Understanding Australian Pharmacists' Perceptions on the Utilisation of Oral 5-HT3 Antagonists as Pharmacist-Only Anti-Emetics in Comparison to Oral D2 Antagonists.

Objectives: To investigate the perception of community pharmacists on the down-scheduling of 5-HT3 antagonists to pharmacist-only-medicine for treatment of acute nausea and/or vomiting in Australia. Methods: A nationwide anonymous survey targeting Australian community pharmacists was conducted from April to May 2023. Responses were collected and analysed quantitively or qualitatively, where appropriate. Key findings: Participants reported that 5-HT3 antagonists were effective at treating nausea and/or vomiting and would likely recommend their use. Training is required to manage supply due to concerns related to their side effects. Conclusion: Participants supported down-scheduling of 5-HT3 antagonists for the treatment of nausea and/or vomiting in Australia. A pilot study on the provision of 5-HT3 antagonists by pharmacists is recommended as is the development of guidelines for pharmacist-only supply before down-scheduling is considered.

The intraperitoneal ondansetron for postoperative pain management following laparoscopic cholecystectomy: A proof-of-concept, double-blind, placebo-controlled trial.

BACKGROUND: Pain after laparoscopic cholecystectomy remains a major challenge. Ondansetron blocks sodium channels and may have local anesthetic properties. AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy. METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups. RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively). CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.

Evidence-based clinical practice guidelines for irritable bowel syndrome 2020.

Managing irritable bowel syndrome (IBS) has attracted international attention because single-agent therapy rarely relieves bothersome symptoms for all patients. The Japanese Society of Gastroenterology (JSGE) published the first edition of evidence-based clinical practice guidelines for IBS in 2015. Much more evidence has accumulated since then, and new pharmacological agents and non-pharmacological methods have been developed. Here, we report the second edition of the JSGE-IBS guidelines comprising 41 questions including 12 background questions on epidemiology, pathophysiology, and diagnostic criteria, 26 clinical questions on diagnosis and treatment, and 3 questions on future research. For each question, statements with or without recommendations and/or evidence level are given and updated diagnostic and therapeutic algorithms are provided based on new evidence. Algorithms for diagnosis are requisite for patients with chronic abdominal pain or associated symptoms and/or abnormal bowel movement. Colonoscopy is indicated for patients with one or more alarm symptoms/signs, risk factors, and/or abnormal routine examination results. The diagnosis is based on the Rome IV criteria. Step 1 therapy consists of diet therapy, behavioral modification, and gut-targeted pharmacotherapy for 4 weeks. For non-responders, management proceeds to step 2 therapy, which includes a combination of different mechanistic gut-targeted agents and/or psychopharmacological agents and basic psychotherapy for 4 weeks. Step 3 therapy is for non-responders to step 2 and comprises a combination of gut-targeted pharmacotherapy, psychopharmacological treatments, and/or specific psychotherapy. These updated JSGE-IBS guidelines present best practice strategies for IBS patients in Japan and we believe these core strategies can be useful for IBS diagnosis and treatment globally.

Antiemetic Prophylaxis with Fosaprepitant and 5-HT3-Receptor Antagonists in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

BACKGROUND: High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available. METHODS: A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8-32 mg/24h) or granisetron (2 x 40 µg/kg∙d-1) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0-24h, >24-120h, >120-240h). RESULTS: Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (p>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0-24h (64 vs 22 events; p<0.01), >24-120h (135 vs 78 events; p<0.0001), >120-240h (268 vs 105 events; p<0.0001), and the whole observation period 0-240h (467 vs 205 events; p<0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24-120h (100% vs 74.3%) but not the other analyzed time periods (p>0.05). CONCLUSION: The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.

Extended release granisetron: Review of pharmacologic considerations and clinical role in the perioperative setting.

In this review, we evaluate recent literature on use of ER granisetron in clinical practice as compared with current antiemetics and describe its potential uses for perioperative PONV prophylaxis and treatment. Recent literature was evaluated on ER granisetron use compared with currently used antiemetic agents ondansetron, droperidol, metoclopramide, promethazine, and dexamethasone with a focus on procedural anti-emesis. Though promising great effect, application of extended release granisetron to clinical use may be limited by it's increased relative cost.

Granisetron: a review of pharmacokinetics and clinical experience in chemotherapy induced - nausea and vomiting.

INTRODUCTION: Chemotherapy induced nausea and vomiting (CINV) are major side effects of chemotherapy and a great burden to patients' quality of life. Serotonin and substance P are the major neurotransmitters involved in the pathophysiology of CINV, but in spite of new antiemetics no completely effective regime exists for its prevention or treatment. Areas covered: In this review the authors provide a detailed description of granisetron's chemistry pharmacokinetics, pharmacodynamics, toxicity and a brief review of clinical trials involving granisetron and the management of CINV. We searched reviews, meta-analysis and randomized controlled trials (Medline, Embase and article reference lists). Expert opinion: According to current literature, granisetron 2 mg orally or 0,01mg/kg (1 mg) intravenously per day, co-administered with dexamethasone and NK-1 antagonists is the recommended regime for highly emetogenic chemotherapy. In the future the role of transdermal and subcutaneous formulations against delayed CINV will be clarified and probably enhance patients' convenience.

5-HT3 receptors antagonists reduce serotonin-induced scratching in mice.

Serotonin (5-hydroxytryptamine, 5-HT) acts as a pruritogen in humans and animals, but the mechanisms of action through that serotonin induces itch response have not been extensively discovered. In our study, we attempted to investigate the role of 5-HT3 receptors in scratching behavior due to intradermal serotonin injection. Intradermal injection of serotonin (14.1-235 nmol/site) into the nape of the neck of mice was performed to elicit itch. Scratching behavior was evaluated by measuring the number of bouts during 60 min after injection. We evaluated the effect of intraperitoneal pretreatment with ondansetron and tropisetron (0.1, 0.3, and 1 mg/kg) on itch induced by serotonin. Also, intradermal ondansetron and tropisetron at doses 50, 100, and 200 nmol/site were concurrently administrated with serotonin. Serotonin produced a significant enhancement in scratching at dose 141 nmol/site. Concurrent administration of ondansetron (50, 100, and 200 nmol/site) and tropisetron (100 and 200 nmol/site) with serotonin reduced scratching activity compared to the animals that only received serotonin. Also, pretreatment with intraperitoneal ondansetron and tropisetron (0.3 and 1 mg/kg) 30 min before serotonin attenuated the itch response. We showed that the scratching induced by intradermal serotonin is mediated by 5-HT3 receptors subtype. It can be concluded that 5-HT3 may play a role in mediating serotonin-associated itch responses, and we introduce 5-HT3 receptors as possible targets for antipruritic agents.

Phenothiazine vs 5HT3 antagonist prophylactic regimens to prevent Post-Anesthesia Care Unit rescue antiemetic: an observational study.

PURPOSE: Our practitioners are asked to consider a patient's postoperative nausea and vomiting (PONV) risk profile when developing their prophylactic antiemetic strategy. There is wide variation in employed strategies, and we have yet to determine the most effective PONV prophylactic regimen. The objective of this study is to compare prophylactic antiemetic regimens containing: phenothiazines to 5HT3 antagonists for effectiveness at reducing the incidence of Post-Anesthesia Care Unit (PACU) rescue antiemetic administration. METHODS: This is an observational study of 4,392 nonsmoking women who underwent general anesthesia for breast surgery from 1/1/2009 through 6/30/2012. Previous history of PONV or motion sickness (HxPONV/MS) and the use of PACU opioids were recorded. Prophylactic antiemetic therapy was left to the discretion of the anesthesia care team. We compared phenothiazines and 5HT3 antagonists alone and with a glucocorticoid to determine the most effective treatment regimen in our practice for the prevention of the administration of PACU rescue antiemetics. RESULTS: Patients who received a phenothiazine regimen compared to a 5HT3 antagonist regimen were less likely to have an antiemetic administered in the PACU (p=0.0100) and this significant difference in rates holds in a logistic regression model adjusted for HxPONV/MS and PACU Opioid use (p=0.0103). CONCLUSIONS: Based on our findings our clinicians are encouraged to administer a combination of a phenothiazine and a glucocorticoid in female, nonsmoking surgical breast patients for the prevention of PACU rescue antiemetic administration.

Granisetron versus ondansetron for post-operative nausea and vomiting prophylaxis in elective craniotomies for brain tumors: A randomized controlled double-blind study.

CONTEXT: Post-operative nausea and vomiting (PONV) pose unique challenges in neurosurgical patients that warrant its study separate from other surgical groups. SETTING AND DESIGN: This prospective, randomized, double-blind study was carried out to compare and to evaluate the efficacy and safety of three antiemetic combinations for PONV prophylaxis following craniotomy. MATERIALS AND METHODS: A total of 75 anesthesiologist status I/II patients undergoing elective craniotomy for brain tumors were randomized into three groups, G, O and D, to receive single doses of dexamethasone 8 mg at induction with either granisetron 1 mg, ondansetron 4 mg or normal saline 2 ml at the time of dural closure respectively. Episodes of nausea, retching, vomiting and number of rescue antiemetic (RAE) were noted for 48 h post-operatively. STATISTICAL ANALYSIS: Analysis of variance with post-hoc significance and Chi-square test with fisher exact correction were used for statistical analysis. P <0.05 was considered to be significant and P < 0.001 as highly significant. RESULTS: We found that the incidence and number of vomiting episodes and RAE required were significantly low in Group G and O compared with Group D; P < 0.05. However, incidence of nausea and retching were comparable among all groups. The anti-nausea and anti-retching efficacy of all the three groups was comparable. CONCLUSIONS: Single dose administration of granisetron 1 mg or ondansetron 4 mg at the time of dural closure with dexamethasone 8 mg provide an effective and superior prophylaxis against vomiting compared with dexamethasone alone without interfering with post-operative recovery and neurocognitive monitoring and hence important in post-operative neurosurgical care.

Antiemetic effects of dexamethasone and ondansetron combination during cesarean sections under spinal anaesthesia.

BACKGROUND: Nausea and vomiting are frequently seen in patients undergoing cesarean section (CS) under regional anesthesia. We aimed to compare the antiemetic efficacy of ondansetron and dexamethasone combination with that of the use of each agent alone to decrease the incidence of post-delivery intraoperative nausea and vomiting (IONV) during CS under spinal anesthesia. OBJECTIVE: To compare the antiemetic efficacy of ondansetron and dexamethasone combination with that of the single use of each agent to decrease the incidence of postdelivery IONV during CS under spinal anesthesia. METHODS: A randomized, prospective, double blind study was performed on 90 patients undergoing planned CS under spinal anesthesia. Patients received 4mg ondansetron in Group O, 8mg dexamethasone in GroupD, 4mg ondansetron+8mg dexamethasone in Group OD intravenously within 1-2 minutes after the umbilical cord was clamped. Frequency of postdelivery IONV episodes was recorded. RESULTS: A total of 86 eligible patients were included in the study. There were 29 patients in Group O, 29 patients in Group D and 28 patients in Group OD. There were no statistically significant difference between the groups in terms of baseline characteristics and intraoperative managements. Frequency of intraoperative nausea, retching and vomiting experiences were similar between the groups (p>0.05). CONCLUSION: Single dose 4mg ondansetron, 8mg dexamethasone, or combined use of 8mg dexamethasone+4mg ondansetron, given intravenously is all effective agents for the control of postdelivery IONV. Combined use of dexamethasone and ondansetron for the same indication does not seem to increase the antiemetic efficacy.

Pathophysiology of nausea and vomiting in palliative medicine.

Nausea/vomiting remains a significant problem in medicine, especially in patients with chronic illnesses. The incidence and patient distress level from nausea and vomiting are underestimated by health care providers. A thorough patient evaluation followed by rational polypharmacy and a multimodal treatment approach may minimize the occurrence and intensity of nausea/vomiting. Utilizing new techniques (e.g., PET imaging of the CNS with novel radiotracers, functional Magnetic Resonance Imaging), clinicians could have a greater chance to elucidate which receptors may be contributing to an individual's experience of nausea and vomiting and the relative importance of each. Future research into assessing precise mechanisms of nausea and vomiting in particular patients may enable clinicians to design the most appropriate combinations of antiemetics in efforts to achieve the most effective therapy with the least side effects. Individually-tailored antiemetic "cocktails," based on patient specific pathophysiology, may lead to optimal treatment outcomes.

Reappraisal of the role of dolasetron in prevention and treatment of nausea and vomiting associated with surgery or chemotherapy.

Chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting are one of the most frequent but also very concerning consequences for patients undergoing chemotherapy or surgical procedures under general anesthesia. There are a variety of mechanisms involved in the activation of nausea and vomiting. Serotonin, a ubiquitous central and peripheral neurotransmitter, is thought to be the predominant mediator of the perception of nausea and triggering of the vomiting response in both the brain and the periphery via the 5-hydroxytryptamine type 3 (5-HT(3)) receptor pathways. 5-HT(3) receptor antagonists disrupt this pathway, largely at the level of the vagal afferent pathways, to decrease nausea and vomiting. This review will focus on dolasetron, an older but sill commonly used 5-HT(3) receptor antagonist and its multimodal mechanism of action, safety and tolerability, patient considerations, and a review of the current literature on its use to combat both chemotherapy-induced and postoperative nausea and vomiting in these two important patient populations.

5-HT3 receptor antagonists for the treatment of nausea/vomiting.

It is well appreciated that a number of things (e.g., various insults, chemotherapeutic agents, radiation) may lead to the release of serotonin from the enterochromaffin of the gastrointestinal tract. Released serotonin may then bind to certain 5-HT3 receptors and promote nausea/vomiting. 5-HT3 receptor antagonists may ameliorate nausea/vomiting in a number of circumstances and have been utilized as important antiemetics for multiple conditions such as chemotherapy-induced nausea/vomiting (CINV), radiation-induced emesis (RIS), and postoperative nausea/vomiting (PONV).