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

The availability of radiolabelled ligands selective for various putative neurotransmitter receptor sites and the development of quantitative autoradiography has led to a greater understanding of the neuronal pathway and receptor subtypes involved in the vomiting reflex induced by various mechanisms both within the central nervous system and the periphery. Receptors for acetylcholine, dopamine, histamine and serotonin have been detected in a number of brain regions associated with the vomiting reflex, and provide a rational basis for the antiemetic action of drugs that inhibit receptor subtypes for these neurotransmitters. The basis of the antiemetic action of other drugs such as dexamethasone and the cannabinoids is still obscure. Some drugs act on more than 1 receptor subtype. Metoclopramide may inhibit both dopamine D2- and 5-HT3 receptors in producing its antiemetic effect. Both metoclopramide and domperidone appear to have additional peripheral actions that contribute to their effectiveness. The cannabinoids are effective in cytotoxic-induced vomiting, perhaps acting via endorphin receptors or by inhibiting prostaglandin synthesis. The effectiveness of 5-HT3 receptor antagonists may depend on the block of both central and peripheral neuronal 5-HT3 receptors. Vomiting constitutes a major disadvantage to the use of many drugs; vomiting induced by aminoglycoside antibiotics appears to be due to ototoxicity and is relieved by histamine H1-receptor antagonists. The protracted vomiting associated with the use of some cytotoxics in cancer chemotherapy may involve psychic components, the chemoreceptor trigger zone and peripheral sensory neurons. Both 5-HT3 and dopamine D2-receptor antagonists exert some control, the former being more effective with cytotoxics of high emetogenic potential, such as cisplatin. Serotonin 5-HT3 receptor antagonists or high doses of metoclopramide in combination with anxiolytics and steroids as well as greater attention to pharmacokinetic profiles of the drugs involved would appear to offer improved control. The use of dopamine receptor antagonists in controlling emesis induced by dopamine agonists used in Parkinson's disease poses theoretical problems which can be overcome by using drugs with selectivity for the chemoreceptor trigger zone, such as domperidone or metoclopramide. However, higher doses of these drugs may produce some impairment of therapeutic responses to the agonists. Muscarinic and nicotinic agonists currently under investigation in Alzheimer's disease pose another therapeutic dilemma as emesis is due to a central action of these compounds. Several sites may be involved including the chemoreceptor trigger zone and frontal lobes. Opiates may act through dopamine receptors or mu-receptors on dopaminergic nerves, but serotonergic mechanisms may also be involved in the action of some opiates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Pharmacological agents affecting emesis. A review (Part I). 137 16

The metabolism of serotonin was studied in cancer patients of their first day of their first course of chemotherapeutic drugs either with strongly or moderately emetogenic regimens. It was observed that strongly emetogenic treatments induce greater increases in serotonin release than moderately emetogenic regimens. High-dose cisplatinum (75 +/- 5 or 83.8 +/- 5 mg m-2) produced a marked increase in the plasma levels and in the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA). Neither platelet nor plasma (platelet-free plasma) serotonin were significantly modified by high-dose cisplatinum. Dacarbazine (283 +/- 22 mg m-2), another strongly emetogenic agent, induced acute nausea and emesis paralleled by marked increases in the urinary excretion of 5-HIAA. Both for high-dose cisplatinum and dacarbazine, the increases in serotonin metabolism occurred with a similar time-course than those of vomiting, and lasted for a period of 4 to 8 h. Low-dose cisplatinum (30.8 +/- 3 mg m-2) as well as cyclophosphamide-based chemotherapies (520 +/- 30 mg m-2) produced very small increases in the urinary excretion of 5-HIAA. Platelet and plasma serotonin levels failed to increase in cyclophosphamide-treated patients. Octreotide, a long-acting somatostatin analog, did not inhibit the increase in urinary 5-HIAA and the nausea and vomiting produced by high-dose cisplatinum. These results suggest that for treatments that induce marked increases in serotonin release such as high-dose cisplatinum or dacarbazine: (a) the amount and time course of serotonin release induced by chemotherapeutic drugs determines the severity, time of onset and pattern of emesis observed; (b) platelet serotonin play no role in chemotherapy-induced emesis; (c) strongly emetogenic regimens release serotonin from enterochromaffin cells; and (d) intestinal release of serotonin is the consequence of the damage induced by the chemotherapeutic drugs on the gut mucosa.
Br J Cancer 1992 Jul
PMID:Changes in serotonin metabolism in cancer patients: its relationship to nausea and vomiting induced by chemotherapeutic drugs. 137 60

In a multicentre trial, 78 patients with a variety of malignancies, who had experienced insufficient control of emesis (greater than or equal to 3 episodes within 24 hours) while receiving standard antiemetics during previous chemotherapy, were randomly assigned to receive tropisetron 5mg once daily for 5 days or conventional antiemetic drugs. No attempt was made to standardise the conventional antiemetic treatment, which was given according to the usual practice of the participating institutions. Emesis was evaluated by counting emetic episodes and nausea by asking the patients to record on a diary chart the duration and severity of the nausea. Emesis was much better controlled with tropisetron than with standard drugs, complete control during the first 24 hours being achieved in 42% and 8% of patients, respectively, (p less than 0.001). Nausea was of significantly shorter duration (6.9 vs 10.3 hours; p less than 0.01) and was less severe (p less than 0.005) in the tropisetron group. The patients' overall assessment of treatment outcome was markedly better for tropisetron than for the standard antiemetic therapy. The superior efficacy of tropisetron was especially marked during the first 24 hours. For delayed nausea, no significant difference between treatments was seen. No serious adverse effects were observed.
 ...
PMID:Prevention of chemotherapy-induced nausea and emesis in patients responding poorly to previous antiemetic therapy. Comparing tropisetron with optimised standard antiemetic therapy. 138 Apr 29

The efficacy of tropisetron in the prevention of nausea and vomiting induced by chemotherapy of varying emetogenic potential was evaluated in 545 patients with a variety of malignancies who had either proved refractory to antiemetic treatment during previous chemotherapy courses or who were considered to be at high risk of nausea and vomiting. Tropisetron 5 or 10mg was administered intravenously just before chemotherapy, with the possibility of additional oral or intravenous doses on the day before chemotherapy and on 1 or more subsequent days. On day 1 of the first course of chemotherapy, a complete response (no nausea and no vomiting) was achieved in 62% of patients and a partial response (1 to 4 vomits and/or episodes of nausea) in 29%. Among the 325 patients who received a second course of chemotherapy, more than 80% of those with a complete response on day 1 of course 1 also had a complete response on day 1 of course 2; 37% and 26%, respectively, of patients with a partial response or failure (1 or more vomits and/or episodes of nausea) on day 1 of course 1 then had a complete response on day 1 of course 2.
 ...
PMID:Compassionate use of a 5-HT3-receptor antagonist, tropisetron, in patients refractory to standard antiemetic treatment. 138 Apr 30

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.
Cancer Chemother Pharmacol 1992
PMID:Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. 138 61

A total of 535 chemotherapy naive, hospitalised patients (263 male/272 female) scheduled to receive cisplatin (50-120 mg m-2)-containing regimens participated in a randomised, double-blind, parallel group study to evaluate the efficacy and safety of three intravenous dose schedules of ondansetron in the prophylaxis of acute nausea and emesis. One hundred and eighty two patients received a loading dose of 8 mg of ondansetron followed by a 24 h infusion of 1 mg h-1 (group 1); 180 and 173 patients received single doses of 32 mg (group II) and 8 mg (group III) respectively, followed by a 24 h placebo infusion. Complete and major control (less than or equal to 2 emetic episodes) of acute emesis was achieved in 74% of patients in group I, 78% in group II and 74% in group III. Seventy seven per cent of the patients in group I, and 75% of patients in groups II and III respectively experienced no or mild nausea during the 24 h observation period. A retrospective stratification of the efficacy data on the basis of patient gender showed the response rate in females to be significant lower (43% vs 67%; less than 0.001). Ondanestron was well tolerated; mild headache was the most commonly reported adverse event (11% of patients) with a similar incidence in the three groups of patients. In conclusion, a single intravenous dose of 8 mg of ondansetron given prior to chemotherapy is as effective as a 32 mg daily dose given as either a single dose of a continuous infusion in the prophylaxis of acute cisplatin-induced emesis.
Br J Cancer 1992 Jul
PMID:Comparison of the anti-emetic efficacy of different doses of ondansetron, given as either a continuous infusion or a single intravenous dose, in acute cisplatin-induced emesis. A multicentre, double-blind, randomised, parallel group study. Ondansetron Study Group. 138 45

A 33 year old man developed acute oliguric failure lasting 66 days, eight days after admission with multiple gun shot wounds. On day 99 after admission, serum calcium was elevated mildly at 2.54 mmol/l (normal range 2.1-2.5 mmol/l). Serum parathormone was undetectable. He was discharged soon afterwards. He presented again on day 164 with nausea, vomiting and blurred vision. Fundoscopy revealed an ischaemic retinopathy and extensive keratopathy. Serum calcium was 3.48 mmol/l and serum creatinine 262 umol/l (normal range 40-110 umol/l). Repeat parathormone was undetectable and there was no evidence of myeloma, sarcoidosis or malignancy. Following treatment with intravenous saline and frusemide, serum calcium fell to a nadir of 3.05 mmol/l. On day 168 an infusion of sodium clodronate 300 mg was given. Twenty-four hours later serum calcium was 2.65 mmol/l and 48 hours later calcium was 2.26 mmol/l. Normocalcaemia was maintained for 17 days and severe hypercalcaemia never recurred. This is the first report in which biphosphonates have been successfully used to treat hypercalcaemia following acute renal failure thus obviating the need for further dialysis.
 ...
PMID:Severe hypercalcaemia four months after acute oliguric renal failure--successful treatment with intravenous clodronate. 138 45

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose.
 ...
PMID:[Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs]. 138 76

Anti-emetic effects, safety and usefulness of Ondansetron given intravenously at 4 mg once daily for consecutive 3-5 days were investigated against nausea and emesis induced by non-platinum anticancer drugs. Efficacy rates in control of nausea and emesis were 59% (20/34 cases) and 68% (23/34 cases), respectively. The efficacy rate for inhibition of nausea and emesis, calculated based on the control of nausea and emesis, was 68% (23/34 cases). Adverse events (headache and constipation) were observed in 1 case and abnormal change in clinical laboratory findings (increase in eosinophil count) in another case. Out of 42 cases in which safety was evaluated, 41 (98%) cases were assessed as "no problem in safety." However, one case with side effect was assessed as a "Minor problem in safety." From the above, it was confirmed that Ondansetron injection exerted excellent inhibitory effects against nausea and emesis induced by non-platinum anti-cancer drugs, and this drug was a highly safe and useful anti-emetic.
 ...
PMID:[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs]. 138 78

Phase I studies of intravenous (IV) ondansetron in cancer patients receiving emetogenic chemotherapy were designed to assess the degree of antiemetic protection and pattern of adverse events produced by ondansetron at various doses. In a study of 44 patients receiving various forms of chemotherapy (including cisplatin), ondansetron was administered in three IV doses 2 hours apart beginning 30 minutes prior to chemotherapy. Antiemetic efficacy was seen at all dose levels (0.04 mg/kg to 0.35 mg/kg), with 54% of patients experiencing no vomiting and 76% experiencing two or fewer vomiting episodes within the first 24 hours. Overall, ondansetron was well tolerated, and no dose-limiting toxicity was observed. The most common adverse events were mild sedation, mild headache, and transient elevations of transaminases. In a second phase I study, 45 patients receiving cisplatin (median dose 100 mg/m2) were given ondansetron in three IV doses (range, 0.01 mg/kg to 0.48 mg/kg) 4 hours apart. There was no statistically significant difference in antiemetic efficacy among dose levels from 0.06 mg/kg to 0.48 mg/kg; however, there was a trend toward a decrease in the number of patients with failure of antiemetic protection at the higher exposures. Overall, 44% of patients had no emetic episodes, and 81% of patients had two or fewer emetic episodes within the first 24 hours. The number and intensity of adverse events, of which headache was the most common, appeared to increase at the 0.48 mg/kg dose level. A randomized double-blind study that compared three dose levels of ondansetron indicated that three doses of 0.15 mg/kg was superior in efficacy to three doses of 0.015 mg/kg, and not significantly different from three doses of 0.30 mg/kg. Dystonic reactions or akathisia were not noted in any study.
 ...
PMID:Phase I and other dose-ranging studies of ondansetron. 138 46


<< Previous 1 2 3 4 5 6 7 8 9 10