dezocine
218599090
Dezocine regulates the malignant potential and aerobic glycolysis of liver cancer targeting Akt1/GSK 3b pathway.
Background Due to the "ceiling effect" of respiratory depression and the non addictiveness, the consumption of dezocine is increasing quickly in the cancer surgery perioperative period for security and comfort reasons in China. Former studies find dezocine inhibits the norepinephrine transporters (NET) and serotonin transporters (SERT) and sigma 1opioid receptors. Given the complexity of the molecular mechanism, the effect of dezocine on tumor cells need to be studied. In this study, we investigated the effect of dezocine on HepG2 and Hep 3B liver cancer cell lines growth and glycolysis, and the molecular mechanisms behind. Methods HepG2 and Hep 3B cells viability and migration were measured by CCK8, Wound healing and transwell assay, Extracellular acidification rate (ECAR) was used to index the aerobic glycolysis of liver cancer cells and western blot analysis showed protein expression levels in the cells. SC79, an agonist of Akt, and the siRNA silence of Akt1 aimed to regulate Akt1 activity and expression in the reverse experiments. Results Dezocine played opposite roles in HepG2 and Hep 3B cells viability and migration in a concentration dependent manner (P<0.01) Dezocine has diverse effects on aerobic glycolysis and adjusts the serine/threonine kinase 1 (Akt1) glycogen synthase kinase 3b (GSK 3b) pathway. The effects of SC79 and the siRNA silence of Akt1 could reverse the effects of dezocine on HepG2 and Hep 3B cells. Conclusions As an analgesic drug widely used in clinical practice, dezocine play reversed roles on HepG2 and Hep 3B cells viability and migration targeting Akt1/GSK 3b pathway then the glycolysis in a concentration dependent manner.
Annals of translational medicine
Zi-Wen Zhong Wen-Chang Zhou Xingyun Sun Qichao Wu Wan-kun Chen Chang-hong Miao
219959030
Dezocine prevents sufentanil induced cough during general anesthesia induction: a meta analysis of randomised controlled trials
Background Sufentanil is one of the opioids currently used to induce general anesthesia, and cough is one of the most common complications. Many drugs have been used to prevent sufentanil induced cough (SIC) and dezocine is one of them. Dezocine is an analgesic, acting as partial antagonist of k receptors and agonist of m receptors. The purpose of our meta analysis is to evaluate the efficacy of dezocine on SIC. Methods We searched multiple databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and China National Knowledge Infrastructure databases (CNKI) to identify studies that met the inclusion criteria. This meta analysis focused on the incidence and severity of SIC after dezocine intervention, as well as adverse effects. This meta analysis was registered on PROSPERO with reference number ID: CRD 42020144943. Results Five randomised controlled trials (RCTs) were identified, including 890 patients. Each study was a comparison of dezocine with an equal volume of 0.9% saline. When the injection dose of dezocine was 0.1 mg/kg, the incidence (pooled risk ratio (RR) 0.03, [95% CI: 0.02 to 0.07] P 0.00001, I 2 0% and severity (mild: RR 0.07, [95% CI: 0.03 to 0.18] P 0.00001, I 2 0% moderate: RR 0.05, [95% CI: 0.02 to 0.16] P 0.00001, I 2 0% severe: RR 0.04, [95% CI: 0.01 to 0.16] P 0.00001, I 2 0% of SIC were significantly decreased. There were no statistically significant differences in vital signs between the two groups based on the results of the pooled analysis. Conclusion This meta analysis showed that dezocine significantly reduced the incidence and severity of SIC in the induction of general anesthesia, but had no significant effect on vital signs. More high quality RCTs are needed to complement existing conclusions.
BMC Anesthesiology
Zhencheng Xiong Ping Yi Jipeng Song Mingsheng Tan
220936881
Effects of Dexmedetomidine on the Pharmacokinetics of Dezocine, Midazolam and Its Metabolite 1 Hydroxymidazolam in Beagles by UPLC MS/MS
Objective We developed and validated a sensitive and reliable UPLC MS/MS method for simultaneous determination of dezocine (DEZ) midazolam (MDZ) and its metabolite 1 hydroxymidazolam (1 OH MDZ) in beagle plasma and investigated the effect of dexmedetomidine (DEX) on the pharmacokinetics of DEZ, MDZ and 1 OH MDZ in beagles. Materials and Methods Diazepam was used as the internal standard (IS) the three analytes and IS were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column using acetonitrile 0.1% formic acid as mobile phase in gradient mode. In positive ion mode, the three analytes and IS were monitored by multiple reaction monitoring (MRM) Six beagles were designed as a double cycle self control experiment with 0.15 mg/kg in the first cycle (Group A) After a 1 week washout period, the same six beagles were slowly injected intravenously with 2 ug/kg DEX in the second cycle (Group B) with continuous injection for 7 days. On the seventh day, 0.5 hr after intravenous injection of 2 ug/kg DEX, the six beagles were intramuscularly given with DEZ 0.33 mg/kg and MDZ 0.15 mg/kg. Results Under the conditions of this experiment, this method exhibited a good linearity for each analyte. The accuracy and precision were all within the acceptable limits in the bioanalytical method, and the results of recovery, matrix effect and stability have also met the requirements. Conclusion The developed UPLC MS/MS method for simultaneous determination of DEZ, MDZ and 1 OH MDZ in beagles plasma was accurate, reproducible, specific, and suitable. DEX could inhibit the metabolism of DEZ and MDZ and increase the exposure of DEZ and MDZ in beagles. Therefore, the change of therapeutic effect and the occurrence of adverse reactions caused by drug drug interaction should be paid attention to when the drugs were used in combination.
Drug design, development and therapy
Wei Zhou Shuang-Long Li Ti Zhao Le Li Wenguo Xing Xiang-jun Qiu Wei Zhang
219926551
Is dezocine effective and safe in preventing opioids induced cough during general anaesthesia induction? A protocol for systematic review and meta analysis
Introduction Cough is often observed when administrating a bolus of opioids. Opioid induced cough (OIC) is mostly transient, benign and self limiting, but could be associated with adverse effects. Numerous pharmacological and non pharmacological interventions have been used to manage OIC with controversial efficacy and safety. Recent studies suggested that, pretreatment of intravenous dezocine (DZC) could completely suppress OIC during anaesthesia induction. To address this knowledge lack, we will perform a systemic review and meta analysis to evaluate the efficacy of DZC on OIC and possible complications. We provide here a protocol that will outline the methods and analyses planned for the systematic review. Methods PubMed, Embase, Cochrane Library, Web of Science as well as Chinese BioMedical Literature Retrieval System (SinoMed) China National Knowledge Infrastructure, Wanfang Data and VIP Data will be searched from 1978 to 31 December 2019 to identify all randomised controlled trials comparing DZC with placebo on the incidence and severity of OIC. Primary outcomes of interest include the incidence and severity of OIC. Secondary outcomes of interest include possible complications or adverse effects of DZC. Two authors will independently extract relevant variables and outcome data. For continuous variables, treatment effects will be calculated as weighted mean difference and 95% CI. For dichotomous data, treatment effects will be calculated as OR and 95% CI. Each outcome will be tested for heterogeneity, and randomised effects or fixed effects model will be used in the presence or absence of significant heterogeneity. Sensitivity analyses will be done by examining the influence of statistical model and individual trial(s) on estimated treatment effects. Publication bias will be explored through visual inspection of funnel plots of the outcomes. Statistical significance will be defined as p<0.05. Ethics and dissemination This study is a protocol of meta analysis of previously published literatures, ethical approval was not necessary according to the Ethical Committee of Fuwai Hospital. The study will be submitted to a peer reviewed journal and disseminated via research presentations. PROSPERO registration number CRD42019141255.
BMJ Open
Li-Xian He Ken Shao Jie Ma Yuan-Yuan Zhao Yun-Tai Yao
218910152
Postoperative analgesia using dezocine alleviates depressive symptoms after colorectal cancer surgery: A randomized, controlled, double blind trial
Background Postoperative depression is one of the most common mental disorders in patients undergoing cancer surgery and it often delays postoperative recovery. We investigated whether dezocine, an analgesic with inhibitory effect on the serotonin and norepinephrine reuptake, could relieve postoperative depressive symptoms in patients undergoing colorectal cancer surgery. Methods This randomized, controlled, single center, double blind trial was performed in the Second Affiliated Hospital of the Army Medical University. A total of 120 patients were randomly assigned to receive either sufentanil (1.3 mg/kg) with dezocine (1 mg/kg) (dezocine group; n 60) or only sufentanil (2.3 mg/kg) (control group; n 60) for patient controlled intravenous analgesia after colorectal cancer surgery. The primary outcome was the Beck Depression Inventory score at 2 days after surgery. The secondary outcomes included the Beck Anxiety Inventory, sleep quality, and quality of recovery scores. Results Compared with those in the control group, patients in the dezocine group had lower depression scores (7.3+ 3.4 vs. 9.9+ 3.5, mean difference 2.6, 95% CI: 1.4 3.9; P<0.001) at 2 days after surgery and better night sleep quality at the day of surgery (P 0.010) and at 1 day after the surgery (P<0.001) No significant difference was found in other outcomes between the two groups. Conclusions Intravenous analgesia using dezocine can relieve postoperative depression symptoms and improve sleep quality in patients undergoing colorectal cancer surgery.
PloS one
Pengg Zhao Zhuoxi Wu Chunrui Li Guiying Yang Jinping Ding Kai Wang Mingming Wang Lijuan Feng Guang-you Duan Hong Li
220333094
Sufentanil and remifentanil combined with dezocine anesthesia for radical resection of liver cancer and its effect on liver and kidney function
Objective: To study the effect of sufentanil and remifentanil combined with dezocine on radical resection of liver cancer and its effect on liver and kidney function. Methods: Altogether 137 patients who underwent radical resection of liver cancer in Hanchuan Traditional Chinese Medicine Hospital of Hubei from February 2016 to June 2018 were collected; 72 of whom were treated with sufentanil combined with dezocine as the observation group (OG) and 65 of whom were treated with remifentanil combined with dezocine as the control group (CG) The stress state, VAS score, liver and kidney function index and postoperative adverse reactions of the two groups were observed 15 minutes before anesthesia (T0) at skin incision (T1) at surgery completion (T2) and 24 hours (T3) after operation. Results: The stress state of the OG at T1, T2 and T3 was greatly lower than that of the CG, and the VAS score of the OG was lower than that of the CG. There was no remarkable difference in adverse reactions between the two groups, and no difference in liver function indicators ALT, AST and renal function indicators Cr and BUN. Conclusion: Sufentanil combined with dezocine can provide more stable hemodynamics, reduce stress responses and reduce postoperative pain, but there is no difference in the liver and kidney function compared with remifentanil.
Zhixiong Liao Yahui Luo Liangbin Cheng
220333444
The effects of dexmedetomidine combined with dezocine intravenous analgesia on the early postoperative cognitive function and the stress response in patients undergoing liver cancer surgery
Objective: To investigate the effects of dexmedetomidine combined with dezocine on the early postoperative cognitive function and the stress response in patients with liver cancer (LC) Methods: One hundred and nine patients admitted to the First Affiliated Hospital of Hebei North University for LC surgery from January 2016 to February 2018 were selected as the study cohort, among which 56 patients given remifentanil monotherapy were included in group A, and the remaining 53 patients were administered dexmedetomidine combined with dezocine on the basis of group A and were assigned to group B. The postoperative quality of the recovery from anesthesia, the Visual Analogue (VAS) scores, the Ramsay sedation scores, the Mini Mental State Examination (MMSE) scores, the incidence of cognitive dysfunction, the stress response indexes, and the inflammatory response indexes were observed and recorded in the two groups. Results: The cough and agitation scores in group B were markedly lower than the corresponding scores in group A (P<0.05) There were no significant differences in the VAS scores in the two groups at each time point after surgery (P>0.05) The Ramsay sedation scores in group B at 6 h and 12 h after surgery were remarkably lower than they were in group A (P<0.05) The MMSE scores in group B at 1 and 3 days after surgery were lower than the scores at 1 day before surgery (P<0.05) and at 5 days after surgery, and they were noticeably higher than the corresponding scores in group A at 1 and 3 days after surgery (P<0.05) The incidence of postoperative cognitive dysfunction in group B was notably less than it was in group A on the 1st and 3rd days after the operations (P<0.05) The postoperative levels of the stress and inflammation indexes in group B were lower than they were in group A. Conclusion: The application of dexmedetomidine and dezocine can improve the postoperative stress response and cognitive function of patients with LC.
Guoli Li Li Yuan Chaoxi Li Z Teng Jie Gong Jinliang Teng
219705022
Effects of dezocine and ropivacaine infiltration anesthesia on cellular immune function indicators, anesthesia recovery time and pain factors in patients with open liver resection.
The current experiment was carried out to explore the effects of dezocine combined with ropivacaine infiltration anesthesia on the anesthesia recovery time and pain factors of patients with open hepatectomy. A prospective randomized controlled method was used to select 92 patients with open liver cancer resection in our hospital from August 2017 to November 2019. The patients were divided into a study group (n=46) and a control group (n=46) using a computer generated random number table. Both groups underwent general anesthesia, based on this, the study group was treated with ropivacaine infiltration anesthesia 10 minutes before skin incision, and dezocine was given intravenously 0.5 h before surgery, the control group was anesthetized with ropivacaine 10 minutes before the incision, and was given a saline injection 0.5 h before the operation. Compared the recovery of anesthesia (recovery time of spontaneous breathing, time to open eyes, time to extubation) the incidence of adverse reactions, and cellular immune function indicators (peripheral blood CD4+ CD4+/CD8+ NK cell levels) stress response indicators [serum blood glucose (Glu) norepinephrine (NE) adrenaline (E) pain factors [serum dopamine (DA) neuropeptide Y (NPY) substance P (SP) before induction of anesthesia (T0) completion of surgery (T1) 12 hours after surgery (T2) and 24 hours after surgery (T3) between the two groups, and the degree of pain (VAS score) at T2 and T3 were compared between the two groups. The levels of CD4+ CD4+/CD8+ and NK cells in peripheral blood at T1, T2, and T3 in the study group were higher than those in the control group (P<0.05) serum Glu, NE, and E levels in the study group at T1, T2, and T3 were lower than those in the control group (P<0.05) serum DA, NPY, and SP levels in the study group at T1, T2, and T3 were lower than those in the control group (P<0.05) the VAS scores of the study group at T2 and T3 were lower than those of the control group (P<0.05) the time of spontaneous breathing recovery, eyes opening and extubation in the study group were shorter than those in the control group (P<0.05) the incidence of restlessness (4.35% transient hypertension (6.52% and cough (2.17% in the study group were lower than those in the control group (P<0.05) Dezocine and ropivacaine infiltration anesthesia can significantly shorten the recovery time of anesthesia and inhibit pain factor secretion in patients with open hepatectomy and can reduce the body's stress response after surgery, reduce immune function fluctuations, and can reduce the incidence of adverse reactions to anesthesia, and help promote patients' postoperative recovery.
Cellular and molecular biology
Ronggang Zhu Tingting Du Hongzhu Gao
216343752
Effect of Dezocine Combined with Dexmedetomidine on Postoperative Pain and Quality of Life in Patients with Advanced Liver Cancer
To investigate the effect of dezocine injection combined with dexmedetomidine on pain and quality of life in patients with advanced hepatocellular carcinoma. 64 patients with advanced liver cancer undergone surgery in the Central Hospital of EnshiTujia and Miao Autonomous centre from January 2016 to January 2019 were selected and randomly assigned to the experimental group and the control group. The control group was anesthetized with remifentanil during the operation and the experimental group was given remifentanil along with a combination of dezocine combined with dexmedetomidine. After the anesthesia, the time of extubating and the recovery time of the 2 groups were monitored, the visual analogue scale was used to evaluate the degree of pain in both the groups of patients at 2, 6 and 24 h, respectively and the SF 36 dimensions of 7D before and after the surgery were scored for both the groups. The incidence of adverse reactions in both the groups of patients post surgery were monitored and compared. The visual analogue scale scores of the experimental group were lower than those of the control group at 2, 6 and 24 h after surgery (p<0.05) The visual analogue scale scores at 6 and 24 h after surgery were statistically lower than those at 2 h after surgery. The extubation time, recovery time and orientation recovery time in the experimental group were all lower than those in the control group, the SF 36 dimension scores in both groups before the surgery were not significantly different. The scores of all dimensions in the experimental group were significantly higher than those in the control group post surgery. The scores of physical function, mental function and life function significantly (p<0.05) increased after intervention in both the groups. The incidence of adverse reactions was lower in the experimental group compared to the control group (p<0.05) Dezocine injection combined with dexmedetomidine could significantly relieve postoperative pain in patients with advanced hepatocellular carcinoma, shorten the recovery time and improve the quality of life.
Xiaolan Liu Y He Xiaoxia Cao Linghui Liu Hong-guang Tan
231602298
Effects of dezocine combined with propofol on cognitive function and complement levels of patients with hysteromyoma undergoing laparoscopic surgery
Objective: To determine the influence of dezocine combined with propofol on the cognitive function and complement levels of patients with hysteromyoma undergoing laparoscopic surgery. Methods: Altogether 125 patients with hysteromyoma in our hospital between March 2015 and July 2019 were enrolled, of which 67 patients were treated with dezocine combined with propofol as an observation group, while others were treated with propofol combined with remifentanil as a control group. The anesthesia indexes of the two groups were compared, and the blood pressure and heart rate (HR) of them were evaluated. Additionally, the visual analog scale (VAS) was adopted to evaluate the pain degree of patients in different time periods after operation, and the Mini Mental State Examination (MMSE) was performed to evaluate the cognitive function of the patients. The expressions of complement C3 and C4 and inflammatory factors in patients from the two groups were quantified, and the adverse reactions of them were evaluated and recorded. Results: The improvement of anesthesia indexes, blood pressure, and heart rate in the observation group was significantly better than that in the control group, and the VAS score of the observation group was lower than that of the control group at 6, 12, and 24 h after operation. Additionally, the MMSE score and C3 and C4 levels of the observation group were all significantly higher than those of the control group, and the levels of inflammatory factors and total incidence of adverse reactions in the observation group were significantly lower than those in the control group. Conclusion: For patients undergoing laparoscopic hysteromyomectomy, infusion anesthesia with both dezocine and propofol can effectively alleviate their inflammatory response, reduce their postoperative pain and postoperative complications, and improve the postoperative cognitive function and complement levels.
Xinfa Liu Juan-li Zhang Lin Jiang