Showing papers on "Granisetron published in 2007"

Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome

Abstract: The effect of granisetron, a specific 5-hydroxytryptamine 3-receptor antagonist, on the anorectal responses to rectal distension and a 1000-calorie meal was assessed in 12 patients with irritable bowel syndrome. Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline. Granisetron caused a dose-dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensations of gas, desire to defecate, urgency and discomfort were perceived. This reached significance for all sensations at the higher dose level (P < 0.01). No significant changes in anal pressures, rectal compliance or distension-induced motor activity occurred following drug administration. A dose-dependent reduction in post-prandial motility was observed following intravenous granisetron and this was highly significant at 160 mcg/kg (P = 0.005). These results suggest that the 5 hydroxytryptamine receptor antagonists may have a therapeutic role in patients with irritable bowel syndrome.

Review article: 5-hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications.

Abstract: SUMMARY Serotonin (5-hydroxytryptamine; 5-HT) is found in the enteric nervous system where it has been implicated in controlling gastrointestinal motor function. A number of receptor or recognition sites have been identified in the gut, but recently most attention has focused on the 5-HT3 and 5-HT4 receptors. The functional role of the 5-HT3 receptor remains incompletely understood, but it is probably involved in the modulation of colonic motility and visceral pain in the gut. A number of selective 5-HT3 antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride. While the substituted benzamide prokinetics (for example, metoclopramide, cisapride) also block 5-HT3 receptors in high concentrations, their prokinetic action is believed to be on the basis of their agonist effects on the putative 5-HT4 receptor. Some 5-HT3 antagonists have 5-HT4 agonist activity (for example, renzapride, zacopride) and others do not (for example, ondansetron, granisetron), while tropisetron in high concentrations is a 5-HT3 antagonist. Based on the pharmacological data, it has been suggested that specific 5-HT antagonists and agonists may prove to be beneficial in a number of gastrointestinal disorders including the irritable bowel syndrome, functional dyspepsia, non-cardiac chest pain, gastrooesophageal reflux and refractory nausea. In this review, the rationale for the use of these compounds is discussed, and the available experimental evidence is summarized.

Management of Postoperative Nausea and Vomiting in Children

Abstract: Postoperative nausea and vomiting (PONV) continues to be a frequent and important cause of morbidity in children. Postoperative vomiting (POV) is more commonly studied in children than postoperative nausea because of a child’s inability to effectively express distress after experiencing nausea. POV is problematic in children and is one of the leading postoperative complaints from parents and the leading cause of readmission to the hospital. POV occurs twice as frequently in children as in adults, increasing until puberty and then decreasing to adult incidence rates. Gender differences are not seen before puberty. POV remains a main cause of morbidity in children because severe vomiting can be associated with dehydration, postoperative bleeding, pulmonary aspiration, and wound dehiscence. While children have an increased potential for dehydration and the resulting physiologic impairments, other associated results such as a delay in hospital discharge or an overnight or longer hospital admission also must be considered. The two most common emetogenic surgical procedures evaluated in children are strabismus repair and adenotonsillectomy. The approach to the management of PONV and POV in children is similar to that in adults. However, as the rate of POV is more frequent in children than in adults, more children are candidates for antiemetic prophylaxis. The management approach is multifactorial and involves proper preoperative preparation, risk stratification, rational selection of antiemetic prophylaxis, choice of anesthesia technique, and a plan for postoperative antiemetic therapy. It is important to identify children at moderate-to-high risk for POV as prophylactic antiemetic therapy is useful in these children. Antiemetics of choice for POV in children include dexamethasone, dimenhydrinate, perphenazine, ondansetron, dolasetron, granisetron, and tropisetron. The serotonin (5-hydroxytryptamine; 5-HT3) antagonists are the antiemetic drugs of first choice for POV prophylaxis in children because as a group they have greater efficacy for preventing vomiting than nausea. The 5-HT3 antagonists can be effectively combined with dexamethasone with an increase in efficacy. If possible, regional anesthesia should be considered. For those undergoing general anesthesia, the baseline POV risk should be reduced. Children at moderate-to-high PONV risk should receive combination therapy with two or three prophylactic antiemetics from different antiemetic drug classes. Reference to and the use of PONV guidelines and management algorithms help improve cost-effective postoperative care.

Control of shivering during regional anaesthesia: prophylactic ketamine and granisetron

Abstract: Background: The aim of the present study was to compare placebo, ketamine, granisetron and a combination of ketamine and granisetron in the prevention of shivering caused by regional anaesthesia. Methods: In this prospective, randomized, double-blind study, 160 ASA I and II patients undergoing urological surgery were included. Subarachnoid anaesthesia was performed in all patients with bupivacaine 15 mg. The patients were randomly allocated to receive saline (group P, n= 40), ketamine 0.5 mg (group K, n= 40), granisetron 3 mg (group G, n= 40) or ketamine 0.25 mg + granisetron 1.5 mg (group KG, n= 40). Shivering was graded as 0 = no shivering, 1 = piloerection or peripheral vasoconstriction but no visible shivering, 2 = muscular activity in only one muscle group, 3 = muscular activity in more than one muscle group but not generalized, and 4 = shivering involving the whole body. If 15 min after spinal anaesthesia and concomitant administration of a prophylactic dose of one of the study drugs, the patients shivered according to at least grade 3, the prophylaxis was regarded as ineffective and intravenous (i.v.) pethidine 25 mg was administered. Results: After 15 min, the number of patients with observed shivering was 22 in group P, 6 in group G, 7 in group GK and 0 in group K. The difference between group K and all the other groups was statistically significant (P < 0.0001). The number of patients with a shivering score of 3 was statistically significantly higher in group P compared with the other groups. Conclusion: The prophylactic use of 0.5 mg/kg i.v. ketamine was effective in preventing shivering developed during regional anaesthesia.

A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis.

Abstract: Goals of work Comparing antiemetic efficacy of different 5-HT3-receptor antagonists (5-HT3RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV).

Prevention of postoperative nausea and vomiting in patients undergoing laparoscopic bariatric surgery--granisetron alone vs granisetron combined with dexamethasone/droperidol.

Abstract: BACKGROUND AND OBJECTIVES Laparoscopic bariatric surgeries are associated with an appreciably high rate of postoperative nausea and vomiting. This study was designed to compare the effectiveness of granisetron either alone or in combination with droperidol or dexamethasone, for the prevention of post operative nausea and vomiting (PONV) in patients undergoing laparoscopic bariatric surgeries. METHODS In a randomized, double-blind, placebo-controlled trial, 120 patients received either Granisetron 1 mg, Granisetron 1 mg plus Droperidol 1.25 mg, Granisetron 1 mg plus Dexamethasone 8 mg or Placebo (saline), intravenously immediately before induction of anesthesia. Perioperative anesthetic care was standardized in all patients. Patients were then observed for 24 hours after administration of the study drugs. RESULTS The incidence of PONV was 30% with granisetron alone, 30% with granisetron plus droperidol, 20%, with granisetron plus dexamethanone, and 67% with placebo. (P < 0.05; overall Fisher's exact probability test). The incidence of adverse events was not different among the 4 groups. CONCLUSION Graniserton is effective and safe drug for reducing the incidence of PONV in patients undergoing bariatric surgeries, and becomes highly effective when combined with dexamethasone.

Does ondansetron or granisetron prevent subarachnoid morphine-induced pruritus after cesarean delivery?

Abstract: BACKGROUND:We compared the efficacy of granisetron and ondansetron for the prevention of subarachnoid morphine-induced pruritus after cesarean delivery.METHODS:The incidence of pruritus was assessed in parturients who were randomly allocated into Group G (granisetron 3 mg IV, n = 45), Group O (ondan

Acute gastroenteritis in children: role of anti-emetic medication for gastroenteritis-related vomiting.

Abstract: Acute gastroenteritis is associated with significant morbidity in developed countries and each year is the cause of death of several million children in developing countries. Acute gastroenteritis is usually self-limiting. Oral rehydration therapy (ORT) is effective and successful in the majority of patients. Vomiting is common at the outset of viral gastroenteritis and can limit the effectiveness of ORT. Treatment with newer anti-emetic medications has been reported to facilitate ORT and to minimize the risk of dehydration and the need for intravenous hydration and hospitalization. The role of anti-emetic medications in the treatment of gastroenteritis-related vomiting is not clear. Some physicians agree with the use of anti-emetic medications because vomiting is unpleasant and distressing for the child and parents alike, and because vomiting can increase the likelihood of dehydration, electrolyte imbalance, and the need for intravenous hydration or hospitalization. Several surveys have shown that anti-emetic medications are commonly prescribed in the treatment of pediatric gastroenteritis and that adverse events are uncommon. Efficacy studies of the newer anti-emetic medications are now available and reveal that some are effective and help facilitate ORT. Other physicians disagree with the use of anti-emetic medications because acute gastroenteritis is a self-limiting condition, vomiting might help rid the body of toxic substances, there was previously a relative lack of published evidence of clinical benefit, and there are potential adverse events associated with the use of an anti-emetic medication. Anti-emetic medications that are currently available include ondansetron, granisetron, tropisetron, dolasetron, ramosetron, promethazine, dimenhydrinate, metoclopramide, domperidone, droperidol, prochlorperazine, and trimethobenzamide. Randomized, placebo-controlled trials suggest that ondansetron is efficacious and superior to other anti-emetic medications in the treatment of gastroenteritis-related vomiting. A recent double-blind clinical trial showed that a single oral dose of ondansetron reduces gastroenteritis-related vomiting and facilitates ORT without significant adverse events. Ondansetron shows promise as a first-line anti-emetic, and judicious use of this agent might increase the success of ORT, minimize the need for intravenous therapy and hospitalization, and reduce healthcare costs. Ondansetron should be considered in situations where vomiting hinders ORT, but a larger randomized, placebo-controlled trial is necessary before the medication can be routinely recommended for the treatment of gastroenteritis-related vomiting in children.

Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

Abstract: Objective. The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT3) antagonists in revolutionizing the management of platinum-based chemotherapy–induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT3 antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting clearly endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest.Methods. Data for patients (n¼159) receiving platinum-based chemotherapy regimens were retrospectively collected. Patients getting 5-HT3 antagonists without steroids or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics includ...

Intramuscular injection of granisetron into the masseter muscle increases the pressure pain threshold in healthy participants and patients with localized myalgia

Abstract: Objectives: The aims of this study were to experimentally investigate whether an intramuscular injection of the 5-HT 3 antagonist granisetron into the masseter muscle increases the mechanical pain threshold in healthy participants and reduces masseter muscle pain or allodynia in patients with craniofacial myalgia. Methods: Eighteen patients with bilateral localized myalgia of the masseter muscle and 24 healthy participants participated in this randomized, double-blind study, in which granisetron was injected on one side and isotonic saline on the other side. Pain (Visual Analog Scale) and pressure pain threshold (PPT) were recorded before and during 30 minutes after injections and the changes from baseline were analyzed with analysis of variance. Results: In both groups, the PPT increased after injection of granisetron whereas it decreased after saline. The difference between substances was significant (patients: P = 0.016; healthy participants: P = 0.029). In the healthy participants there was also a significant time effect (P < 0.001) and an interaction between time and substance (P = 0.022). The post-hoc test showed that the difference between substances was significant 0 to 15 minutes after injections (Bonferroni t test; P < 0.05). The pain intensity from the masseter muscle did not differ between substances, but there was a significant time effect (P < 0.001) and an interaction between time and substance (P < 0.001). The post-hoc test showed significantly lower pain intensity on the granisetron side 0 to 2 minutes after injections (Bonferroni t test; P < 0.05). Conclusions: This study indicates that intramuscular injection of granisetron into the masseter muscle increases the PPT in healthy participants and in patients with craniofacial myalgia.

The prophylactic granisetron does not prevent postdelivery nausea and vomiting during elective cesarean delivery under spinal anesthesia

Abstract: Background Intraoperative nausea and vomiting (IONV) during cesarean delivery (CD) under regional anesthesia has multiple etiologies, and the role of prophylactic antiemetics for prevention of IONV remains controversial. In this trial we sought to determine the efficacy of granisetron for prevention of IONV during elective CD under spinal anesthesia with strict control of the causative factors. Methods The study was conducted as a randomized, double-blind, placebo-controlled trial in 176 parturients. After administration of 10 mL/kg of lactated Ringer's solution, spinal anesthesia was administered with 0.75% hyperbaric bupivacaine 15 mg, fentanyl 10 microg, and morphine 100 microg. Systolic blood pressure was maintained at 100% of baseline with aliquots of phenylephrine. Oxytocin 0.5 IU was administered IV upon delivery followed by a maintenance infusion. The patients received either granisetron 1 mg or normal saline IV immediately after cord clamping. In case of persistent IONV, rescue dimenhydrinate 50 mg IV was administered. The primary outcome was the presence of postdelivery IONV. Secondary outcomes included the need for rescue antiemetic, hypotension, pain, and adverse effects. Results The incidence of postdelivery IONV was 20.4% in the granisetron group and 17.0% in the control group (P = 0.56, NS). The incidence of intraoperative hypotension, pre- (9.6%) and postdelivery (6.2%), was similar in both groups. The incidence of postdelivery pain (2.2% vs 4.5%, P = 0.68) and the requirement for rescue antiemetic (8% vs 6.8%, P = 0.77) were similar in the granisetron and control groups. Conclusions Despite strict control of the causative factors, IONV still affects 18% of patients undergoing elective CD, and prophylactic granisetron 1 mg is ineffective under the studied circumstances.

Effect of oral granisetron in uremic pruritus

Abstract: Background : Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Granisetron, is a potent and selective inhibitor of 5-HT3 receptors. There have been some studies about the effect of ondansetron in uremic pruritus and one case report has recently described relief of renal itch with granisetron. Aims : To evaluate the effect of Granisetron on uremic pruritus in Continuous Ambulatory Peritoneal Dialysis (CAPD) and Hemodialysis (HD) patients. Methods: To study the prevalence of uremic pruritus, patients on CAPD and HD were asked to complete a pruritus questionnaire.Their replies were scored based on numerical scales. Pruritus was graded, according to the total points for each patient, as mild, moderate or severe. Fourteen patients with moderate to severe pruritus were enrolled in the trial. During treatment, patients received granisetron (1 mg tablet twice a day P.O), for a period of 1 month. They were asked to score the severity of pruritus twice a day. Results : Seventy seven percent of the patients responded to the treatment and at 1 st , 2 nd and 4 th week the mean values of the pruritus scores were 23, 16 and 8 points respectively. Before starting treatment the score was 31 points ( P =0.03). Weekly clinical and laboratory examination showed no important side effects. Conclusion : Granisetron might be an effective, safe and well tolerated drug for the treatment of uremic pruritus.

Granisetron versus ondansetron treatment for breakthrough postoperative nausea and vomiting after prophylactic ondansetron failure: a pilot study.

Abstract: INTRODUCTION:Patients with an increased risk of postoperative nausea and vomiting (PONV) are frequently given prophylactic doses of a selective 5-hydroxytryptamine-3 antagonist (5HT3). In chemotherapy patients, it has been demonstrated that after unsuccessful treatment with one 5HT3 administering a

The effectiveness of inhalation isopropyl alcohol vs. granisetron for the prevention of postoperative nausea and vomiting.

Abstract: We evaluated preemptive treatment for postoperative nausea and vomiting (PONV) with intravenous (IV) granisetron, 0.1 mg, introoperatively as compared with the use of 70% inhalation isopropyl alcohol and a control group for the prevention of PONV. We randomly assigned 57 women, 18 to 50 years old, undergoing laparoscopic procedures to 1 of 3 groups: (1) inhalation of 70% isopropyl alcohol, (2) 0.1 mg granisetron IV, and (3) no prophylactic treatment control. Participants were asked to rate their nausea and vomiting preoperatively, on arrival to postanesthesia care unit (PACU), at discharge from PACU, 6 hours after extubation, and 24 hours after extubation and any occurrence of nausea and vomiting using the numeric rating scale (NRS), 0 to 10. Group 1 experienced more PONV episodes than groups 2 and 3 during the 6- to 24-hour postsurgical timeframe (P = .02). There were no significant differences among the 3 groups in demographics, first episode of PONV, total number of episodes in 24 hours, NRS rating at rescue, and anesthetic duration. PONV and menstrual cycle phase had no positive correlation (P > .05). History of smoking, PONV, and motion sickness had no significant difference against any measure of PONV (P > .05).

Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: A comparison of efficacy, side-effect profile, and cost

Abstract: Background: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. Methods: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. Results: The complete response (CR) rates in the control of acute emesis were 80.4 per...

Comparison of the effectiveness of metoclopramide, ondansetron, and granisetron on the prevention of nausea and vomiting after laparoscopic cholecystectomy.

Abstract: Background and Goals: A relatively high incidence of postoperative nausea and vomiting (PONV) occurs in patients undergoing a laparoscopic cholecystectomy. Prophylaxis of PONV is usually achieved with a single-dose antiemetic drug administered during the surgical procedure. The aim of the current study was to compare the antiemetic activity of different 5-hydroxytryptamine-3 receptor antagonists with that of metoclopramide. Materials and Methods: In a randomised, double-blind study, 75 patients received the following: Group M, 10 mg metoclopramide; Group K, 40 mcg · kg−1 granisetron; and Group Z, 15 mcg · kg−1 ondansetron intravenously (IV) diluted in 20 cc 0.9% NaCl (n = 25 of each) i.v. immediately before the induction of anesthesia. The standard general anesthetic technique, which consisted of sevoflurane in air-oxygen and a fentanyl perfusion, was used. Nausea, vomiting, and safety assessments were performed continuously during the first 24 hours after anesthesia. Results: There were no statistically ...

Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy.

Abstract: Background. 5-HT3-receptor antagonists are one of the mainstays of antiemetic treatment, and they are administered either i.v. or orally. Nevertheless, sometimes neither administration route is feasible, such as in patients unable to admit oral intake managed in an outpatient setting.Ourobjectivewastoevaluatethebioavailability of s.c. granisetron. Patients and Methods. Patients receiving platinumbased chemotherapy were randomized to receive 3 mg of granisetron either s.c. or i.v. in a crossover manner during two cycles. Blood and urine samples were collected after each cycle. Pharmacokinetic parameters observed with each administration route were compared by analysis of variance. Results. From May to November 2005, 31 patients were included and 25 were evaluable. Subcutaneous granisetron resulted in a 27% higher area under the concentration‐time curve for 0‐12 hours (AUC0‐12h) and higher levels at 12 hours, with similar values for AUC0‐24h. The maximum concentration was lower with the s.c. than with the i.v. route and was observed 30 minutes following s.c. administration. Conclusion. Granisetron administered s.c. achieves complete bioavailability. This is the first study that shows that s.c. granisetron might be a valid alternative to i.v. delivery. Further trials to confirm clinical equivalence are warranted. This new route of administration mightbeespeciallyrelevantforoutpatientmanagement of emesis in cancer patients. The Oncologist 2007;12: 1151–1155

Is ondansetron more effective than granisetron for chemotherapy-induced nausea and vomiting? A review of comparative trials.

Abstract: Nausea and vomiting are two of the most distressing side effects of chemotherapy. Guidelines recommend the use of 5-HT3 receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting for moderately and highly emetogenic chemotherapy. Although newer antiemetics and 5-HT3 receptor antagonists are available, ondansetron and granisetron still are used widely. A review of the literature was conducted to identify trials that compared the antiemetic efficacy of ondansetron and granisetron. Studies were identified by searching the PubMed, EMBASE, Ovid MEDLINE, CINAHL, and Evidence-Based Medicine Reviews databases. The six studies reviewed in this article were either a meta-analysis; a randomized, controlled trial; or another type of research study published from 2000 to date. The results reported in the studies reveal that ondansetron and granisetron have equal antiemetic efficacy in reducing or eliminating chemotherapy-induced nausea and vomiting (CINV), with the evidence classified as good based on U.S. Preventive Services Task Force criteria for judging the strength of the overall evidence. Although side effects of ondansetron and granisetron have been reported, they normally are mild and of brief duration, not severe or lasting enough to warrant discontinuation.

Effects of ondansetron and granisetron on postoperative nausea and vomiting in adult patients undergoing laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled clinical trial.

Abstract: Background: Postoperative nausea and vomiting (PONV) are common and potentially distressing adverse events (AEs) associated with surgery and anesthesia. In patients undergoing laparoscopic cholecystectomy (LC) without antiemetic prophylaxis, the incidence of PONV can be as high as 72%. Objective: The aim of this study was to investigate the prophylactic antiemetic effects of ondansetron and granisetron in patients undergoing LC when these agents are administered before the end of surgery. Methods: Patients classified by the American Society of Anesthesiologist's physical status as I or II who were scheduled for elective LC were included in this randomized, double-blind, placebo-controlled study. Anesthesia was induced with thiopental 5 mg/kg and fentanyl 2 μg/kg, and was maintained with isoflurane 1% to 3% in 50% oxygen and 50% nitrous oxide and fentanyl as needed. Approximately 20 to 30 minutes before the end of the surgery, the patients randomly received either IV ondansetron 100 μg/kg (group O), IV granisetron 40 μg/kg (group G), or normal saline (group P). Plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined preoperatively and 24 hours postoperatively. The patients were observed for 24 hours for PONV and other possible AEs. Postoperative pain intensity was determined using a 10-cm visual analogue scale. Four-point satisfaction scores were determined at 24 hours. Results: Ninety patients (69 women, 21 men) participated in the study. Demographic characteristics and operative data (duration of surgery and anesthesia and amount of intraoperative fentanyl) were similar in the 3 groups. The only AE reported by patients during the 24-hour observation period was nonsevere headache. The number of patients experiencing headache was similar in group P, group O, and group G (10 [33%] patients, 6 [20%], and 10 [33%], respectively). No significant changes were found in presurgical and postsurgical plasma levels of ALT and AST in any group. The mean (SD) satisfaction scores in group O and group G (3.0 [0.4] and 3.0 [0.6], respectively) were significantly higher than those in group P (2.5 [0.5]; both, P < 0.01). Immediately after surgery (period 0), significantly more patients in the placebo group (21 [70%]) experienced PONV compared with those in the ondansetron group (9 [30%]; P < 0.05) and the granisetron group (7 [23%]; P < 0.01). During the 24-hour observation period, a significantly greater number of patients in group P (18 [60%]) required a single dose of a rescue antiemetic drug compared with those in groups O and G (9 [30%] and 6 [20%], respectively; both, P < 0.01). Conclusions: Patients administered ondansetron 100 μg/kg or granisetron 40 μg/kg 20 to 30 minutes before the end of LC had significantly higher PONV control during the 24-hour postoperative observation period than patients receiving placebo. However, there were no significant differences between the active treatment groups in the incidence of PONV, patient satisfaction, or AEs.

Superior anti‐emetic efficacy of granisetron–dexamethasone combination in children undergoing middle ear surgery

Abstract: Aim: To compare the effectiveness of granisetron and a granisetron–dexamethasone combination for the prevention of post-operative vomiting in children undergoing middle ear surgery. Methods: Ninety ASA physical status I or II children, aged 3–12 years, were randomly assigned to three groups of 30 each to receive a single dose of placebo (normal saline), granisetron 40 μg/kg or a combination of granisetron 40 μg/kg and dexamethasone 150 μg/kg intravenously after the induction of anaesthesia. Peri-operative anaesthetic care was standardized in all children. Post-operatively, during the first 24 h after anaesthesia, the frequencies of retching and vomiting and the incidence of adverse events were recorded. Rescue anti-emetic was administered if two or more episodes of emesis occurred. Post-operative pain was treated with morphine intravenously, followed by acetaminophen orally. Results: There were no differences between the treatment groups with regard to demographic data. A complete response (no retching/vomiting and no need for rescue anti-emetic) was achieved in 50%, 80% and 96.67% of children who received saline, granisetron and granisetron–dexamethasone, respectively (P < 0.05). Six children who received placebo and one who received granisetron alone required another rescue anti-emetic. The incidence of adverse events was comparable in the three groups. Conclusion: The prophylactic granisetron–dexamethasone combination was more effective than granisetron alone in the prevention of post-operative emesis during the first 24 h after anaesthesia in children undergoing middle ear surgery.

A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy

Abstract: Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin. In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 μg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1–23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 μg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls. Patients in the granisetron 10 and 40 μg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated. We conclude that granisetron 10 and 40 μg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.

Intractable nausea and vomiting successfully related with granisetron 5-hydroxytryptamine type 3 receptor antagonists in Palliative Medicine.

Abstract: Sir—The selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, such as ondansetron and granisetron, are well accepted in the treatment of nausea and vomiting related to chemotherapy, surgery and pregnancy.1 Their use within palliative care patients is documented but uncommon.2,3 5-HT3 antagonists competitively bind receptors within gut vagal afferents and areas of the central nervous system (CNS) related to nausea, such as the chemoreceptor trigger zone and the nucleus tractus solitarii.1 This dual activity within the gut and higher vomiting centres would suggest possible utility within the palliative care population. There is observed individual variability in response to each of these drugs.1 5HT-3 antagonists differ in chemical structure, dose–response, metabolic pathways and receptor interaction.1,4,5 Individual 5-HT3 antagonists are metabolised by different components of the cytochrome P450 system. These case histories describe two patients with intractable nausea and vomiting who responded to granisetron when other anti-emetics, including ondansetron, failed to gain control.

Nasal absorption studies of granisetron in rats using a validated high-performance liquid chromatographic method with mass spectrometric detection.

Abstract: Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although forms of the drug are commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liq uid chromatography method with mass spectrometric detection (LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. Granisetron was separated in a reverse-phase C-18 column without interference from other components of plasma. This method involves a rapid assay for the determination of granisetron in a small volume of plasma with a run time of 12 min using ondansetron as an internal standard. Data were acquired in the electrospray ionization (ESI) mode with positive ion detection and application of single ion recording (SIR). Granisetron and ondansetron were detected at m/z values of 313.2 and 294.2, respectively. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. To date, the first pharmacokinetic study after intranasal administration of granisetron was performed and some pharmacokinetic parameters were presented in this paper. Granisetron was found to be well absorbed through nasal route and the bioavailability of this drug following nasal administration was comparable with that of intravenous administration.

Skipping day 2 antiemetic medications may improve chemotherapy induced delayed nausea and vomiting control: results of two pilot phase II trials.

Abstract: Background 5HT-3 antagonists and corticosteroids control less than 50% of delayed chemotherapy induced nausea and vomiting (CINV) episodes.

A Comparative Study Of Premedication For Prevention Of Vomiting Induced By Intrathecal Calcitonin: A Double Blind Study

Abstract: Background: The aim of this study was to study the complications and to compare the effects of the antiemetic premedication on incidence of nausea and vomiting induced by sub-arachnoid bupivacaine and calcitonin. Material and Method: In a prospective, double-blind, randomized sequential allocated study, 80 ASA I and II physical status patients received 0.5% bupivacaine with 100 i.u salmon calcitonin in sub-arachnoid space and were divided into four groups of 20 each. Group I received chlorpromazine, Group II received dexamethsone, Group III received Granisetron, and Group D received no antiemetic as premedication. Results and Conclusion: The incidence of postoperative nausea vomiting is highly variable following subarachnoid blockade with a further increase in incidence observed upon addition of additives to increase the duration of analgesia. Granisetron is a potent antiemetic among dexamethsone and chlorpromazine for prevention of postoperative nausea vomiting.

The 5-HT3 receptor antagonist granisetron lowers clonic seiure threshold in pentylenetetraole induced seiure in mice: The involvement of nitric oxide system

Abstract: Background and Objective: There are at least 7 classes of receptors known for serotonin (also well known as 5-hydroxy tryptamine: 5-HT); among them 5-HT3 is completely distinct. It is a ligand-dependent cation channel highly permeable to calcium. 5-HT3 receptors are found postsynaptically in GABAergic cortical and limbic neurons beside a variety of other regions. 1 According to accumulating evidences, epileptic seizures can be induced and/or augmented by attenuation of serotonergic neurotransmission. In contrast, manipulations increasing serotonin function (like fluoxetin administration) generally suppress epileptic seizures in animals. 2 Nitric oxide (NO) is a small membrane-diffusing molecule synthesized by nitric oxide synthase (NOS). NO is found to be a modulator of seizure susceptibility with either anticonvulsant or proconvulsant effects in different seizure paradigms. We evaluated the effect of the 5-HT3 antagonist granisetron on clonic seizure induced by pentylenetetrazole (PTZ) and the potential connection with the NO system. Methods: PTZ (1%) was infused at a constant rate through tail vein catheter of male Swiss mice and halted when clonus followed by falling was observed. Minimal dose of PTZ (mg/kg of mice weight) needed to induce clonic seizure was measured as an index of seizure threshold. The interaction of granisetron effects with NO was examined using NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) and NOS substrate L-arginine. Results and Discussion: L-NAME could increase seizure threshold in its effective dose (100mg/kg, p<0.01). On the other hand, L-arginine showed a proconvulsive effect in doses higher than 100 mg/kg (p<0.01). Mice pretreated with granisetron had lower threshold than controls (31.37 versus 36.95 mg/kg, p<0.01) which could be reversed by effective doses of L-NAME (up to baseline). Co-administration of subeffective doses of granisetron and L-arginine (3 and 75 mg/kg, respectively) demonstrated a synergistic effect (p<0.05). Our results confirm the proconvulsant role of NO. The 5-HT3 receptor antagonist granisetron also showed a proconvulsant effect in this model, probably as a consequence of decreased excitation of GABAergic inhibitory neurons. The interaction of L-NAME and L-arginine with granisetron suggest that 5-HT3 and NO may be in line in a neuronal signaling pathway, presumably through calcium mediated signaling pathways increased by 5-HT3 activation. Conclusion: The NO system involvement is described in the 5-HT3 channel/receptor for the first time. An anticonvulsive role could be presumed for 5-HT3 agonists, which could lead to further research on a new class of antiepileptic drugs.