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)

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.
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PMID:The anti-emetic efficacy and tolerability of tropisetron in patients conditioned with high-dose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation. 808 43

The efficacy of Granisetron, a new and selective 5HT3-receptor-antagonist in the treatment of cytostatic induced emesis, was tested in the department of gynaecology and obstetrics of the University of Essen on 77 patients. The patients received cytostatic drugs with a high emetogenic potency (for example cisplatin) or with a moderately high emetogenic potency (for example cyclophosphamide). We were able to demonstrate the high antiemetic efficacy of Granisetron. We had in 63% of the cases a "complete response" during the first 24 h after the chemotherapy and a "complete response" of 60% for the "delayed emesis". The observed adverse reactions such as constipation and headache were easily solved with standard laxatives or standard analgesics. Because of the high efficacy of Granisetron, which was combined with a low rate of side effects, it was possible to give to all the 77 patients the complete and necessary chemotherapy, so that no patient refused to receive the chemotherapy just because of nausea or emesis. The use of Granisetron is therefore a major step forward in the care of patients receiving chemotherapy because nausea and emesis can be treated effectively.
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PMID:[Granisetron, a new and potent antiemetic for treatment of cytostatic drug-induced vomiting in gynecological malignancies]. 815 Feb 51

Tropisetron is a novel, potent and highly selective 5-HT3 receptor antagonist, which is active in the treatment of nausea and vomiting induced by highly emetogenic chemotherapeutic drugs such as cisplatin. Tropisetron selectively blocks the excitation of the presynaptic 5-HT receptors of the peripheral neurones involved in the emetic reflex, and may have other direct actions in the CNS on 5-HT3 receptors, mediating the actions of vagal inputs to the area postrema. Toxicological studies show that tropisetron is generally well tolerated by all animal species investigated and no specific organ toxicity was observed, other than slight loss of body weight development. In man, tropisetron metabolism is linked to the cytochrome P-450 2D6 isoenzyme system, which determines the polymorphism of debrisoquine/sparteine metabolism. As a result, there are phenotypical populations of extensive and poor metabolizers. The two main adverse events in human volunteer tolerability studies with tropisetron were headache and constipation. These adverse events tended to be slightly more intense and to last longer in poor metabolizers, compared with extensive metabolizers. Tropisetron had similar pharmacokinetic characteristics in elderly patients and renal patients, compared with healthy subjects. From a toxicological and pharmacokinetic point of view, therefore, daily doses of 5 mg tropisetron can be administered to both poor and extensive metabolizers, as well as to special populations, without any particular precautions.
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PMID:Pharmacology, toxicology and human pharmacokinetics of tropisetron. 836 93

This state-of-the-art review describes the development, over the past 12 years, of new agents for the control of chemotherapy- and radiotherapy-induced emesis. While the mechanism of chemotherapy-induced nausea and vomiting is still not fully understood, significant progress in prevention of the symptoms has been achieved. The discovery that high-dose metoclopramide was very effective in antiemetic control ultimately led to the development of a new class of antiemetics, the 5-HT3 receptor antagonists, of which tropisetron is the most recent to be introduced. The emphasis of the review is on acute chemotherapy-induced emesis and includes current thinking on the influence of patient characteristics on the emetic outcome. The new 5-HT3 receptor antagonists do not demonstrate any of the distressing extrapyramidal reactions so frequently encountered with conventional antiemetics acting at dopamine receptor sites. Mild headache is the most characteristic side effect of this class of agents. The major advantages of the newer 5-HT3 receptor antagonists, such as tropisetron, over the conventional antiemetic regimens are convenience, flexibility and, above all, single-dose usage.
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PMID:Current issues in the management of nausea and vomiting. 836 96

An open, two-armed, multicentre trial was conducted in 231 patients with malignant disease who had previously failed to respond to conventional antiemetic treatment for the prevention of chemotherapy-induced nausea and vomiting. Patients were randomized to receive either tropisetron (5 mg/day; n = 115) or a standard antiemetic therapy, which was considered optimal for each individual but did not include a 5-HT3 receptor antagonist (n = 116). Acute vomiting on Day 1 was controlled in 60 (52%) tropisetron patients, compared with only 29 (25%) patients receiving optimal standard therapy (p < 0.001). Acute nausea was completely inhibited in 37 (32%) tropisetron patients, compared with 22 (19%) patients on optimal standard therapy (p < 0.05). On Day 1, delayed vomiting was also significantly better prevented by tropisetron (p < 0.001). Side effects from tropisetron (headache and constipation) were mild, and no extrapyramidal symptoms were observed in any tropisetron patients, in contrast, to 14 (13%) patients in the 'optimal standard' group. In conclusion, in cases of acute nausea and vomiting it is more effective to switch refractory patients to tropisetron rather than attempt to optimize the dose of standard antiemetic therapy. For delayed nausea and vomiting, combination antiemetic therapy, with differing types of receptor antagonism and corticosteroids may provide the best way forward. Such studies are in progress.
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PMID:Tropisetron in the prevention of chemotherapy-induced nausea and vomiting in patients responding poorly to previous conventional antiemetic therapy. 836 95

An open, non-comparative, Nordic multicenter study was performed during 1991-1992 to evaluate the new 5-HT3 receptor antagonist tropisetron, as an antiemetic agent in various types of cancer chemotherapy. More than 600 patients were recruited from 16 cancer centers in Sweden, Finland and Denmark. In this report an interim analysis on 231 patients is presented. Gynecological cancers (61%), lung cancer (14%) and breast cancer (7%), were the main diagnoses. In 118 of 231 patients (51%) prior experience of chemotherapy was documented. In 91 patients (39%) cisplatin was part of the cytostatic regimen. Carboplatin (27%), doxorubicin (32%), epidoxorubicin (18%) were also frequently included. In all, 18 cytostatic agents were studied. The median number of courses studied was 3.3 (range 1-15). Overall 153 of 231 patients (67%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting (Days 2-6) were completely controlled in 45%-72%. Treatment efficacy remained stable (57%-89%) over 10 consecutive courses of chemotherapy. For non-cisplatin regimens complete protection was achieved in 78% compared with 51% for cisplatin-regimens (p < 0.0001). Patients with no prior experience of chemotherapy had greater control of acute nausea and vomiting (73%) than patients treated before (61%) in the first course, but not in subsequent courses. There were no such differences in control of delayed nausea and vomiting between chemotherapy-naive and previously treated patients. Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%-36% of the cases during long-term follow-up. Headache (16%) and constipation (5%) were most frequent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tropisetron in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. 836 99

The anti-emetic efficacy and safety of granisetron, a highly selective and potent 5-HT3 receptor antagonist, was compared with that of high-dose metoclopramide plus dexamethasone in 281 patients due to receive single-day cisplatin chemotherapy (> or = 49 mg m-2). In this single-blind, multicentre study, granisetron (40 micrograms kg-1) was administered as a single prophylactic 5-min infusion. Dexamethasone (12 mg) was administered as a 30-min infusion followed by a loading dose of 3 mg kg-1 metoclopramide. A maintenance dose of metoclopramide 4 mg kg-1 was then infused over 8 h. A single prophylactic dose of granisetron was as effective as the combination regimen in the prevention of cisplatin-induced emesis. Of 143 granisetron-treated patients, 100 (70%) were complete responders (no vomiting and no or only mild nausea) compared with 93/138 (67%) patients who received the comparator regimen. Twenty-three percent of granisetron-treated patients experienced one of more adverse events compared with 33% of patients in the comparator group. No extrapyramidal reactions were reported in the granisetron group compared with 13 in comparator-treated patients (8%). This difference was significant (P < 0.05). The commonest adverse event in the granisetron group, headache (9.8%) described by the majority of patients as mild, was significantly higher than that reported in the comparator group (3% P = 0.02). Granisetron appears to be a safe and effective agent which can be used as a single agent for the prophylaxis of cisplatin-induced emesis. The simplicity of administration, a single 5-min infusion prior to chemotherapy, and the lack of somnolence or extrapyramidal reactions offer clear advantages over the comparator combination regimen.
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PMID:The control of acute cisplatin-induced emesis--a comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone. Granisetron Study Group. 839 4

Nausea and vomiting are among the most frequent and severe acute side-effects of cytotoxic therapy and are not optimally controlled by conventional antiemetics. This situation warrants the evaluation of new classes of antiemetic agents such as the 5-HT3 receptor antagonists. 19 children with a median age of 9 years (range 2-16 years), treated with cytotoxic drug combinations that had previously caused nausea and vomiting refractory to conventional antiemetics, were given the selective 5-HT3 receptor antagonist ICS 205-930. The drug was given intravenously (i.v.) at 0.2 mg/kg (maximum 5 mg) during the chemotherapy infusion period and was continued orally for up to 5 days in chemotherapy courses containing cisplatin. The number of emetic episodes was recorded and the response was scored according to following scale: grade 1 = no nausea, no emetic episode; grade 2 = up to four episodes of vomiting and less than 5 h of nausea; grade 3 = five or more than five emetic episodes and/or nausea for at least 5 h. The 19 patients received a total of 169 various courses of chemotherapy combined with ICS 205-930. A score of 3 was observed during one course only, a score of 2 in 37 out of the 169 courses, including the four courses with cisplatin. The drug was very well tolerated. Side-effects possibly related to ICS 205-930 were mild to moderate headache in 4 patients during seven courses overall and obstipation in 3 patients during 11 courses. The results strongly suggest that ICS 205-930 is a highly effective and safe antiemetic agent in non-naive pediatric patients receiving non-cisplatin cytotoxic chemotherapy and who had failed conventional antiemetic treatment.
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PMID:Prevention of emesis by ICS 205-930 in children receiving cytotoxic chemotherapy. 848 76

Intravenous 5-hydroxytryptamine3 (5-HT3) receptor antagonists are now established antiemetics in the treatment of chemotherapy-induced emesis. For optimal convenience and acceptability, oral therapy is desirable. Retrospective comparisons indicate that oral granisetron may have an efficacy comparable with that of intravenous granisetron. Recent new data are available on the use of granisetron in the prophylaxis of acute emesis in randomized, double-masked trials. After moderately emetogenic chemotherapy, the optimal regimen appears to be 1 mg twice daily, although 2 mg once daily is equally effective. Oral granisetron is significantly superior to oral prochlorperazine. After high-dose cisplatin chemotherapy, oral granisetron is as effective as metoclopramide plus dexamethasone; the addition of dexamethasone further enhances its efficacy. Oral granisetron was well tolerated in all these trials. Headache and constipation were the most common adverse events, as has been reported for other 5-HT3 receptor antagonists. No randomized trials of oral-only tropisetron or dolasetron have yet been published.
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PMID:Comparative efficacy of oral and intravenous granisetron for the prevention of acute chemotherapy-induced emesis. 887 88

Efficacy and safety of the antiemetic agent Navoban (5HT3-receptor-antagonist Tropisetron) on cytostatic-induced emesis of breast cancers and gynecological cancers was tested in 28 female patients receiving a total of 127 chemotherapy courses containing high (cisplatin), moderate high (cyclophosphamid) or moderate (for example 5 FU) emetogenic cytostatic drugs. We studied antiemetic response rates of Navoban (5 mg/d) during the first 24 hours after administration of the chemotherapy as well as response rates of the "delayed nausea and emesis" (days 2-9 after chemotherapy). A complete response was observed in 103 chemotherapy courses (= 81.1%) during the first 24 hours after chemotherapy and in 93 courses (= 73.2%) for the "delayed emesis". Treatment failures (more than 5 vomiting episodes) during the first 24 hours were present in four courses and for the "delayed emesis" in 11 courses. The side effects of Navoban such as constipation, headache or tiredness were minimum. Therefore no patient refused to receive the necessary chemotherapy. Navoban is, with its single dose application, an effective therapeutic drug for the prevention of nausea and emesis in patients receiving a chemotherapy.
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PMID:[Effectiveness and tolerance of Navoban (5HT3-receptor antagonist tropisetron) in prevention of cytostatic drug-induced nausea and vomiting in patients with breast carcinomas and gynecological malignancies]. 890 Jun 4


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