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)

Numerous studies have reported the deleterious impact that the side effects of cytotoxic chemotherapy can exert on the quality of life in patients with cancer. Nausea and vomiting consistently feature as the most distressing aspects of cancer therapy. Uncontrolled emesis can cause patients to abandon treatment and the poor public image of chemotherapy may lead others to refuse treatment altogether. Anticipatory nausea and vomiting can also develop in patients and this may persist for many years after successful completion of treatment. There are several behavioural interventions that are effective in ameliorating or preventing these unpleasant side effects. Consequently, psychological support should be provided as an integral part of good patient management, alongside appropriate antiemetic and anxiolytic drugs. As we can identify the characteristics of those patients more at risk from severe emesis and the development of anticipatory problems, there are good arguments for the most effective drug therapy (rather than the cheapest) being given to them prophylactically, together with relaxation techniques.
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PMID:Behavioural interventions and psychological aspects of care during chemotherapy. 162 7

In order to establish if anticholinergic drugs might influence postoperative nausea and vomiting, 100 ASA I-II adult patients scheduled for minor orthopaedic procedures, varicose vein stripping or inguinal herniorraphy were randomised to receive, in a double-blind fashion, either a premedicant and a reversal dose of 0.003 and 0.0075 mg/kg of glycopyrrolate or 0.006 and 0.015 mg/kg of atropine, respectively. Nitrous oxide, after thiopentone induction was used for anaesthesia with fentanyl and diazepam as supplements and pancuronium for relaxation. In the recovery room, up to 2 h after surgery, 28% of the patients in the glycopyrrolate group and 8% in the atropine group experienced nausea (P = 0.017). Thereafter, the patients complained of nausea at decreased and equal frequencies in both groups. The incidence of vomiting was not statistically significantly different. Droperidol was needed, to control persistent emesis, three times more often in the glycopyrrolate than in the atropine group. It is concluded that substitution of glycopyrrolate for atropine increases the likelihood of postoperative nausea, and continued use of atropine should be considered in patients at risk of postoperative emesis.
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PMID:Do anticholinergic agents affect the occurrence of postanaesthetic nausea? 163 67

In order to decide the administration method of metoclopramide for prevention or control of chemotherapy-induced nausea and vomiting in multidrug chemotherapy, with cisplatin 5-day continuous intravenous infusion (25 mg/m2/day) for patients with advanced lung cancer, a randomised crossover study of intermittent bolus infusion (1 mg/kg, 30 min, every 8 h, day 1-5) and continuous infusion (3 mg/kg/24 h, 120 h) of metoclopramide was performed. Both regimens included methylprednisolone and diphenhydramine given concurrently. The acute and delayed antiemetic effects were examined. 21 cases could be evaluated. There were 6 and 10 cases (P = 0.048), respectively, of no nausea and no vomiting; 14 and 18 cases (P = 0.048), respectively, of no vomiting; and vomiting episodes were seen 27 and 9 times, respectively (P = 0.042). Thus, metoclopramide continuous infusion was significantly superior in antiemetic effect compared to bolus infusion. Neither method had any serious side-effects and both were safe.
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PMID:Comparison of continuous and intermittent bolus infusions of metoclopramide during 5-day continuous intravenous infusion with cisplatin. 164 44

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.
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PMID:Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting. 165 11

Fundamental approaches in selection of new agents for evaluation in prevention of space/motion sickness (SMS) are reviewed. The discussion centers on drugs under investigation at the Johnson Space Center. Methodology that employs the rotating chair for measuring SMS symptomatology and susceptibility is described. The most obvious approach to the development of new agents relies on selection of agents from drug classes that possess pharmacologic properties of established anti-motion sickness agents. A second approach selects drugs that are used to prevent emesis caused by means other than exposure to motion. The third approach relies on basic research that characterizes individual differences in susceptibility. The hypothesis is: detection of individual differences leads to identification of specific drugs, which target physiologic systems that show individual differences. These physiologic systems are targets for therapy and may play a role in the etiology of SMS. Two drugs that reduce susceptibility to SMS include dexamethasone and d(CH2)5Tyr(Me)AVP, a vasopressin (AVP)V1 antagonist. The latter peptide has demonstrated complete blockade of emesis and other significant symptoms in squirrel monkeys. These studies were predicated on observations that subjects who were more resistant to SMS had higher plasma AVP after severe nausea than subjects with lower resistances. Investigations are underway to test a 0.5-mg intravenous dose in humans. Kappa opioid agonists inhibit AVP release and offer new therapeutic possibilities and advantages over AVP peptides. This review details the experimental data collected on AVP and adrenocorticotropin. The literature supports interrelated roles for AVP and opioid peptides in SMS. Experimental testing of kappa agonists is warranted because specific opioid agonists act at neuroanatomical sites causing nausea and vomiting. It is argued opioid receptors in the chemoreceptor trigger zone and vomiting center stimulate and inhibit the emetic response, respectively. The evidence suggests kappa and/or mu receptors at VC are involved in inhibition of emesis, whereas delta opioid receptors at CTZ are involved in stimulation of emesis.
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PMID:New pharmacologic approaches to the prevention of space/motion sickness. 166 31

Despite excellent control of acute-stage emesis, some patients are still bothered by delayed emesis occurring more than 24 hours after cisplatin administration. We report 19 patients with 61 courses of cisplatin-based chemotherapy. They all received high-dose metoclopramide, dexamethasone and lorazepam on the day of cisplatin treatment. After 24 hours, they were treated with intravenous dexamethasone 8 mg once and metoclopramide 50 mg twice on day 2, and oral metoclopramide 10 mg qid on days 3-5. Delayed vomiting and nausea were noted in 27.9% and 39.4% respectively, as compared with 69.8% of delayed emesis and 79.4% of delayed nausea in 63 courses of 15 patients without receiving any antiemetics on days 2-5. The statistics showed significant difference (both P less than 0.001). Side effects were mild and acceptable. Therefore, this regimen is highly effective in preventing delayed vomiting and nausea.
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PMID:[Control of cisplatin-induced delayed emesis]. 166 84

In recent years a new class of agents, the serotonin type 3 receptor antagonists, has been identified. This article reviews the preclinical, pharmacological and clinical data of ondansetron, granisetron and tropisetron, the first representatives of this group. Preclinical work showed that the drugs interfere with a variety of physiological processes, and hold promise for clinical utility in a wide range of areas. To date, these agents have proven, both in early clinical and comparative studies, to be potent antiemetic agents in patients receiving cisplatin and non-cisplatin chemotherapy as well as radiotherapy. In comparative studies the antiemetic efficacy mostly has been superior to conventional antiemetic drugs with regard to the acute chemotherapy-related symptoms; whereas their role in delayed emesis needs further investigation. This also applies for their role as an antiemetic in other types of nausea and vomiting (post-operative). Toxic effects have been modest, no extrapyramidal reactions have been reported. Potential clinical use in psychiatric disorders has been suggested, and the results of clinical trials are awaited.
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PMID:5-HT3 receptor antagonists, a new approach in emesis: a review of ondansetron, granisetron and tropisetron. 166 23

We have monitored the expression of c-fos protein in the medulla oblongata of the ferret, using immunocytochemistry, to identify the brainstem pathways involved in the mediation of nausea and vomiting caused by the antineoplastic drug cisplatin. Cisplatin administration resulted in c-fos-like immunoreactivity (FLI) in the area postrema, the nucleus of the solitary tract, and in scattered cells within the ependymal lining of the fourth ventricle. Unilateral cervical vagotomy greatly reduced FLI in the ipsilateral nucleus of the solitary tract but did not significantly affect reactivity in the contralateral solitary tract nucleus or in the area postrema. Pretreatment of the animals with the 5-HT3 antagonist granisetron (BRL 43694) abolished the retching and vomiting caused by cisplatin and markedly reduced the cisplatin-evoked FLI in the nucleus of the solitary tract; treatment with this drug had no significant effect on cisplatin-evoked FLI in the area postrema. The results suggest that cisplatin induces c-fos gene expression in the nucleus of the solitary tract by an action involving vagal afferent pathways and also by a vagally independent, direct action on the area postrema. The anti-emetic 5-HT3 antagonist drug granisetron mimicked the effect of vagotomy on c-fos protein induction suggesting that it may act via 5-HT3 receptors known to be associated with vagal afferent terminals. The FLI seen in the area postrema was neither vagally dependent nor was it abolished by granisectron.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin-evoked induction of c-fos protein in the brainstem of the ferret: the effect of cervical vagotomy and the anti-emetic 5-HT3 receptor antagonist granisetron (BRL 43694). 166 10

Both radiotherapy and chemotherapy for cancer are capable of causing severe nausea and vomiting, which formerly often interfered with the patient's compliance to treatment. The basic pathway and pharmacological mechanisms involved in this are still poorly understood. The recent discovery, however, that 5-HT3 receptor antagonists can prevent or greatly reduce chemotherapy-induced emesis led to a re-evaluation of the sequence of events occurring in the protective emetic reflex, which are reviewed in this paper. The vomiting centre co-ordinates the incoming and outgoing information, and is thought to be represented by complex interactions between different adjacent areas in the brainstem. Whether the main role in the emetic reflex arch is accomplished by either the central part (chemoreceptor trigger zone) or the peripheral part (gastro-intestinal tract) needs further confirmation A more important role, however, of the vagal nerve and the gastro-intestinal tract is generally accepted. The neurotransmitter serotonin (5-HT) appears to play a major role in chemotherapy-induced emesis via the 5-HT receptor. These indications could form the basis for further investigations into the involvement of other neurotransmitters, and the character of their interactions.
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PMID:Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear. 167

A total of 24 patients who were receiving combination chemotherapy (POMB) including cisplatin at a dose of 100-120 mg/m2 were treated with the 5HT3 antagonist GR38032F (GR) as an anti-emetic prophylaxis. GR was given as a 15-min loading infusion followed by a 24-h infusion at three escalating dose levels of 1, 2 and 4 mg/h. In the first 24 h after commencing treatment, six patients had complete control of nausea and vomiting (CR), two had 1-2 emetic episodes (MR) and five had 3-5 emetic episodes (mR). The major response rate (CR + MR) was thus 35%. Eight responding patients (CR or MR) went on to receive oral GR at 8 or 12 mg t.i.d. for 5 days. In this group there was one CR, one MR, two mRs and four failures (F). There was no evidence of an improved therapeutic effect with increasing dose in either the infusion or the oral section of the study, although numbers were limited in the latter part of the trial. Toxicity was mild, with low-grade headache affecting 25% of patients being the most frequent side effect. Pharmacokinetic data was obtained in six patients at each dose level. There was a progressive rise in clearance with increasing dose, indicating that the kinetics are non-linear. However, there was no evidence of an association between high plasma levels and therapeutic efficacy. GR38032F is well tolerated and has promising single-agent activity in preventing vomiting induced by high-dose cisplatin.
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PMID:A phase I/II study of the 5-HT3 antagonist GR38032F in the anti-emetic prophylaxis of patients receiving high-dose cisplatin chemotherapy. 168 16


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