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)

Cis-platinum causes profound gastrointestinal symptoms in patients and these may persist for many days after drug administration. Gut mucosal toxicity may be a factor in the pathogenesis of such prolonged nausea, vomiting and anorexia. The effects of cis-platinum on mouse ileal mucosal architecture, villus epithelial cell influx and disaccharidase activity are described in comparison with dhe effects of two platinum analogues, CBDCA and CHIP. In addition the effect of dexamethasone, a useful drug in the palliation of cis-platinum-induced emesis, in combination with cis-platinum is described. Cis-platinum, CBDCA and CHIP cause profound reduction in crypt cell production rate (CCPR) and thus villus epithelial cell influx within hours of administration leading to villus stunting and diminished function. CBDCA showed the least profound effect with early rebound in CCPR by day 3. Cis-platinum and CHIP were roughly equitoxic to ileal crypts with rebound in CCPR being delayed until day 7. Similarly, CBDCA caused least reduction in disaccharidase activity with cis-platinum and CHIP being equitoxic. The addition of dexamethasone had no protective effect on the effects of cis-platinum on murine ileal mucosa and mice given the combination chronically had no weight gain over 18 weeks, their weight paralleling those receiving cis-platinum alone. The platinate compounds have differing degrees of intestinal mucosal toxicity but no direct inference can be drawn in respect to the clinical situation where CBDCA causes less gastrointestinal symptomatology than CHIP but where both cause less than cis-platinum. Dexamethasone does not act by mucosal protection to provide its useful effects in prolonged cis-platinum-induced gastrointestinal symptoms.
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PMID:Small intestinal mucosal toxicity of cis-platinum--comparison of toxicity with platinum analogues and dexamethasone. 351 92

A double-blind, randomized, crossover study was conducted to compare the efficacy and safety of high-dose dexamethasone and high-dose metoclopramide in the treatment of chemotherapy-induced nausea and vomiting. All entered patients had no prior chemotherapy and all received inpatient emetogenic chemotherapy mainly without cisplatin. Of the 40 evaluable patients, 23 (58%) had no vomiting with dexamethasone compared with only 11 (28%) receiving metoclopramide (P less than 0.025). Dexamethasone was found to have less adverse effect than metoclopramide on patient's appetite and activity (P less than 0.025 and P less than 0.01, respectively). Twenty-one patients (53%) developed mild to severe somnolence with metoclopramide compared to only seven (18%) who experienced this adverse effect with dexamethasone (P less than 0.01). Six patients (15%) developed extrapyramidal manifestations with metoclopramide, but none with dexamethasone. Furthermore, during dexamethasone therapy, patients developed less diaphoresis, insomnia, headache and dizziness. Upon questioning patients about their preference to future use of the antiemetic drug therapy, 28 patients (70%) preferred dexamethasone, two (5%) preferred metoclopramide and 10 (25%) found no difference. We conclude that high-dose dexamethasone has a greater antiemetic activity and is more safe than high-dose metoclopramide in patients receiving emetogenic chemotherapy mainly without cisplatin.
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PMID:Antiemetic efficacy of high-dose dexamethasone: randomized, double-blind, crossover study with high-dose metoclopramide in patients receiving cancer chemotherapy. 351 33

High-dose intravenous (IV) metoclopramide has shown efficacy with few side effects for the treatment of nausea and vomiting on the day of cisplatin administration. From November 1984 to January 1986, two randomized trials in an antiemetic study were conducted. In trial I, the antiemetic effect of a short course of high-dose dexamethasone was compared with that of high-dose metoclopramide in 29 patients with lung cancer receiving chemotherapy containing cisplatin (80 mg/m2 IV) in a randomized controlled trial. Dexamethasone was given IV at a dose of 16 mg 1/2 hr before and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr before and 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emetic control (0-2 episodes of vomiting) during the 24 hr after cisplatin administration was achieved in 55% (6/11) and 67% (12/18) of the patients receiving dexamethasone and metoclopramide, respectively, without serious toxicity. The duration of nausea or anorexia was similar for the two treatment groups. In trial II, the combination of metoclopramide and dexamethasone was compared with metoclopramide alone to assess the additive antiemetic effect of the two drugs in 23 patients with lung cancer receiving cisplatin at a dose of 120 mg/m2 IV in a randomized cross-over study. A major antiemetic response was observed in 27% (3/11) and 92% (11/12) of the patients receiving metoclopramide alone and metoclopramide plus dexamethasone, respectively (p less than 0.005). The duration of nausea and anorexia was similar for the two treatment groups. Patients tended to prefer the combination of metoclopramide and dexamethasone; however, the difference was not statistically significant (p = 0.14) in the small number of patients entered in this study. Despite excellent control of acute chemotherapy-induced emesis, 45% of 52 patients experienced delayed nausea and vomiting more than 24 hr after cisplatin administration even among those who had had an excellent short-term response to the antiemetic agents.
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PMID:Antiemetic efficacy of high-dose intravenous metoclopramide and dexamethasone in patients receiving cisplatin-based chemotherapy: a randomized controlled trial. 353 48

This prospective, randomized, nonblind study comparing the antiemetic effectiveness of high-dose IV metoclopramide and high-dose IV dexamethasone was performed in 78 advanced cancer patients. Chemotherapeutic treatment consisted in cisplatin at a high-dose (120 mg/m2) (HD-CDDP) and at a low-dose (LD-CDDP), either alone (60 mg/m2) or in combination with other chemotherapeutic agents (50 mg/m2). The evaluation of the effectiveness of antiemetic therapy was based on three parameters: prevention of vomiting ("major protection"), number of emetic episodes, and subjective preference. Out of 78 study patients, 67 were evaluable. Overall, metoclopramide proved to be statistically superior to dexamethasone in preventing vomiting (P less than 0.005), in reducing the median/mean number of emetic episodes (P less than 0.001/0.001), and in subjective preference (P less than 0.01). The results divided between HD-CDDP and LD-CDDP groups were also in favor of metoclopramide for reduction of the median/mean number of emetic episodes (P less than 0.001/0.001 for the HD-CDDP group and P less than 0.001/0.005 for the LD-CDDP group) and in subjective preference (P less than 0.001 and P less than 0.001 for the HD- and LD-CDDP groups, respectively). No statistical differences were noted when LD-CDDP was used in monochemotherapy, whereas when LD-CDDP was used in combination chemotherapy, statistical differences in favor of metoclopramide were noted again for the median/mean number of emetic episodes (P less than 0.01/0.05) and for subjective preference (P less than 0.01), even though the effectiveness of both antiemetic agents was greatly reduced. The evaluation of previously untreated patients reflected the overall results: for the HD-CDDP group all three parameters demonstrated statistical significance in favor of metoclopramide; for the LD-CDDP group, of all three parameters, prevention of vomiting (major protection) was the only one for which there was no significant difference. Mild sedation was the only side effect of metoclopramide. No extrapyramidal reactions were noted during this trial, but concomitant orphenadrine treatment was given. Dexamethasone was always well tolerated. In conclusion, high-dose IV metoclopramide demonstrated its superiority over high-dose IV dexamethasone in all subsets of our population except the LD-CDDP monochemotherapy group, in which the two antiemetics were found to be equivalent in effect.
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PMID:Randomized crossover antiemetic study in cisplatin-treated patients. Comparison between high-dose i.v. metoclopramide and high-dose i.v. dexamethasone. 369 80

Clinical findings for 5 new cases of colonic perforation in corticosteroid-treated dogs were presented and 8 other cases from the literature were reviewed. Colonic perforation was a fatal complication in all 13 dogs, 12 of which had had recent major surgery. Ten dogs were neurosurgical patients, 1 dog received medical therapy for head trauma and nonambulatory paresis, and 2 dogs were operated on for non-neurologic conditions. Dexamethasone was the most frequently used corticosteroid, and 12 dogs received a mean cumulative dose of 6.4 mg/kg over an average period of 5.1 days. Depression, anorexia, and emesis, the most frequent signs attending colonic perforation, became evident 3 to 8 days after surgery. Signs preceded death by an average of 22.3 hours. Correct antemortem diagnosis (5 dogs) and surgical intervention (3 dogs) had no effect on eventual outcome (mortality = 100%). Colonic perforation most frequently developed in the proximal descending portion and always involved the antimesenteric border. Gross fecal contamination of the peritoneal cavity and acute generalized peritonitis were evident in all but one dog. Adhesions were observed at the lesion site in 6 dogs, but prevented gross soilage in only one dog.
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PMID:Colonic perforation in corticosteroid-treated dogs. 370 Feb 9

Male pseudohermaphroditism in a 6 month old boy, due to congenital 3 beta-hydroxysteroid dehydrogenase deficiency, associated with atrial septal defect, is reported. At 2 weeks he required therapy for severe dehydration and projectile vomiting. The parents were first cousins and one female sibling had died suddenly at 2 months. The patient presented with melanoderma, perineal hypospadias with testicles in a bifid scrotum and atrial septal defect (ostium secundum). Complete cytogenetic studies showed a 46,XY karyotype. Serum sodium ranged from 129 to 140 mEq/l and serum potassium from 5.1 to 4.6 mEq/l. Basal plasma hormonal studies showed normal androstenedione (delta 4A), decreased cortisol (F), slightly elevated ACTH, 17-hydroxy-progesterone (17-OH-P) and testosterone (T), and highly increased dehydroepiandrosterone-sulphate (DHEA-S) levels. ACTH stimulation increased and DXM suppression decreased the plasma levels of DHEA-S, 17-OH-P and T but not that of F; hCG stimulation during cortisone therapy did not change the levels of DHEA-S and T. Corticosteroid therapy normalized electrolyte levels and reduced melanoderma and hormonal hypersecretion. Moderately elevated plasma levels of 17-OH-P and T suggest a partial testicular 3 beta-HSD deficiency. The multifactorial inheritance and the relatively high prevalence of atrial septal defect vs the rarity of adrenal enzymatic defect suggest a causal association even if a common genetic factor cannot be excluded.
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PMID:Male pseudohermaphroditism due to 3 beta-hydroxysteroid dehydrogenase-isomerase deficiency associated with atrial septal defect. 386 11

Evaluation of the activity of anti-emetic drugs in randomized controlled trials has, in most cases, demonstrated the superiority of treatment over placebo administration for the control of chemotherapy-induced emesis (see Table 15). The degree of control of emesis relates both to the intensity of the emetogenic stimulus and to the effectiveness of the anti-emetic agent employed. Prochlorperazine is a relatively weak anti-emetic. The drug exhibits modest activity in the treatment of emesis produced by mild emetogenic stimuli, but is relatively ineffective in the treatment of patients on moderate to severely emetogenic drugs. Domperidone has demonstrated activity against moderately emetogenic stimuli but has not been evaluated in cisplatin-treated patients. The cannabinoids have proved efficacious in the treatment of emesis induced by more severe emetogenic stimuli. THC therapy, however, has been limited in some studies by toxicity. High-dose metoclopramide has demonstrated efficacy in small series of patients in the treatment of cisplatin-induced vomiting. Dexamethasone activity as a single agent is in doubt but the drug may improve the efficacy of metoclopramide when used in combination. For the future, the use of combinations of anti-emetics with differing sites of action and non-overlapping toxicities, may lead to further improvement in efficacy. Combinations of centrally-acting drugs such as the cannabinoids plus dopamine antagonists such as metoclopramide or domperidone, are worth evaluating. The control of anticipatory nausea and vomiting is another major area of interest which has, as yet, not been studied in any depth. A single comparative trial has been reported in the literature (50) and in this study, behavioural therapy rather than drug therapy was evaluated. There may be a place for the evaluation of behavioural therapy in combination with drugs exhibiting anxiolytic properties such as the benzodiazepines and the cannabinoids. Finally, new anti-emetic drugs with an improved therapeutic index will be welcomed by the patient.
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PMID:Advances in anti-emetic therapy. 609 68

To assess the value of high-dose dexamethasone therapy in preventing the gastrointestinal (GI) side effects of chemotherapy, a randomized double-blind study was conducted in women receiving outpatient therapy for breast cancer. Single-dose dexamethasone sodium phosphate (10 mg) or placebo was administered intravenously in 57 trials in 22 women immediately before chemotherapy. Questionnaires (administered before therapy and 24 hours later) were compared for evidence of nausea, vomiting, and anorexia produced by chemotherapy. No GI intolerance to chemotherapy was noted in 24 (83%) of the 29 dexamethasone trials v 16 (57%) of the 28 placebo trials. Dexamethasone trials produced the following results: no side effects in 50% (14/29), insomnia the night after chemotherapy in 21% (6/29), an increase in energy levels in 24% (7/29), and an improvement in mood in 14% (4/29). High-dose dexamethasone therapy has useful application in alleviating the emetic effects of cancer chemotherapy.
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PMID:Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. 634 9

In a pilot study a combination of metoclopramide and dexamethasone was administered to 29 patients receiving emetogenic chemotherapy. Metoclopramide was given intravenously (IV) at a dose of 0.5 mg/kg one-half hour before the start of chemotherapy, and then given at the same dose orally two, five, and eight hours after chemotherapy. Dexamethasone was given at a dose of 10 mg IV immediately following the first dose of metoclopramide, then given at a dose of 8 mg orally six, 12, and 18 hours after chemotherapy. The chemotherapy regimens most commonly used were standard FAC, FAM, and BACOD regimens. Twenty-six of 29 patients received outpatient treatment. Complete protection against both nausea and vomiting was seen in 69% (20/29) patients; six others (21%) experienced mild nausea but no vomiting, resulting in 90% (26/29) of the patients having total emetic protection with combination metoclopramide and dexamethasone. Eighty-eight percent (15/17) of the patients with no prior chemotherapy had no nausea or vomiting, one (6%) had only mild nausea, and the remaining patient (6%) had one emesis. Forty-two percent (5/12) of the patients with prior chemotherapy had complete antinausea and emetic protection, five (42%) had nausea without vomiting, and the remaining two patients experienced one or two emesis. Side effects were minimal when present and included mild drowsiness (five patients), akathisia (three patients), diarrhea (one patient), and hot flashes (one patient). Combination metoclopramide and dexamethasone therapy can effectively prevent emesis in 94% of patients receiving potentially emetogenic chemotherapy and can prevent nausea and emesis in 88% of untreated patients. Studies defining the optimal dose and scheduling needed to maintain such antinausea and antiemetic protection are necessary.
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PMID:Combination metoclopramide and dexamethasone: an effective antiemetic regimen in outpatients receiving non-cisplatin chemotherapy. 647 Jul 55

Nausea and vomiting remain common and debilitating side effects of therapy with many anticancer drugs. Recent reports have shown that both metoclopramide and dexamethasone are effective drugs for the treatment of severe nausea and vomiting caused by cis-platinum. A double-blind crossover study comparing the antiemetic properties of high-dose oral and intravenous regimens of metoclopramide and dexamethasone in outpatients was carried out. Standardized patient questionnaires and interviews were used to evaluate response. Dexamethasone and metoclopramide protected against more than five episodes of emesis in 48% and 40% of patients, respectively. Nausea persisted for less than six hours in 45% of patients on dexamethasone and in 37% on metoclopramide. The antiemetic efficacy of both regimens was retained through repeated courses of chemotherapy. Side effects were minimal with dexamethasone; however, 33% of patients experienced unacceptable extrapyramidal side effects to metoclopramide. Patient preference was significantly in favor of dexamethasone: 70% of patients chose to continue dexamethasone compared to 22% who preferred metoclopramide and 8% who chose other antiemetics. Dexamethasone was the preferred antiemetic in this patient population due to minimal side effects.
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PMID:Double-blind crossover study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide. 653 63


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