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)

Nausea and vomiting induced by anticancer agents are common problems associated with chemotherapy for cancer. Recent trials have examined a variety of antiemetics, representing several different classes of drugs. High dose metoclopramide provided the impetus for many of the current studies because of its effect against cisplatin induced vomiting. However, current regimens are not yet entirely effective in many patients receiving cisplatin or other highly emetogenic anticancer agents. A promising new class of antiemetics, 5-hydroxytryptamine receptor antagonists are undergoing clinical evaluations. Members of this class are easily and safely administered to patients receiving cisplatin or other emetogenic anticancer agents. These are highly active antiemetics, both prophylactic and interventional treatment. Lack of extrapyramidal reaction and other adverse effects associated with its use makes the drug a very attractive one. However, studies of antiemetics require consideration of methodologic issues that may not be of concern in trials of anticancer agents. The results of these studies can be affected by the patient population, the sample size, pharmacologic variables, the trial design, the method of analysis, etc. Recently, developments both in new-antiemetics and better ways of using the existing ones, lead us to cautious thought that nausea and vomiting due to cancer chemotherapy can be controlled substantially with benefit to the patients.
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PMID:[Antiemetics and its clinical evaluations]. 154 57

Three antiemetic compounds (zacopride, batanopride, granisetron [BRL43694]) were evaluated for the production of gastrointestinal side effects in the conscious ferret after i.v. or p.o. administration. Zacopride evoked multiple emetic and defecatory responses at clinically relevant doses (0.003-0.3 mg/kg) and in a dose-dependent manner. The oral route was the more potent one for eliciting emesis (ED50 0.033 mg/kg). At 0.3 mg/kg p.o., zacopride reliably evoked an 80 to 100% incidence of emesis and a 40 to 80% incidence of defecation. In contrast, batanopride and BRL43694 i.v. evoked a small (10%) incidence of these side effects, but only at 0.1 to 10 mg/kg doses. When given p.o. (0.00003-10 mg/kg), these latter compounds never evoked emesis and significantly reduced (P less than .05) the incidence of defecation below that of vehicle. Responses to zacopride (0.3 mg/kg p.o.) were challenged by i.p. pretreatment with the 5-hydroxytryptamine receptor agonist 2-methyl serotonin, the 5-hydroxytryptamine receptor antagonist BRL43694, the quaternary atropine derivative glycopyrrolate, the dopamine receptor antagonist domperidone or selective abdominal vagotomies. All compounds and either bilateral or dorsal vagotomy significantly reduced the incidence of emesis, but did not abolish it. Latency to first emesis was delayed by BRL43694, domperidone or dorsal vagotomy. The data suggest that the emetic response to p.o. zacopride is mediated in part by 5-hydroxytryptamine receptors residing on either enteric neurons or vagal afferents. However, the underlying pharmacology of the response may also include activation of cholinergic and dopaminergic pathways.
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PMID:Emesis and defecations induced by the 5-hydroxytryptamine (5-HT3) receptor antagonist zacopride in the ferret. 216 43

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

1. The effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOl), a 5-hydroxytryptamine 5-HT2A/5-HT2C receptor agonist, on motion- and cisplatin-induced emesis were studied in Suncus murinus. Subcutaneous injection of DOl, 30 min prior to the emetic stimuli, dose-dependently blocked the emesis induced by motion sickness and cisplatin (20 mg kg-1, i.p.) with estimated ID50 values of 640 and 780 micrograms kg-1, respectively. 2. alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT), a peripheral 5-HT2A/5-HT2C receptor agonist, had no effect on motion- and cisplatin-induced emesis. 3. The antiemetic effects of DOl on motion- and cisplatin-induced emesis were attenuated by preadministration of ketanserin, a selective 5-HT2A receptor antagonist. 4. The present results suggest an inhibitory role for central 5-HT2 receptors in the emetic reflex mechanism and that a 5-HT2 receptor agonist may be a useful tool to investigate the involvement of 5-HT receptors in the emetic reflex.
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PMID:Blockade of motion- and cisplatin-induced emesis by a 5-HT2 receptor agonist in Suncus murinus. 778 Jun 47

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT3) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%-98% and 77%-93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect followed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.
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PMID:Control of emesis by intravenous granisetron in breast cancer patients treated with 5-FU, epirubicin and cyclophosphamide. 803 7

The Fusarium mycotoxin deoxynivalenol (DON) is a potent emetic agent. While the basic mechanisms which invoke and mediate emesis are still poorly understood, various neurotransmitters appear to be involved. The action of these transmitters can be blocked by various receptor-specific antagonists. The current study investigated the efficacy of several classes of receptor antagonists to block the emetic effect of DON. Following anti-emetic pretreatment, pigs were administered the toxin (i.v., 80 micrograms/kg, or oral, 300 micrograms/kg) and the onset of emesis was monitored. Certain specific serotonin (5HT3)-receptor antagonists (ICS 205-930, BRL 43694 A) were found to efficaciously prevent DON-induced vomiting. These observations support the hypothesis that serotonin plays an important role in chemically induced emesis. Also moderately effective, but requiring high doses, were the 5HT2-receptor antagonists, cyproheptadine and sulpiride. A variety of compounds possessing strong anticholinergic activity were also efficacious. These, however, apparently act directly at the emetic center and thus are capable of preventing emesis regardless of the cause, including chemically induced vomiting. Non-effective were the antihistaminic and antidopaminergic anti-emetics; except, those which also possessed considerable anticholinergic activity, and i.v. administered chlorpromazine which has been speculated to block specific receptors found in the brain's chemoreceptor trigger zone (CTZ) reportedly involved in initiating emesis.
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PMID:The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine. 816 50

Ondansetron is a 5-hydroxytryptamine receptor antagonist which has shown activity in the prevention of emesis following cytotoxic and radiation therapy for cancer. We describe our experience using ondansetron in 25 patients undergoing fractionated total body irradiation (TBI) 12 Gy/3 days as conditioning for bone marrow transplantation. Antiemetic efficiency was investigated during the 3 days of TBI prior to high-dose cytotoxic chemotherapy. Twenty-two of the 25 patients (88%) achieved sufficient emesis control with less than three emetic episodes whereas the remaining 12% experienced three to five emetic events during their worst 24-h period. Eleven patients (44%) had complete control with no vomiting at all. Of 75 'patient days', 52 (69%) were without any emesis, 20 (27%) were associated with one to two and only three (4%) with three to five emetic episodes. Headache occurred in four patients (16%). No other significant adverse effects were seen, in particular no extrapyramidal reactions due to ondansetron. Our data confirm that ondansetron plays a major role in the antiemetic management of patients undergoing TBI.
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PMID:Ondansetron for efficient emesis control during total body irradiation. 820 86

This report of a double-blind, randomized study performed to evaluate the comparative antiemetic efficacy of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), a new 5-hydroxytryptamine receptor antagonist, focuses on treatment during stages of chemotherapy when nausea and vomiting are particularly severe. One hundred fifteen chemotherapy-naive patients with malignant disease were administered either tropisetron (n = 58) or a dexamethasone dose plus a metoclopramide dose (n = 57) during 5 days of two successive cycles of chemotherapy. Within the first 24 hours after receiving cisplatin-based chemotherapy, 76% of patients in the tropisetron group remained free of vomiting (with 59% of patients free of nausea) compared with 39% of patients free of vomiting in the conventionally treated group (30% of patients free of nausea). Improved control of emesis also was observed over 4 consecutive days of follow-up in the tropisetron group. The difference in incidence of nausea and vomiting between the patient groups was statistically significant (P < .05). The efficacy of tropisetron was well maintained during the second consecutive chemotherapy cycle; during the first 24 hours, 72% and 62% of patients remained free of vomiting and nausea, respectively. Tropisetron appears to be a highly effective, well tolerated, and simple to use antiemetic agent for patients receiving chemotherapy.
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PMID:A report comparing the use of tropisetron (Navoban), a 5-HT3 antagonist, with a standard antiemetic regimen of dexamethasone and metoclopramide in cisplatin-treated patients under conditions of severe emesis. 911 19

Emesis is one of the most frequent and distressing adverse effects of cytotoxic chemotherapy. Conventional antiemetic regimens are unsatisfactory due to their poor efficacy and their adverse events, particularly in children. Tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) belongs to a new class of 5-hydroxytryptamine receptor antagonists with antiemetic effectiveness in patients receiving anticancer agents. We evaluated tropisetron (0.2 mg/kg/d) in 24 chemotherapy-treated children who had experienced severe emesis during previous chemotherapy courses in spite of concomitant administration of either alizapride or metoclopramide. Complete control of emesis was achieved in 70% of the courses (37% of those including cisplatin). No severe adverse effect was reported. Headache was observed in two courses and constipation was observed during two other courses. Tropisetron proved clearly superior to conventional antiemetics and safe in use.
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PMID:Prevention of emesis by tropisetron (Navoban) in children receiving cytotoxic therapy for solid malignancies. 911 22

Several serotonin (5-HT) receptor subtypes have been defined by pharmacological responses to selective agonists and antagonists and by pathways of receptor-effector coupling. Using molecular techniques, additional receptor subtypes have been described. 5-HT receptors are prevalent in the central nervous system and gut and participate in induction of emesis. 5-HT3 antagonists are used to prevent emesis from cancer chemotherapy and also demonstrate efficacy in radiation-induced nausea, postoperative nausea, hyperemesis gravidarum, and nausea and vomiting with the acquired immunodeficiency syndrome. 5-HT4 agonists exhibit prokinetic properties in nauseated patients with gastroparesis and functional dyspepsia. Conversely, 5-HT4 antagonists have antiemetic activity in some experimental models. The 5-HT1D receptor agonist sumatriptan reduces emesis with migraine headaches and in cyclic vomiting syndrome, most likely via action on central nervous system sites. In other models, 5-HT1A and 5-HT2A/5-HT2C agonists exhibit antiemetic properties. The utility of 5-HT receptor ligands in treating emesis is the subject of active investigation.
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PMID:Serotonin receptor physiology: relation to emesis. 1049 49


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