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     

Effects of diazepam and hydromorphone in triazolam-trained humans under a novel-response drug discrimination procedure

Seven healthy normal male and female volunteers (21–31 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg, PO; e.g., drug A) and placebo (e.g., drug B) under a three-choice, instructed novel response drug discrimination procedure. Once the criterion for discrimination was met (i.e., >85% correct responding on four consecutive sessions), dose-effect curves were determined for triazolam (0.1–0.56 mg/70 kg), the benzodiazepine diazepam (10–32 mg/70 kg) and the opioid agonist hydromorphone (1–6 mg/70 kg). Subjects met the criterion for discrimination within four to six sessions. Triazolam and diazepam produced dose-related increases in triazolam-appropriate responding and no novel-appropriate responding at any dose tested. In contrast, hydromorphone generally increased novel-appropriate responding in a dose-related manner, with placebo-appropriate responding and some triazolam-appropriate responding at intermediate doses occurring also. Triazolam and diazepam produced qualitatively similar increases on several measures of sedative drug effects; hydromorphone increased ratings of like novel and sedative-like effects in subjects who discriminated hydromorphone as novel relative to those who did not. These results indicate that the novel response drug discrimination procedure enhances the specificity of the triazolam-placebo discrimination.This work was supported by USPH grants DA-06205, T32-DA-07242 and Research Scientist Development Award DA-00109 (J.R.H.) from the National Institute on Drug Abuse.     

氢吗啡酮复合罗哌卡因用于胸腹腔镜联合食道癌根治术后硬膜外自控镇痛的效果观察

目的观察氢吗啡酮复合罗哌卡因用于胸腹腔镜联合食道癌根治术后硬膜外自控镇痛(PCEA)的效果及安全性。方法选择浙江省台州医院拟在全身麻醉复合硬膜外麻醉下行胸腹腔镜联合食道癌根治术的患者60例,随机分为氢吗啡酮复合罗哌卡因PCEA组(H组)和舒芬太尼复合罗哌卡因PCEA组(S组),每组各30例。H组:氢吗啡酮10μg/mL+罗哌卡因1.25 mg/mL;S组:舒芬太尼0.3μg/mL+罗哌卡因1.25 mg/mL。给药方案:负荷剂量为6 m L,维持剂量4 mL/h,自控剂量每次5 mL,锁时30 min。记录术后4、8、12、24和48 h静息和咳嗽时的视觉模拟评分(VAS)及下肢运动神经阻滞程度(改良Bromage分级)。记录术后48 h内PCEA的有效按压次数(D1)和实际按压次数(D2),并计算D1/D2,以评价镇痛满意度。记录术后48 h内不良反应发生情况和镇痛补救情况,并计算镇痛补救率。结果 H组术后4、8、12、24和48 h静息和咳嗽时VAS评分明显较S组低(P 0.05)。H组术后48 h内PCEA的D1、D2和镇痛补救率明显低于S组(P 0.05),D1/D2和镇痛满意度明显高于S组(P 0.05)。两组患者术后4、8、12、24和48 h的改良Bromage分级和术后48 h内不良反应发生情况比较,差异均无统计学意义(P 0.05)。结论氢吗啡酮复合罗哌卡因用于胸腹腔镜联合食道癌根治术后,PCEA效果确切,不良反应少,且镇痛效果优于舒芬太尼复合罗哌卡因,患者满意度更高。     

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。     

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.     

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.     

氟比洛芬酯联合氢吗啡酮在老年髋/膝关节置换术后患者自控静脉镇痛中的应用效果

目的:观察氟比洛芬酯联合氢吗啡酮在老年髋/膝关节置换术(THA/KTA)后患者自控静脉镇痛(PCIA)中的应用效果。方法:选取接受THA/KTA的70例老年患者作为研究对象,按照随机数字表法分为对照组和观察组各35例。术后对照组予以盐酸氢吗啡酮注射液镇痛,观察组在对照组的基础上联合氟比洛芬酯注射液镇痛,比较两组术后4、12、24、48 h视觉模拟评分法(VAS)评分,术前及术后24 h炎性因子[白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)]水平,以及不良反应发生率。结果:术后12、24、48 h时,观察组VAS评分均明显低于对照组,差异有统计学意义(P<0.05);术后24 h,观察组IL-6、IL-1β、TNF-α水平均明显低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:氟比洛芬酯联合氢吗啡酮应用于老年THA/KTA术后患者自控静脉镇痛中,可降低术后VAS评分和炎性因子水平,效果优于单纯氢吗啡酮镇痛。     

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.     

腹腔镜肝切除术治疗原发性肝癌患者应用氢吗啡酮联合纳布啡静脉自控镇痛控制疼痛作用研究*

目的 探讨腹腔镜肝切除术(LH)治疗原发性肝癌(PLC)患者应用氢吗啡酮联合纳布啡静脉自控镇痛(PCIA)控制疼痛的效果。方法 2018年1月～2021年1月我院收治的PLC患者104例,随机分为对照组52例和观察组52例,两组患者均接受LH手术,在对照组,给予舒芬太尼联合纳布啡用于术后PCIA,而在观察组给予氢吗啡酮联合纳布啡用于术后PICA。采用疼痛视觉模拟评分(VAS)评价术后疼痛程度,使用流式细胞仪检测外周血T细胞亚群CD3⁺细胞、CD4⁺细胞、CD8⁺细胞和NK细胞百分比。结果 在术后24 h,观察组静态VAS和动态VAS分别为(2.5±0.8)分和(3.7±1.2)分,显著低于对照组【分别为(4.3±1.2)分和(5.8±1.7),P＜0.05】,在术后72 h,静态VAS和动态VAS分别为(1.1±0.4)分和(3.2±0.9)分,显著低于对照组【分别为(2.6±0.7)分和(5.1±1.3),P＜0.05】;术后,两组肝功能指标变化无显著性差异(P＞0.05);在术后7 d,观察组外周血CD3⁺细胞、CD4⁺细胞、CD8⁺细胞和NK细胞百分比分别为(76.3±7.5)%、(36.8±4.9)%、(32.5±3.2)%和(16.3±2.9)%,与对照组【分别为(75.2±7.4)%、(37.6±4.4)%、(31.2±3.4)%和(17.4±2.6)%】比,差异无统计学意义(P＞0.05)。结论 氢吗啡酮联合纳布啡用于LH后PCIA能够有效减轻患者疼痛程度。     

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.