Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers

Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained on daily sublingual (SL) buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of buprenorphine, and consisted of double-blind IM injections of buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects’ self-reports, and a trained observer’s ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that buprenorphine’s combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance buprenorphine plus challenge buprenorphine without adverse effects, suggesting higher doses of buprenorphine can be safely administered to opioid dependent patients. Received: 22 February 1996/Final version: 23 August 1996     

连续股神经阻滞联合盐酸氢吗啡酮在全膝关节置换术后的镇痛效果观察

目的 探讨在人工全膝关节置换术(total knee arthroplasty,TKA)术后连续股神经阻滞联合盐酸氢吗啡酮镇痛的效果.方法 ASA Ⅰ～Ⅱ级行单侧人工全膝关节置换手术的患者42例,经患者知情同意后,将42例患者按照数字表法分为对照组(连续股神经阻滞镇痛)和观察组(连续股神经阻滞联合盐酸氢吗啡酮镇痛),每组21例.2组患者均在连续硬膜外麻醉下实施手术,硬膜外穿刺成功推注2％利多卡因试验量测出平面后,经股神经鞘放置导管并固定好导管,术毕对照组采用0.2％罗哌卡因持续泵注6 ml/h;观察组采用盐酸氢吗啡酮2 mg +0.3％罗哌卡因持续泵注2 ml/h.记录术后静息状态下6、12、24、36、48 h的疼痛评分和术后24、36、48 h功能锻炼时疼痛评分及并发症的发生率.结果 观察组患者的疼痛评分(视觉模拟评分VAS)无论是在静息状态下还是在功能锻炼时均比对照组低,2组比较差异有统计学意义(P＜0.05);对照组股神经穿刺点局部水肿的发生率明显高于观察组,差异有统计学意义(P＜0.05).结论 连续股神经阻滞联合盐酸氢吗啡酮镇痛可为人工全膝关节置换术的患者提供更为满意的镇痛效果.     

Efficacy of patient-controlled hydromorphone analgesia in those undergoing uterine fibroid artery embolization via the right radial artery

ObjectiveTo evaluate the efficacy and safety of patient-controlled analgesia (PCA) with hydromorphone as perioperative analgesia during uterine artery embolization (UAE) via the right radial artery.Patients and methodsA total of 33 patients with uterine fibroids, who underwent UAE at the authors’ hospital between June 2021 and March 2022, were selected. Hydromorphone (10 ​mg) was dispensed into a 100 ​ml PCA pump with normal saline. Pump administration was initiated 15 ​min before the start of the procedure, and the intraoperative dose was adjusted according to patient pain level. A numerical rating scale was used to evaluate pain immediately after embolization, 5 ​min after embolization, at the end of the procedure, and 6, 12, 24, 48, and 72 ​h after the procedure. Side effects were also observed.ResultsThirty-three patients underwent uterine artery embolization via the right radial artery. Patient pain was well controlled at all time points surveyed, and patients reported satisfaction with analgesia. The median length of hospital stay was 5 days. There were 7 cases of adverse reactions, but no serious side effects were observed.ConclusionPatients reported positive experiences with arterial embolization of uterine fibroids via the right radial artery. Hydromorphone PCA effectively controlled pain. The PCA pump is easy to operate, has a low incidence of adverse reactions, and offers economic benefits at the patient and institutional levels.     

氢吗啡酮和芬太尼对全麻诱导气管插管应激反应的影响

目的：：比较盐酸氢吗啡酮和芬太尼对全麻诱导气管插管应激反应的影响。方法：择期全麻行口腔颌面部良性肿物切除术的患者60例,随机分为三组。建立静脉通路后,H1组、H2组、F组患者分别静脉注射氢吗啡酮0.2mg、0.4mg和芬太尼0.2mg,5min之后常规诱导气管插管。记录患者入室后5min(T0),插管前即刻(T1),插管即刻(T2),插管后1min(T3)、3min(T4)、5min(T5)、10min(T6)的平均动脉压(MAP)和心率(HR)。结果：三组药物对MAP、HR的影响存在组间差异,其中H2组不同时相MAP、HR较平稳。结论：0.4mg盐酸氢吗啡酮和0.2mg芬太尼均能有效减弱全麻气管插管引起的应激反应,且0.4mg盐酸氢吗啡酮在不同时相对患者MAP、HR的影响更小,全麻诱导插管更为平稳。     

氢吗啡酮预处理对大鼠视网膜缺血-再灌注损伤的影响

目的观察氢吗啡酮预处理对大鼠视网膜缺血-再灌注损伤的影响,并探讨其作用机制。方法SPF级SD大鼠48只,随机分为假手术组(C组)、缺血-再灌注组(IR组)、氢吗啡酮组(H组)和吗啡组(M组),每组12只。采用前房加压灌注的方法制备视网膜缺血-再灌注损伤模型。于缺血前15 min,H组颈内静脉注射氢吗啡酮0.1mg/kg,M组注射吗啡1mg/kg,C组和IR组注射等容量生理盐水。再灌注24 h后,取大鼠视网膜组织,采用HE染色法观察病理学变化,测定视网膜内层厚度及全层厚度;采用TUNEL法计算细胞凋亡指数(AI);采用免疫组化法检测Bax、Bcl-2、caspase-3蛋白含量;采用ELISA法检测TNF-α、IL-6浓度;采用硫代巴比妥酸及黄嘌呤氧化酶法分别检测MDA浓度和SOD活性。结果与C组比较,IR组视网膜出现病理学损伤,AI明显升高(P<0.05);Bax、caspase-3蛋白含量明显升高,Bcl-2蛋白含量和Bcl-2/Bax比值明显降低(P<0.05);TNF-α、IL-6和MDA浓度明显升高(P<0.05),SOD活性明显减弱(P<0.05)。与IR组比较,H组和M组视网膜组织病理学损伤明显减轻,AI明显降低(P<0.05);Bax、caspase-3蛋白含量明显降低,Bcl-2蛋白含量明显升高,Bcl-2/Bax比值明显升高(P<0.05);TNF-α、IL-6和MDA浓度明显降低,SOD活性明显增强(P<0.05)。结论氢吗啡酮可减轻大鼠视网膜缺血-再灌注损伤,其机制可能与改善视网膜细胞凋亡、炎症反应及氧化应激相关。     

硬膜外腔注射氢吗啡酮在剖宫产术后镇痛的临床观察

目的 观察硬膜外腔注射不同剂量盐酸氢吗啡酮对剖宫产术后镇痛的效果和安全性.方法 选择单胎足月于硬膜外麻醉下行剖宫产手术的初产妇60例,按随机数字表法分为A组、B组、C组,每组20例.3组分别于术毕前10 min经硬膜外腔注射5 ml生理盐水稀释的盐酸氢吗啡酮0.1、0.2、0.3 mg.记录术后3、6、12、24 h的疼痛VAS评分,24 h镇痛药物追加的例数及术后副作用发生的情况.结果 术后6、12、24 h的VAS评分C组低于A、B两组,B组低于A组(P＜0.05);镇痛药追加例数C组(2例)少于A组(8例)(P＜0.05);副作用组间比较差异无统计学意义(P＞0.05).结论 硬膜外腔内注射不同剂量的盐酸氢吗啡酮用于剖宫产术后早期可获得良好的镇痛效果,0.3 mg的盐酸氢吗啡酮效果更佳.     

Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in healthy volunteers

RATIONALE: The psychopharmacological profile of hydromorphone, an opioid that has been used extensively for many years for post-operative pain management, has not been adequately characterized in non-drug abusers. OBJECTIVES: To characterize the subjective, psychomotor, and physiological effects of a range of single doses of hydromorphone in non-drug-abusing volunteers and to compare the effects of hydromorphone with that of morphine, a benchmark mu opioid agonist. METHODS: Subjects in a six-session study were injected in an upper extremity vein with 0, 0.33, 0.65, 1.3 mg/70 kg hydromorphone, and 5 and 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. RESULTS: Hydromorphone increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of ("dry mouth", "flushing", and "nodding", and increased visual analog scale ratings indicative of both pleasant (e.g., drug liking) and unpleasant (e.g., "feel bad") effects. The subjective effects of morphine at putatively equianalgesic doses to those of hydromorphone were similar to those of hydromorphone, but in some cases of lesser magnitude. Psychomotor impairment was modest with hydromorphone and absent with morphine. Both opioids produced dose-dependent decreases in pupil size. A relative potency analysis indicated that hydromorphone was 10 times as potent as morphine (1 mg hydromorphone=10 mg morphine). CONCLUSIONS: The results of this study demonstrate that 0.33-1.3 mg hydromorphone had orderly, dose-related effects on subjective, psychomotor, and physiological variables, and similar effects to those of a benchmark mu opioid agonist, morphine.     

人血浆中氢吗啡酮的LC-MS测定方法及其应用

目的:建立人血浆中氢吗啡酮的LC-MS测定法,并研究术后镇痛患者恒速静脉泵注盐酸氢吗啡酮后氢吗啡酮的药代动力学特征。方法:血浆样品经碱化乙酸乙酯提取后,进行LC-MS分析,流动相为甲醇-5 mmol·L-1醋酸铵水溶液(含1%甲酸)(12∶88,v/v)。氢吗啡酮检测离子为[M+H]+m/z 286.2,内标(纳洛酮)检测离子为[M+H]+m/z 328.2。测定手术后镇痛患者恒速静脉泵注盐酸氢吗啡酮注射液1.5 mg后血浆中氢吗啡酮的浓度,并计算主要药动学参数。结果:在0.06～60 ng·mL-1范围内,线性关系良好;批内批间精密度RSD均小于10%;提取回收率为68.8%～75.7%。结论:本方法可用于氢吗啡酮人体药动学研究。     

Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence of alcohol

ABSTRACT

Objective: The purpose of this study was to investigate the pharmacokinetic properties of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) in the presence of alcohol.

Research design and methods: In a single-centre, open-label, four-treatment, four-period, four-sequence, crossover study, two groups of 24 healthy subjects (fasted or fed) were randomised to receive four single doses of OROS hydromorphone 16?mg with solutions of either 0%, 4%, 20% or 40% alcohol, and with a naltrexone block.

Main outcome measures: Plasma samples taken predose and at regular intervals up to 48?h after dosing were assayed for hydromorphone concentrations; a mixed-effect analysis of variance was done on log-transformed data. Bioequivalence was concluded if 90% confidence intervals of treatment mean ratios were between 80% and 125%.

Results: Plasma hydromorphone concentrations were slightly higher after dosing with all alcohol treatments in both the fasted and fed subject groups. Median T_max values were between 12 and 16?h and ranges were similar for all treatments. C_max values increased after alcohol compared with no alcohol, with the increase slightly lower in the fed state. The greatest mean increase in C_max observed was 1.3-fold in the fasted state and 1.1-fold in the fed state. Confidence intervals were within 80–125% for AUC but were slightly higher for C_max.

Conclusions: The pharmacokinetics of once-daily OROS hydromorphone were only minimally affected by alcohol, with no dose dumping of hydromorphone. The results indicate that the controlled-release properties of this formulation are maintained in the presence of alcohol.