Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Work on the pharmacological effects of high-dose metoclopramide led Beecham scientists to identify the role of 5-HT3 receptors in the emetic response to cytostatic drugs and X-irradiation in animals. Further studies have confirmed and extended knowledge of the novel 5-HT3 antagonist granisetron. Dose-dependent inhibition of the 5-HT-induced Bezold-Jarisch reflex in anaesthetized rats was shown by doses of 0.1-10 micrograms/kg i.v. granisetron. Radioligand binding studies in rat brain revealed a high affinity (Ki 0.26 nM) for 5-HT3 sites and much lower affinities (Ki 1000 - greater than 10,000 nM) for 5-HT1, 5-HT2, 5-HT1A, 5-HT1B/C, 5-HT1C, alpha 1, alpha 2, dopamine D2, benzodiazepine, picrotoxin, beta, histamine H1 or opioid mu, kappa or delta binding sites. Granisetron was effective prophylactically after oral or i.v. doses or by intervention after i.v. doses (0.005-0.5 mg/kg) against cisplatin, cyclophosphamide and doxorubicin or X-irradiation-induced emesis in the conscious ferret in the absence of any side effects. It was concluded therefore, that granisetron is a selective and potent anti-emetic worthy of clinical investigation.
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PMID:The role of specific 5-HT3 receptor antagonism in the control of cytostatic drug-induced emesis. 216 86

Cancer therapy with cytotoxic drugs such as cisplatin or cyclophosphamide is usually associated with violent crisis of vomiting. Recently, it was shown that 5-HT3 receptor antagonists block cisplatin-induced vomiting but the mechanisms and their sites of action remain unknown. We tested the hypothesis that these agents act on structures within the central nervous system by evaluating the effectiveness of vagal stimulation in eliciting fictive vomiting in decerebrate, paralyzed and ventilated cats before and after administration of such agents. Fictive vomiting was defined as a series of large bursts of synchronous activity in the phrenic and abdominal (expiratory) nerves (retching) followed by a burst in which the abdominal activity was prolonged (expulsion). The latency and number of these co-activations were measured before and after intravenous administration of three 5-HT3 receptor antagonists (GR 38032F (Ondansetron). Zacopride, and BRL 43694A (Granisetron]. All compounds, administered at doses of 1 and 2 mg/kg failed to block vomiting behaviour in 100% and 68% of trials, respectively. Nor did their administration affect the latency and number of co-activations. We conclude that intravenous administration of 5-HT3 receptor antagonists do not act centrally on either the brainstem neuronal network known as the "vomiting center" or related neuronal structures. Our results suggest that the anti-emetic effect of 5-HT3 receptor antagonists in cisplatin-induced vomiting is mediated peripherally rather than centrally.
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PMID:Vagal-induced vomiting in decerebrate cat is not suppressed by specific 5-HT3 receptor antagonists. 229 1

As part of an open dose-ranging study, the pharmacokinetics of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist given by the i.v. route, was studied in 18 patients receiving highly emetogenic cytotoxic drugs, predominantly cisplatin, either alone or in combination with other cytostatic agents. All patients received 30-min infusions of granisetron at a dose of 40 micrograms/kg. Nine showed complete absence of the gastrointestinal side effects normally associated with cisplatin, and in the majority of the remaining patients, the onset and severity of nausea was significantly modified. No acute side effects were observed at this dose and the drug was well tolerated in all cases. Peak plasma concentrations and area under the curve (AUC) values for granisetron showed considerable inter-patient variation. Higher plasma levels of granisetron were observed at 5 h in responding patients compared with those in whom the drug was ineffective in controlling emesis (P less than 0.05). AUC values were higher in responding patients, but this difference was not statistically significant. There was apparently no defined plasma concentration threshold for the drug's anti-emetic effect in these patients. Granisetron seems to be an effective and safe anti-emetic in patients receiving cytotoxic chemotherapy. Further exploration of its dose scheduling and pharmacokinetic profile is warranted.
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PMID:A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response. 254 37

Granisetron is a selective serotonin3 (5-hydroxytryptamine3, 5-HT3) receptor antagonist which has significant antiemetic activity against chemotherapy-induced nausea and vomiting. A single prophylactic intravenous dose is sufficient to control acute nausea and vomiting in approximately 60 to 70% of patients. In comparative studies, the acute antiemetic efficacy of granisetron is equivalent or superior to that of traditional antiemetic regimens even in patients receiving highly emetogenic cisplatin-containing chemotherapy. However, limited data have suggested that granisetron therapy offers no advantages over traditional antiemetics in terms of the control of delayed emesis. Recently, a number of large randomised studies have directly compared the efficacy and tolerability of granisetron, ondansetron and tropisetron and reported no significant differences between the 3 drugs in controlling acute nausea and vomiting, although 1 study reported a modest statistical advantage for granisetron over ondansetron but not tropisetron in the complete control of vomiting. In crossover studies, significantly more patients preferred granisetron to either ondansetron or tropisetron. The efficacy of granisetron appears to be maintained with repeated doses over several cycles of chemotherapy, although the influence of various prognostic factors affecting antiemetic response has not been adequately analysed. Concomitant administration of dexamethasone significantly improves the acute antiemetic efficacy of granisetron, increasing response rates by approximately 15%. Granisetron is an effective antiemetic in children undergoing highly emetogenic chemotherapy, and effectively controls radiotherapy-induced and postoperative nausea and vomiting. Trials using an oral formulation are scarce at present, but preliminary results suggest a similar efficacy and tolerability profile to that of the intravenous formulation. Granisetron has been well tolerated in clinical trials. The most frequently reported adverse event has been headache (14%). Extrapyramidal effects, which can limit the use of traditional antiemetics such as metoclopramide, have not been reported with granisetron. Thus, recent data confirm that granisetron is an effective and well tolerated agent for the prophylactic treatment of chemotherapy-induced acute nausea and vomiting, with efficacy equivalent or superior to that of other currently available agents. It has a promising role to play in paediatric oncology, and is an effective agent in controlling radiotherapy-induced acute emesis. Granisetron offers comparable or superior efficacy in controlling acute nausea and vomiting with a much simpler dosage regimen than that of traditional antiemetic regimens.
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PMID:Granisetron. An update of its therapeutic use in nausea and vomiting induced by antineoplastic therapy. 753 Jun 31

Forty patients with bladder cancer who underwent radiotherapy with angiotensin II, a hypertensor, and two cycles of arterial infusion of anticancer chemotherapies, including cisplatin 100 mg/body, were randomly assigned to a granisetron group and a non-granisetron group for comparative study of its prophylactic effect on nausea, vomiting and anorexia. Granisetron proved significantly effective in preventing nausea, as 75% of granisetron-administered patients experienced either only slight nausea or none at all, against only 22.5% in the non-granisetron group. The number of vomiting episodes was zero during the three-day observation period in 28 out of 40 (70%) granisetron-administered patients compared with 6 patients (15%) in the non-granisetron group. A significant difference in prophylactic effect on anorexia was demonstrated between the granisetron and non-granisetron group, indicating that control of alimentary symptoms such as nausea and vomiting influences the severity of anorexia. As to the safety, nausea was lengthened and deteriorated in one patients. Though the physician in charge judged it to be an adverse event too minor to question the safety of granisetron. Thus, granisetron proved to be highly effective and safe in preventing nausea, vomiting and anorexia in patients under concomitant administration of radiotherapy with hypertensor and arterial infusion of anticancer chemotherapies.
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PMID:[The preventive effect of granisetron on digestive tract symptoms induced by arterial infusion of anticancer and hypertensive agents in combination with radiotherapy--a study of forty patients with bladder cancer]. 771 15

A highly sensitive and selective high-performance liquid chromatographic method was developed for the determination of granisetron and its active metabolite, 7-hydroxygranisetron (7OH-G) in human plasma. Granisetron is a selective 5-hydroxytryptamine receptor antagonist used in the treatment of cytotoxic drug-induced emesis. The method involves isolation of granisetron, 7OH-G and the internal standards from plasma by solid-phase extraction prior to reversed-phase ion-pair chromatographic separation on an octyl silica column with subsequent quantification of analytes simultaneously either with electrochemical (7OH-G) or fluorescence (granisetron) detectors which are placed in series. The recovery of granisetron and 7OH-G from human plasma was quantitative. Using 1 ml of plasma, the limits of quantification for granisetron and 7OH-G were 0.1 and 0.25 ng/ml, respectively. Linear responses in analyte/internal standard peak-area ratios were observed for analyte concentrations ranging from 0.1 to 50 ng/ml plasma. Precision and accuracy were within 13% across the calibration range for both granisetron and 7OH-G. The method was sufficiently sensitive, accurate and precise to support pharmacokinetic studies for granisetron and 7OH-G, in both normal and patient populations.
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PMID:Simultaneous determination of granisetron and its 7-hydroxy metabolite in human plasma by reversed-phase high-performance liquid chromatography utilizing fluorescence and electrochemical detection. 771 53

Postoperative nausea and vomiting are common after recovery from anesthesia. We examined the prophylactic effect of granisetron on postoperative nausea and vomiting in 120 female patients (ASA physical status I) undergoing gynecologic surgery. They were randomly allocated to one of three groups (n = 40 for each): saline (as a control), granisetron 20 micrograms/kg, and granisetron 40 micrograms/kg. Saline or granisetron was given intravenously (IV) over 5 min approximately 30 min before the end of anesthesia. Nausea, vomiting, and safety assessments were performed during the 24-h recovery period. For the 24-h period after surgery, the number of emesis-free patients was significantly larger in the granisetron groups than in the control group (83%, 78%, and 20% of patients receiving granisetron 20 micrograms/kg and 40 micrograms/kg, and saline, respectively). Granisetron at both doses also was superior to the control for the prevention of nausea over the 24-h study period (nausea visual analog scales at 24-h postsurgery: 49 mm, 17 mm, and 18 mm in the control, granisetron 20 micrograms/kg, and granisetron 40 micrograms/kg groups, respectively). Fewer patients received "rescue" antiemetics in the granisetron groups than in the control group (10%, 10%, and 43% of patients in granisetron 20 micrograms/kg and 40 micrograms/kg, and the control groups, respectively). The adverse events in the granisetron groups were similar to those in the control group. The administration of granisetron had no significant effect on vital signs or clinical laboratory test profiles. Granisetron given at 20 or 40 micrograms/kg i.v. during anesthesia appears to be a simple, effective, and safe method for preventing postoperative nausea and vomiting.
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PMID:The antiemetic efficacy of prophylactic granisetron in gynecologic surgery. 772 41

The antiemetic efficacy of a combination of granisetron and clonazepam was investigated in 39 gynecological cancer patients treated with cisplatin. Granisetron (3 mg/body/day) was administered by intravenous drip infusion before and 24 hours after anticancer drug administration, and clonazepam was taken orally twice a day. With a combination of granisetron and clonazepam, excellent efficacy was found in 87% (34/39) of the cases. Delayed emesis occurred in 38% (13/34), but the degree of nausea was mild. Clinically, antiemetic therapy with a combination of granisetron and clonazepam demonstrated superior antiemetic effects and seems to be useful for controlling nausea and vomiting associated with cancer chemotherapy.
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PMID:[The prevention of cancer chemotherapy-induced emesis with granisetron and clonazepam]. 785 98

From December 1991 to September 1992, 20 patients due to receive total body irradiation (TBI) prior to allogenic or autologus bone marrow transplantation were given granisetron (Kytril) in order to prevent intestinal (nausea and vomiting) early intolerance. TBI regimen was delivered on a fractional basis of six fractions, over 3 days. Twelve grays were delivered with a lung protection decreasing the pulmonary dose to 9 Gy. Granisetron (3 mg) was administered by a 5-min intravenous infusion, 1 h before TBI. Up to two further infusions were given if nausea or vomiting occurred. The pretreatment perfusion was sufficient to prevent nausea and vomiting in 10/20 patients, one additional post-treatment perfusion was necessary in 7/20 patients, and two in 1/20 patients. In 2/20 cases, nausea and vomiting persisted in spite of three perfusions. Excellent or good efficacy was noted in 15/20 patients and a minor (or no) efficacy in five. Granisetron appears to be superior to the conventional anti emetic schemes to prevent nausea and vomiting in patients receiving TBI for bone marrow transplantation.
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PMID:[Value of granisetron in the prevention of digestive disorders in total body irradiation]. 789 22

This review discusses the development and use of 5-hydroxytryptamine3 (5-HT3) antagonists, especially granisetron, for the treatment of chemotherapy-induced emesis. Following recent evidence suggesting that high-dose chemotherapy is more effective in increasing tumor response rate and median survival time, more effective antiemetic control is essential. Granisetron, a new 5-HT3, is approximately 400 times more potent than metoclopramide and, unlike metoclopramide, does not produce extrapyramidal side effects. Granisetron has been shown to be effective as a single prophylactic dose, over 5 days and in patients receiving repeated cycles of chemotherapy. Patients with nausea and vomiting within the first 24 h after chemotherapy are more likely to experience delayed symptoms; however, episodes of breakthrough nausea and vomiting can be controlled by intervention with one, and in some cases more, doses of granisetron. The development of granisetron represents an important advance in the control of chemotherapy induced emesis.
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PMID:Clinical experience with intravenous granisetron. 791 51


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