Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ondansetron was compared with metoclopramide for antiemetic efficacy in a randomised double-blind trial in 122 patients with advanced breast cancer. All patients were treated with epirubicin (greater than 50 mg/m2) and cyclophosphamide (greater than 500 mg/m2). 50 patients receiving ondansetron and 60 with metoclopramide were considered evaluable. Ondansetron was at least as effective as metoclopramide in the control of vomiting and nausea. The percentage of patients with complete plus major control was 72% (59-85%) vs. 61% (48-74%) on day 1 (P = 0.230) and 79% (67-91%) vs. 66% (53-78%) on days 2-3 after chemotherapy (P = 0.122). Over the 3-day study period, nausea was absent or mild in 60% of the patients treated with ondansetron, compared to 45% given metoclopramide (P = 0.064). No major drug-related side-effects were reported. 1 patient receiving ondansetron experienced gastrointestinal disturbance and headache. Episodes of diarrhoea, fever, hyperkinetic syndrome, fatigue, restlessness and migraine with vomiting were reported by 5 patients treated with metoclopramide. None of the changes in the biochemical or haematological parameters was attributed to the antiemetic treatments.
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PMID:Double-blind randomised trial of the antiemetic efficacy and safety of ondansetron and metoclopramide in advanced breast cancer patients treated with epirubicin and cyclophosphamide. 183 24

Serotonin (5-Hydroxytryptamine) seems to play a dominant role in triggering vomiting induced by cytotoxic agents through the stimulation of 5-HT3 receptors. They have been observed in the GI tract as well as in the brain (area postrema). Ondansetron is a specific antagonist of 5-HT3 serotonin receptors. Its anti-emetic activity is very powerful in the ferret. The availability of an injectable or oral form of this product allows the overall treatment of acute and delayed emesis and its administration is in accordance with different schedules: single IV injection or a continuous 24 hour infusion or repeated IV injection followed by oral treatment. The pharmacokinetics of the drug are as follows: absorption begins about 30 minutes after the administration per os, its biodisponibility is about 60%, its clearance: 20 ml/minute and its elimination half life about 3 hours. Different double blind studies, carried out in parallel groups or in cross over, demonstrated the superiority of ondansetron over metoclopramide in the control of nausea and vomiting, whether or not the chemotherapy contained cisplatin; a more recent study shows also that ondansetron was superior to alizapride and methylprednisolone in combination. Side effects of ondansetron do not include extrapyramidal symptoms but only headaches and constipation. The use of ondansetron improves the well-being of patients receiving chemotherapy and increases protocol compliance.
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PMID:[Ondansetron: a specific 5-HT3 serotonin receptor inhibitor, a new antiemetic in oncology]. 183 90

Thirty four patients who were receiving carboplatin 400 mg/m2 for advanced epithelial ovarian cancer were treated with ondansetron antiemetic prophylaxis. Ondansetron was given as 4 mg oral +4 mg iv 30 minutes prior to carboplatin followed by 8 mg oral tds for 5 days. Of the evaluable patients complete or major control of emesis on day one was achieved in 94% of previously untreated patients and 81% of patients refractory to conventional antiemetic therapy. For the 5 day period as a whole 88% of untreated patients and 69% of those with refractory emesis reported complete or major control of nausea and vomiting. Fifteen patients noted no side effects with mild headache (30%) and constipation (21%) the most frequent problems in the remainder. Ondansetron is effective antiemetic prophylaxis for carboplatin chemotherapy and should allow the majority of these patients to be managed on an out-patient basis.
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PMID:A phase II study of ondansetron as antiemetic prophylaxis in patients receiving carboplatin for advanced ovarian cancer. The North Thames Ovary Group. 183 30

Nausea and vomiting are serious problems for patients receiving cancer chemotherapy. Dopamine receptor and cholinergic receptor antagonism have been the target mechanism for agents used to combat drug-induced nausea and vomiting; more recently, blockade of serotonin receptors has been used for this indication. Current therapies are limited by extrapyramidal adverse effects, as well as drowsiness, sedation, respiratory depression, and cardiac effects. Ondansetron is an investigational serotonin antagonist that has documented effectiveness for cancer chemotherapy-induced emesis. Ondansetron appears to be well tolerated, with the possible exception of headaches and transient increases in liver enzymes. No extrapyramidal toxicities have been reported with this agent. While ondansetron looks promising, further studies are needed to fully define its role as an antiemetic.
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PMID:Ondansetron: a new entity in emesis control. 214 59

Emesis in chemotherapy containing Cisplatinum (DDP) is still a therapeutical dilemma. Emesis and nausea cause the cessation of a potential curative therapy in up to 10% of patients treated with DDP. We studied the antiemetic effectiveness of the selective Serotonin (5HT3)-receptor-antagonist Ondansetron (GR 38032F, Glaxo) in patients receiving high dose platinum chemotherapy. All patients suffered from severe emesis and were refractory to any standard antiemetic regimen (Metoclopramid). We studied the efficacy of the new drug against acute and delayed emesis following platinum chemotherapy. All adverse events are listed. Thirty four courses (n = 17 patients) of a platinum-containing regimen were analyzed so far. A sufficient antiemetic efficacy was observed in 56% of the courses. In 32 of 34 course (94%) the patients preferred the new drug compared with the standard antiemetic regime (Metoclopramid). In most cases only minor adverse events--which do not require any medical therapy--occurred. The most common adverse events were headache, constipation, dry mouth, abdominal discomfort and elevation of liver enzyme level without any clinical symptoms. One patient needed bowel surgery for severe constipation based on widespread intra-abdominal carcinosis.
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PMID:[Refractory vomiting with cisplatin therapy. Prospective study with the serotonin receptor antagonist GR 38032F]. 215 May 51

In an open, drug-oriented phase-II/III-study 24 patients were treated with the 5-HT3-antagonist Ondansetron as an antiemetic drug for chemotherapy-induced nausea and emesis. Patients with treatment regimen containing cisplatin were excluded. All patients had suffered from severe nausea and vomiting under conventional antiemetic drugs during a previous identical chemotherapy cycle and were treated with 8 mg Ondansetron t.d. on the day of the chemotherapy and on the four following days. The drug was given with 90 cytostatic cycles ranging from 1 to 14 cycles per patient. Only 2 patients (8%) did not experience an improvement of their symptoms in any of the treatment cycles as measured by a self-conducted grading of nausea and by the frequency of vomiting in comparison to a previous treatment cycle under conventional antiemetic therapy. Eleven out of 18 patients, who were treated with Ondansetron more than once (61%) noted a diminished frequency of vomiting in each treatment cycle with Ondansetron. Sixty of the 90 therapy cycles with Ondansetron resulted in complete (no vomiting) or major (one to two vomits within 24 h following chemotherapy) protection from emesis (37 and 29 per cent, respectively). The most frequent side effect noted was obstipation (7 patients), followed by slight diffuse abdominal pain (4 patients, probably also due to chemotherapy) and slight to severe headache (3 patients, 1 patient was therefore withdrawn from the study). No other side effects were seen. In conclusion, our study indicates that Ondansetron is an effective and safe drug for the treatment of cytostatic drug-induced nausea and vomiting.
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PMID:[Ondansetron (GR 38032F), a competitive 5-HT3 receptor antagonist as an antiemetic in cytostatic drug-induced nausea and vomiting. An open, substance-oriented phase II/III study]. 215 May 52

Ondansetron is a 5-HT3 receptor antagonist which has shown activity in the prevention of nausea and vomiting resulting from cytotoxic therapy. This paper describes the results of studies evaluating the efficacy of oral ondansetron in controlling radiation-induced emesis. Initial non-randomised studies showed that doses of 4 mg q.d.s. or 8 mg t.d.s. of ondansetron achieved complete or major control of vomiting in 77-91% of patients and mild or absence of nausea in 72-77% following single exposure high-dose (8-10 Gy) radiotherapy to the upper abdomen. A subsequent double-blind, prospective, randomised trial compared ondansetron 8 mg t.d.s. with metoclopramide 10 mg t.d.s. in the prevention of emesis following single radiation doses of 8-10 Gy to the upper abdomen. On the day of radiotherapy, ondansetron achieved significantly greater control of vomiting and retching (P less than 0.001) and nausea (P = 0.001) than metoclopramide. An advantage for ondansetron was also seen on days 2 and 3 after irradiation, although this did not reach a statistically significant level. Only two patients, out of 154, in all the studies experienced side effects attributable to ondansetron: one developed headache and the other experienced headache and vertigo. These studies show that ondansetron is a safe drug, with activity in the prevention of radiation-induced emesis and significantly greater efficacy than metoclopramide in the control of nausea and vomiting following single exposure upper abdominal high-dose radiotherapy.
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PMID:Clinical studies with ondansetron in the control of radiation-induced emesis. 253 96

We investigated the antiemetic efficacy and safety of intravenous ondansetron infusion in the BMT setting. We conducted prospective randomized comparison trials between ondansetron at 2 dose levels and metoclopramide (MCP) plus droperidol for the prevention of chemotherapy-induced nausea and vomiting in 2 patient populations scheduled to undergo BMT. One patient population (n = 30) received CY alone, the other population (n = 30) received combination chemotherapy of Bu and CY. The CY alone group received ondansetron for 3 days, and the Bu/CY group received ondansetron for 7 days. The primary endpoints were emesis control and nausea. Secondary endpoints included acute (headache, diarrhea and sedation) and delayed (engraftment and regimen-related) side-effects. In both trials, ondansetron provided better emesis control than did MCP plus droperidol during CY administration (P = 0.009, 3-day trial; P = 0.0022, 7-day trial). There was a wide interpatient variation in serum ondansetron levels, although group averages were proportional to the dose administered. Intrapatient day-to-day variation was 10-30% and did not change significantly with concurrent CY administration. Antiemetic efficacy did not correlate with ondansetron serum levels at the doses tested. Headache incidence was similar in all groups. Sedation was highest in the MCP plus droperidol group (P = 0.048, 3-day trial; P = 0.016, 7-day trial). No statistically significant differences in engraftment or regimen-related toxicities were observed between groups in either trial. Ondansetron appears to be a safe and efficacious antiemetic during conditioning for BMT.
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PMID:Antiemetic efficacy and pharmacokinetics of intravenous ondansetron infusion during chemotherapy conditioning for bone marrow transplant. 758 Nov 39

The double-label flow cytometric analysis of peripheral serotonergic pathways of migraine and cluster headache on a monocyte model has been used to evaluate the activity of drugs with a selective activity on central vascular 5-HT1D receptors, such as sumatriptan, ergotamine and ondansetron. The results indicated that sumatriptan and ergotamine progressively increase the peripheral expression of 5-HT (5-hydroxytryptamine, serotonin). The increase obtained in migraine after ergotamine is more evident than that obtained in cases of cluster headache. Ondansetron produced a moderate increase in serotonergic expression only in cluster headache. The events that occur at intracranic neural and vascular level may cause the described changes of 5-HT expression on the monocyte model as an indirect, reflective, peripheral registration of central serotonergic variations during headache attack as well as during the drug-sustained recovery phase.
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PMID:Upregulated expression of peripheral serotonergic receptors in migraine and cluster headache by sumatriptan. 767 73

Ondansetron is a selective 5-HT3 receptor antagonist which has previously been reported in the Journal to be a promising new agent for use as prophylaxis against nausea and vomiting caused by chemotherapy and radiotherapy. Since the publication of this original review, further studies have been published that show ondansetron to be an effective antiemetic agent in patients receiving chemotherapy and radiotherapy. Several studies have shown ondansetron to be a more effective antiemetic agent than high-dose metoclopramide in patients with emesis induced by high- and low-dose cisplatin treatment, and noncisplatin chemotherapy-induced emesis. The drug as mono-therapy does not appear to offer any advantage over alternative therapies against delayed high-dose cisplatin-induced nausea and vomiting; however, extremely limited data suggest that ondansetron plus dexamethasone may be useful in this indication. Trials have shown combination therapy with ondansetron and dexamethasone to be significantly more effective than both ondansetron monotherapy and a standard antiemetic regimen comprising metoclopramide, dexamethasone and diphenhydramine against acute high-dose cisplatin-induced emesis. Results from a number of small scale trials suggest that ondansetron may be an effective treatment for chemotherapy-induced emesis refractory to conventional antiemetic therapy. Ondansetron also appears to be more effective against refractory emesis induced by noncisplatin chemotherapy than that induced by cisplatin chemotherapy. Several trials have shown ondansetron to be more effective than placebo as prophylaxis against postoperative nausea and vomiting; a further trial has shown single-dose ondansetron to be significantly more effective than single-dose droperidol or metoclopramide in this indication. In addition, several trials have shown ondansetron to be more effective than placebo as treatment for nausea and vomiting that has commenced postoperatively. The overall incidence of adverse events in ondansetron recipients during chemotherapy-induced emesis studies was 36%. Headache and constipation are the most common adverse events during ondansetron therapy. Thus, recent data affirms the efficacy of ondansetron in the treatment of acute chemotherapy-induced nausea and vomiting and shows it to be especially efficacious when combined with dexamethasone. It appears that the drug will also have a substantial role in the prophylaxis and treatment of postoperative nausea and vomiting.
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PMID:Ondansetron. An update of its therapeutic use in chemotherapy-induced and postoperative nausea and vomiting. 769


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