (PONV), PON, and POV, with the ranking probability of 80.2%, 95.8%, and 87.7%, respectively, followed by granisetron two mg. Ondansetron 4 mg might be the first choice for preventing intraoperative NV (IONV) (92.8%), with the least use of postoperative rescue antiemetics (90.6%). Granisetron 3 mg and tropisetron 2 mg might be the best options for preventing ION and IOV, respectively. CONCLUSIONS: Based on available data, ondansetron 12 mg may have the best efficacy in preventing PONV, PON, and POV. Additionally, more studies are warranted to compare the safety of ondansetron 12 mg versus granisetron two mg.
Asunto(s)
Antieméticos , Cesárea , Náusea y Vómito Posoperatorios , Antagonistas del Receptor de Serotonina 5-HT3 , Femenino , Humanos , Embarazo , Antieméticos/uso terapéutico , Metaanálisis en Red , Ondansetrón/uso terapéutico , Náusea y Vómito Posoperatorios/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéuticoRESUMEN
BACKGROUND: Inhibition of 5-HT3 (5-Hydroxyl Tryptamine) receptors is known to enhance morphine analgesia in animal models. We tested the efficacy of azasetron, a 5-HT3 receptor antagonist, on postoperative chronic pain after pulmonary surgery in a randomized triple-blind controlled study. METHODS: A total of 250 patients who were scheduled to receive pulmonary surgery were randomized to patient-controlled analgesia (PCA) using 200 µg sufentanil with normal saline or 200 µg sufentanil with 20 mg azasetron. The numerical rating scale of pain (NRS) was recorded at baseline, postoperative day (POD) 1, 2, 3, 90, and 180. Negative binomial regression was used to identify associated factors for postoperative NRS six months after surgery. RESULTS: The results showed that azasetron did not affect the primary outcomes: the incidence of postoperative chronic pain on POD90 and 180. However, azasetron decreased postoperative NRS at rest and activity on POD1, 2, and 3. Furthermore, azasetron decreased postoperative nausea and vomiting on POD1 and 2. Univariate and multivariate negative binomial regression analysis identified preoperative pain, smoking, drinking and open surgery are risk factors of chronic pain six months after surgery. CONCLUSIONS: Azasetron did not affect the incidence of chronic pain after pulmonary surgery. The presence of preoperative pain, smoking, drinking, and open surgery were found to be associated with chronic pain six months after surgery. CLINICAL TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200060139), 20/05/2022; the site url is https://www.chictr.org.cn/ .
Asunto(s)
Analgesia Controlada por el Paciente , Benzamidas , Dolor Crónico , Oxazinas , Dolor Postoperatorio , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Benzamidas/uso terapéutico , Benzamidas/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/prevención & control , Método Doble Ciego , Pulmón/cirugía , Oxazinas/administración & dosificación , Oxazinas/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Antagonistas del Receptor de Serotonina 5-HT3/administración & dosificación , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéuticoRESUMEN
Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT3RA) for the first 3 days. The daily administration of 5-HT3RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT3RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT3RA) and resuming 5-HT3RA group (patients who resumed 5-HT3RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT3RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT3RA group following the resumption of 5-HT3RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT3RA according to the condition of each patient.
Asunto(s)
Glioma , Náusea , Antagonistas del Receptor de Serotonina 5-HT3 , Temozolomida , Vómitos , Humanos , Temozolomida/uso terapéutico , Temozolomida/administración & dosificación , Temozolomida/efectos adversos , Masculino , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Antagonistas del Receptor de Serotonina 5-HT3/administración & dosificación , Femenino , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Persona de Mediana Edad , Glioma/tratamiento farmacológico , Glioma/radioterapia , Factores de Riesgo , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Adulto , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/administración & dosificación , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodosRESUMEN
The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG). Lycopene (intraperitoneal; i.p.) was administered alone or in combination with 5-HT3 receptor antagonist ondansetron (i.p.) or IDO1 inhibitor minocycline (i.p.), and the behavioral screening was performed by the sucrose preference test, open field test, tail suspension test, and splash test which are based on the different principles. Further, the brains were subjected to the biochemical analysis of serotonin and its precursor tryptophan by the HPLC. The results showed depression-like behavior in BCG-inoculated mice, which was reversed by lycopene administration. Moreover, prior treatment with ondansetron or minocycline potentiated the antidepressant action of lycopene. Minocycline pretreatment also enhanced the antidepressant effect of ondansetron indicating the regulation of IDO1 activity by 5-HT3 receptor-triggered signaling. Biochemical analysis of brain samples revealed a drastic reduction in the levels of tryptophan and serotonin in depressed animals, which were restored following treatment with lycopene and its combination with ondansetron or minocycline. Taken together, the data from molecular docking, behavioral experiments, and biochemical estimation suggest that lycopene might block the 5-HT3 receptor and consequently inhibit the activity of IDO1 to ameliorate BCG-induced depression in mice.
Asunto(s)
Encéfalo , Depresión , Indolamina-Pirrol 2,3,-Dioxigenasa , Licopeno , Receptores de Serotonina 5-HT3 , Animales , Licopeno/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Ratones , Depresión/tratamiento farmacológico , Depresión/metabolismo , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Receptores de Serotonina 5-HT3/metabolismo , Fenotipo , Simulación del Acoplamiento Molecular , Serotonina/metabolismo , Vacuna BCG/farmacología , Ondansetrón/farmacología , Conducta Animal/efectos de los fármacos , Antagonistas del Receptor de Serotonina 5-HT3/farmacología , Antidepresivos/farmacología , Minociclina/farmacologíaAsunto(s)
Anestesiólogos , Cesárea , Antagonistas del Receptor de Serotonina 5-HT3 , Humanos , Embarazo , Femenino , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Náusea y Vómito Posoperatorios/prevención & control , Antieméticos/uso terapéutico , Náusea/prevención & control , Náusea/etiología , Náusea/tratamiento farmacológicoRESUMEN
BACKGROUND: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting. METHODS: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied. RESULTS: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013). CONCLUSIONS: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis.
Asunto(s)
Acetaminofén , Analgésicos no Narcóticos , Analgésicos Opioides , Dolor Postoperatorio , Sistema de Registros , Antagonistas del Receptor de Serotonina 5-HT3 , Humanos , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Masculino , Femenino , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Persona de Mediana Edad , Antagonistas del Receptor de Serotonina 5-HT3/administración & dosificación , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Adulto , Anciano , Quimioterapia Combinada , Interacciones Farmacológicas/fisiologíaRESUMEN
BACKGROUND: Dopamine antagonists, 5-HT3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery. METHODS: We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes. RESULTS: A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT3 antagonists, dopamine antagonists, dexamethasone, and 5-HT3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low. CONCLUSIONS: Combined 5-HT3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023454602.
Asunto(s)
Antieméticos , Cesárea , Dexametasona , Morfina , Metaanálisis en Red , Náusea y Vómito Posoperatorios , Humanos , Náusea y Vómito Posoperatorios/prevención & control , Morfina/administración & dosificación , Morfina/uso terapéutico , Femenino , Antieméticos/uso terapéutico , Antieméticos/administración & dosificación , Cesárea/efectos adversos , Embarazo , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Antagonistas de Dopamina/uso terapéutico , Antagonistas de Dopamina/administración & dosificación , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: There has been a lack of research comparing the efficacy of various treatments for low anterior resection syndrome (LARS). METHODS: We conducted a comprehensive search across six electronic databases and a paired meta-analysis was undertaken to assess the effectiveness of the interventions. Furthermore, a network meta-analysis was utilized to compare the efficacy of different treatments for LARS. RESULTS: This study encompassed nine randomized controlled trials, involving a total of 450 patients. Compared to routine care, 5-HT3 receptor antagonists (follow-up<3 months) and percutaneous tibial nerve stimulation (3 months ≤ follow-up <6 months) were effective in reducing the LARS score. Pelvic floor rehabilitation (follow-up≤3 months) was effective in decreasing daily number of bowel movements when compared to routine care. The network meta-analysis indicated that 5-HT3 receptor antagonists (follow-up<3 months) were the most effective in reducing both the LARS score and the daily number of bowel movements. Transanal irrigation (3 months ≤ follow-up ≤ 12 months) was most effective in reducing the LARS score. Additionally, 5-HT3 receptor antagonists demonstrated relative efficacy in improving patients' quality of life (follow-up ≤ 1 month). CONCLUSIONS: This review indicates that 5-HT3 receptor antagonists and anal irrigation show significant promise in the treatment of LARS. Nevertheless, the contributions of percutaneous tibial nerve stimulation and pelvic floor rehabilitation to LARS treatment should not be overlooked. Given the clinical heterogeneity observed among the studies, the results should be interpreted with caution.
Asunto(s)
Metaanálisis en Red , Proctectomía , Humanos , Diafragma Pélvico , Complicaciones Posoperatorias/rehabilitación , Complicaciones Posoperatorias/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/cirugía , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Nervio Tibial , Estimulación Eléctrica Transcutánea del Nervio/métodosRESUMEN
PURPOSE: Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT3 receptors involves impairment of intestinal functions. This study aimed to investigate the effects of ondansetron, a 5-HT3 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-HT3 receptors. Our findings suggest the modulatory roles of 5-HT3 receptors to mediate stress-induced colonic dysfunction.
Asunto(s)
Ansiedad , Colon , Ondansetrón , Antagonistas del Receptor de Serotonina 5-HT3 , Estrés Psicológico , Animales , Ondansetrón/farmacología , Ondansetrón/administración & dosificación , Estrés Psicológico/fisiopatología , Masculino , Antagonistas del Receptor de Serotonina 5-HT3/farmacología , Antagonistas del Receptor de Serotonina 5-HT3/administración & dosificación , Colon/efectos de los fármacos , Colon/fisiopatología , Administración Oral , Ratones , Ansiedad/fisiopatología , Ansiedad/tratamiento farmacológico , Modelos Animales de Enfermedad , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiologíaRESUMEN
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-1ß (Il-1ß), 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.
Asunto(s)
Conducta Animal , Cisplatino , Inflamasomas , Ondansetrón , Animales , Ondansetrón/farmacología , Cisplatino/toxicidad , Masculino , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Ratas , Regulación hacia Abajo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Wistar , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Antineoplásicos/toxicidad , Transducción de Señal/efectos de los fármacos , Antagonistas del Receptor de Serotonina 5-HT3/farmacología , Deterioro Cognitivo Relacionado con la Quimioterapia/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Anestesia General , Antieméticos , Náusea y Vómito Posoperatorios , Antagonistas del Receptor de Serotonina 5-HT3 , Humanos , Náusea y Vómito Posoperatorios/prevención & control , Náusea y Vómito Posoperatorios/epidemiología , Femenino , Masculino , Antieméticos/uso terapéutico , Antieméticos/administración & dosificación , Incidencia , Estudios Retrospectivos , Persona de Mediana Edad , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Anestesia General/métodos , Anestesia General/efectos adversos , Adulto , Ondansetrón/uso terapéutico , Factores de Riesgo , AncianoRESUMEN
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients. METHODS: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias. RESULTS: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively). CONCLUSION: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients.
Asunto(s)
Antieméticos , Antineoplásicos , Humanos , Niño , Palonosetrón/uso terapéutico , Isoquinolinas/uso terapéutico , Quinuclidinas/uso terapéutico , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/tratamiento farmacológico , Antieméticos/uso terapéutico , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéuticoRESUMEN
Nicotine abuse is frequent worldwide leading to about 8 millions people die every year due to tobacco related diseases. Military personnel often use nicotine smoking that is about 12.8% higher than civilian populations. Nicotine smoking triggers oxidative stress and are linked to several neurodegenerative diseases such as Alzheimer's disease. Nicotine neurotoxicity induces significant depression and oxidative stress in the brain leading to neurovascular damages and brain pathology. Thus, details of nicotine neurotoxicity and factors influencing them require additional investigations. In this review, effects of engineered nanoparticles from metals Ag and Cu (50-60 nm) on nicotine neurotoxicity are discussed with regard to nicotine smoking. Military personnel often work in the environment where chances of nanoparticles exposure are quite common. In our earlier studies, we have shown that nanoparticles alone induces breakdown of the blood-brain barrier (BBB) and exacerbates brain pathology in animal models. In present investigation, nicotine exposure in with Ag or Cu nanoparticles intoxicated group exacerbated BBB breakdown, induce oxidative stress and aggravate brain pathology. Treatment with nanowired H-290/51 a potent chain-breaking antioxidant together with nanowired ondansetron, a potent 5-HT3 receptor antagonist significantly reduced oxidative stress, BBB breakdown and brain pathology in nicotine exposure associated with Ag or Cu nanoparticles intoxication. The functional significance of this findings and possible mechanisms of nicotine neurotoxicity are discussed based on current literature.
Asunto(s)
Edema Encefálico , Nanopartículas , Fármacos Neuroprotectores , Animales , Humanos , Ondansetrón/farmacología , Antioxidantes/farmacología , Antagonistas del Receptor de Serotonina 5-HT3/farmacología , Nicotina/farmacología , Neuroprotección , Fármacos Neuroprotectores/farmacología , EncéfaloRESUMEN
PURPOSE: Nausea is a common and unpleasant sensation for which current therapies such as serotonin (5-HT3) antagonists are often ineffective, while also conferring a risk of potential adverse events. Isopropyl alcohol (IPA) has been proposed as a treatment for nausea. We aimed to compare IPA with 5-HT3 antagonists for the treatment of nausea across all clinical settings. METHODS: MEDLINE, EMBASE, PubMed, CENTRAL and CINAHL were searched from inception to 17 July 2023 for randomised controlled trials (RCTs) comparing inhaled IPA and a 5-HT3 antagonist for treatment of nausea. Severity and duration of nausea, rescue antiemetic use, adverse events and patient satisfaction were the outcomes sought. Risk of bias (RoB) was assessed using Cochrane RoB 2. Random-effects model was used for meta-analysis. Combination of meta-analyses and narrative review was used to synthesise findings. The evidence was appraised using GRADE. RESULTS: From 1242 records, 4 RCTs were included with 382 participants. Participants receiving IPA had a significantly lower mean time to 50% reduction in nausea (MD - 20.06; 95% CI - 26.26, - 13.85). Nausea score reduction at 30 min was significantly greater in the IPA group (MD 21.47; 95% CI 15.47, 27.47). IPA led to significantly reduced requirement for rescue antiemetics (OR 0.60; 95% CI 0.37, 0.95; p = 0.03). IPA led to no significant difference in patient satisfaction when compared with a 5-HT3 antagonist. The overall GRADE assessment of evidence quality ranged from very low to low. CONCLUSION: IPA may provide rapid, effective relief of nausea when compared with 5-HT3 antagonists.
Asunto(s)
Antieméticos , Serotonina , Humanos , Serotonina/uso terapéutico , 2-Propanol/uso terapéutico , Náusea/tratamiento farmacológico , Náusea/inducido químicamente , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéuticoRESUMEN
5-HT3 receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in chemotherapy patients. However, current and previous studies reveal novel potentials of those ligands in other diseases involving the nervous system, such as addiction, pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and cognitive function. This review gathers existing studies to support the role of 5-HT3 receptors in CIPN modulation. It has been reported that chemotherapy drugs increase the 5-HT content that binds with the 5-HT3 receptor, which later induces pain. As also shown in pre-clinical and clinical studies that various neuropathic pains could be blocked by the 5-HT3 receptor antagonists, we proposed that 5-HT3 receptor antagonists via 5- HT3 receptors may also inhibit neuropathic pain induced by chemotherapy. Our review suggests that future studies focus more on the 5-HT3 receptor antagonists and their modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related pain.
Asunto(s)
Antineoplásicos , Enfermedades del Sistema Nervioso Periférico , Humanos , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/metabolismo , Serotonina/efectos adversos , Antagonistas del Receptor de Serotonina 5-HT3/efectos adversos , Antineoplásicos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/prevención & controlRESUMEN
As an antiemetic, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist (ramosetron) is generally administered to prevent and treat postoperative nausea and vomiting induced by intravenous dezocine for patient-controlled analgesia. To date, the physicochemical stability of dezocine-ramosetron admixtures has not been assessed. The primary objective of this study was to evaluate the physicochemical stability of a combination of dezocine and ramosetron in 0.9% sodium chloride (normal saline [NS]) injections. Dezocine-ramosetron admixtures were prepared and stored in glass bottles and polyvinyl chloride (PVC) bags refrigerated at 4°C or stored at ambient temperatures (25°C) for up to 14 days. Initial concentrations were 5.0 mg/100 mL for dezocine and 0.3 mg/100 mL for ramosetron used as the diluents. Stability parameters (drug concentrations and pH values) were determined using high-performance liquid chromatography and pH measurements, respectively. Compatibility (cloudiness, discoloration, and precipitation) was assessed visually. After 14 days at 4 °C or 25 °C, the concentration losses of dezocine and ramosetron were both < 4%. Furthermore, there were no significant changes in color, turbidity, or pH values were observed in any of the batches. The results indicated that mixtures of dezocine and ramosetron in NS injections were continuously physically and chemically stable for 14 days in glass bottles or PVC bags stored at 4 °C or 25 °C.
Asunto(s)
Analgesia Controlada por el Paciente , Cloruro de Sodio , Humanos , Analgesia Controlada por el Paciente/métodos , Estabilidad de Medicamentos , Cloruro de Polivinilo , Antagonistas del Receptor de Serotonina 5-HT3/químicaRESUMEN
Pain in Parkinson's disease (PD) is increasingly recognized as a major factor associated with poor life quality of PD patients. However, classic therapeutic drugs supplying dopamine have limited therapeutic effects on PD-related pain. This suggests that there is a mechanism outside the dopamine system that causes pain in PD. Our previous study demonstrated that 6-OHDA induced PD model manifested hyperalgesia to thermal and mechanical stimuli and decreased serotonin (5-hydroxytryptamine; 5-HT) in the spinal dorsal horn (SDH). Several 5-HT receptor subtypes have been confirmed to be associated with nociception in the spinal cord, such as 5-HT1A receptor, 5-HT1B receptor, 5-HT2 receptor, 5-HT3 receptor, and 5-HT7 receptor. Most research has shown that 5-HT1A receptor and 5-HT3 receptor play a key role in pain transmission in the spinal cord. We hypothesized that hyperalgesia of 6-OHDA rats may be related to increased excitability of SDH neurons, and functional change of 5-HT3 receptor may reverse the hyperalgesia of 6-OHDA lesioned rats and decrease cell excitability of SDH neurons. To test this hypothesis, we used whole-cell patch-clamp and pharmacological methods to evaluate the effect of 5-HT3 receptor and 5-HT1A receptor on the hyperalgesia of 6-OHDA rats. The results suggested that increased excitability in SDH neurons could be reversed by 5-HT3 receptor antagonist ondansetron (20 µmol/L) and palosetron (10 µmol/L), but not 5-HT3 receptor agonist m-CPBG (30 µmol/L) and SR 57,727 (10 µmol/L), 5-HT1A receptor agonist 8-OH DPAT (10 µmol/L) and eptapirone (10 µmol/L) and 5-HT1A receptor antagonist WAY-100635 (10 µmol/L) and p-MPPI (10 µmol/L). Intrathecal injection of ondansetron (0.1 mg/kg) but not m-CPBG (0.1 mg/kg), 8-OH DPAT (0.1 mg/kg), and WAY-100635 (0.1 mg/kg) significantly attenuated the mechanical hyperalgesia and thermal hyperalgesia in 6-OHDA lesioned rats. In conclusion, the present study suggests that inhibition of spinal 5-HT3 receptor and SDH neuronal excitability alleviates hyperalgesia in PD rats. Our study provides a novel mechanism or therapeutic strategy for pain in patients with PD.
Asunto(s)
Hiperalgesia , Enfermedad de Parkinson , Animales , Ratas , 8-Hidroxi-2-(di-n-propilamino)tetralin , Dopamina/farmacología , Hiperalgesia/complicaciones , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/inducido químicamente , Ondansetrón/farmacología , Ondansetrón/uso terapéutico , Oxidopamina/farmacología , Dolor , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Células del Asta Posterior , Receptor de Serotonina 5-HT1A , Receptores de Serotonina 5-HT3/fisiología , Serotonina/farmacología , Antagonistas del Receptor de Serotonina 5-HT3/farmacología , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Médula EspinalRESUMEN
BACKGROUND: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy. METHODS: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching. RESULTS: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine. CONCLUSIONS: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based chemotherapy.
Asunto(s)
Carboplatino , Náusea , Antagonistas del Receptor de Neuroquinina-1 , Antagonistas del Receptor de Serotonina 5-HT3 , Vómitos , Carboplatino/efectos adversos , Dexametasona/uso terapéutico , Humanos , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Olanzapina/uso terapéutico , Puntaje de Propensión , Estudios Prospectivos , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & controlRESUMEN
INTRODUCTION: Triple antiemetic therapy with neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone has been widely recommended for high emetogenic chemotherapeutic (HEC) agents and regimens, including anthracycline combined with cyclophosphamide (AC). The addition of olanzapine (OLZ) 5 mg or 10 mg to the recommended triple antiemetic therapy has demonstrated superiority in antiemetic efficacy compared with the standard triplet therapy for a cisplatin-based HEC regimen. Although OLZ plus the triple antiemetic treatment may also be effective for patients on an AC-based HEC regimen, no study has investigated its efficacy at a lower dose of 5 mg. METHODS AND ANALYSIS: To assess whether 5 mg OLZ, as compared with placebo, in combination with triple combination therapy, significantly improves nausea and vomiting, we are conducting a randomised, parallel-group controlled clinical trial with a total of 500 patients at 15 study centres in Japan. The primary outcome is the complete response rate, defined as no emetic episodes and no use of rescue medication during 120 hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of Juntendo University Hospital and relevant approval was obtained from all participating centres. All participants will be required to provide written informed consent. The trial results will be reported at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020.