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)

Male and female cynomolgous monkeys were administered 0, 2, 6 or 18 mg/kg 8-methoxypsoralen (8-MOP) 3 times a week orally for 26 consecutive weeks. Dose-dependent emesis was the most sensitive indicator of 8-MOP toxicity. The lowest dose to elicit emesis was 3 x 6 mg/kg/week of 8-MOP. Among the histological findings proliferation of Kupffer cells was the only recurring observation. However, these finding as well as some hematological and serum electrolyte changes lacked a dose-response relationship. In the highest dosage group one female monkey was found in moribund condition on the 39th day of the study and was killed. Histopathological evidence indicated beginning shock as the cause of the rapidly deteriorating health of the monkey. Similar to effects in man and rats, 8-MOP displayed nonlinear pharmacokinetics in the cynomolgous monkey, saturation occurring between 3 x 2 and 3 x 6 mg/kg/week. Increased clearance of 8-MOP in the lowest dosage group after 26 test weeks was attributed to a combination of enzyme induction and saturable first pass effect. Since the plasma profile of 8-MOP at the lowest dose (3 x 2 mg/kg/week) in cynomolgous monkeys closely resembles that in humans after therapeutic doses (0.4-0.6 mg/kg) and because of other similarities (vomiting as earliest sign of toxicity, saturable first pass effect), it is reasonable to assume that chronic toxicity of 8-MOP as defined in this study is quite predictive for man.
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PMID:Toxicity of 8-methoxypsoralen in cynomolgous monkeys (Macaca fascicularis). 271 6

In animal models of vomiting, mu-opioid (MOP, OP(3)) receptors mediate both emesis and anti-emesis. mu-receptors within the blood-brain barrier, mediating anti-emesis, are more rapidly accessible to lipid-soluble mu-opioid receptor agonists such as fentanyl than to morphine, and fentanyl has broad-spectrum anti-emetic effects in a number of species. Whether a similar situation exists in humans is not known. A search was performed for clinical studies comparing the emetic side effects of opioids administered peri-operatively in an attempt to identify differences between morphine and more lipid-soluble mu-receptor-selective agonists such as fentanyl. Overall, the evidence appears to suggest that fentanyl and other phenylpiperidines are associated with less nausea and vomiting than morphine, but not all studies support this, and fentanyl-like drugs are associated with nausea and vomiting per se. Good evidence, however, exists to show that fentanyl and alfentanil do not cause more nausea and vomiting than the ultra fast-acting remifentanil. Because remifentanil is cleared rapidly post-operatively, such trials suggest that the emetic side effects of fentanyl and alfentanil are minimal. The clinical evidence, although limited, is at least consistent with the possibility that central mu-opioid receptors may mediate anti-emesis in humans. It is possible that the role of mu-opioid agonists in anti-emesis may become clearer in the future as a result of the use of peripheral mu-opioid receptor antagonists.
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PMID:The potential for mu-opioid receptor agonists to be anti-emetic in humans: a review of clinical data. 2007 49

The aim of the present study was to investigate the analgesic effect and safety of the application of different doses of nalbuphine in patient-controlled intravenous analgesia (PCIA) for patients undergoing subtotal gastrectomy. A total of 120 patients, who underwent subtotal gastrectomy at our hospital between May, 2015 and January, 2017 under combined spinal epidural combined anesthesia, were selected. The patients received PCIA after surgery. The patients were randomly divided into four groups, including the morphine (MOP group), nalbuphine 60 mg (N60 group), nalbuphine 80 mg (N80 group) and nalbuphine 100 mg (N100 group). The first dose of PCIA treatment was 2 ml, the background dose was 2 ml/h, PCIA dose was 0.5 ml, and the lockout time was 15 min. Postoperative vital signs and adverse reactions (bleeding, fullness and aching of upper abdomen and vomiting) were recorded. The visual analogue scale (VAS) and Ramsay sedation score of patients were evaluated. The number of PCIA and analgesia-related complications during analgesia were recorded. No significant differences in general data were found among the four groups (P>0.05). The VAS score of the three nalbuphine groups was lower than that of the MOP group, but the differences were not significant. All postoperative Ramsay sedation scores of the four groups showed appropriate sedation, but no significant differences were found between the groups. Compared with the MOP group, the use of postoperative PCIA was significantly delayed and the number of PCIA was significantly smaller in the three nalbuphine groups (P<0.05). The results show that the analgesic effect and safety of the use of PCIA for patients undergoing subtotal gastrectomy were satisfactory.
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PMID:The application of nalbuphine in patient-controlled intravenous analgesia for patients undergoing subtotal gastrectomy. 2943 83