Comparison between pentazocine, pethidine and placebo in the treatment of post-anesthetic shivering

BACKGROUND: We have compared the effects of pethidine, pentazocine and placebo in the treatment of post-anesthetic shivering. METHODS: Forty-five patients who shivered after routine surgery were allocated randomly to receive normal saline (n=15), pentazocine 7.5 mg (n=15) or pethidine 17.5 mg (n=15). RESULTS: After 10 min, 13 patients had stopped shivering in the pethidine group, which was significantly more than the incidence in the two other groups (placebo=2; pentazocine=4) (P<0.01). Pentazocine was not significantly different from normal saline in affecting shivering. CONCLUSION: We conclude that pentazocine 7.5 mg was not effective in the treatment of post-anesthetic shivering.     

Continuous epidural analgesia with bupivacaine-fentanyl versus patient-controlled analgesia with i.v. morphine for postoperative pain relief after knee ligament surgery

BACKGROUND: Both epidural analgesia and intravenous patient-controlled analgesia (PCA) have been found efficacious after various types of surgery. We compared the efficacy, safety, side effects and patient satisfaction of these methods in a randomized double-blind fashion after elective anterior cruciate ligament reconstruction of the knee. METHODS: Fifty-six patients had an epidural catheter placed at the L2-L3 interspace. Spinal anaesthesia with 15 mg of plain bupivacaine 5 mg/ml was performed at the L3-L4 interspace. After surgery the patients were randomly divided into three groups: 19 received a continuous epidural infusion with bupivacaine 1 mg/ml and fentanyl 10 mg/ml (F10), 19 patients received bupivacaine 1 mg/ml and fentanyl 5 microg/ml (F5) and 18 patients received saline (S). The rate of the epidural infusions was 0.1 ml kg(-1) h(-1). Each patient could also use an intravenous (i.v.) PCA device with 40 microg/kg bolus doses of morphine with a lockout period of 10 min and a maximum dose 240 microg kg(-1) h(-1). At the end of surgery ketoprofen 100 mg i.v. was given and continued orally three times a day. Patients were assessed for pain with a visual analogue scale (VAS) at rest and during activity, side effects and satisfaction at 3, 9 and 20 h. RESULTS: Both epidural infusions (F10, F5) provided better analgesia than epidural saline plus i.v. PCA (S) (P<0.05). There was slightly less nausea in the S group (NS). In spite of the difference in the quality of pain relief, there was no difference between the groups in patient satisfaction regarding analgesic therapy. CONCLUSION: Epidural infusion of fentanyl (1 microg kg(-1) h(-1) or 0.5 microg kg(-1) h(-1)) and bupivacaine (0.1 mg kg(-1) h(-1)) provided better pain relief but more side effects than intravenous morphine patient-controlled analgesia after knee ligament surgery. Almost all patients in all groups were satisfied with their pain relief.     

Day-case laparoscopy: a comparison of prophylactic opioid, NSAID or local anesthesia for postoperative analgesia

BACKGROUND: The study was aimed to evaluate the analgesic efficacy, postoperative comfort, recovery characteristics and side effects of three different analgesic agents administered prophylactically. METHODS: Eighty patients undergoing day-case minor operative laparoscopy were randomly allocated into four groups to receive tenoxicam 20 mg i.v. (Group T), fentanyl 100 microg i.v. (Group F), 5 ml of bupivacaine 2.5 mg/ml for infiltration of trocar sites (Group B), 30, 10 and 5 min before incision respectively. Bupivacaine, 35 ml, 2.5 mg/ml was also administered into the pelvic cavity in Group B. Group P received only placebo. Postoperative pain, analgesic requirements, first response to verbal stimulus, first analgesic requirement, ability to walk without help, to drink and to void, blood pressures, SpO2 and respiration rates were recorded in the PACU. Postoperative pain was evaluated by verbal rating scale. Pain scores, analgesic requirements and side effects were evaluated by telephone calls until the 48th postoperative hour. RESULTS: Postoperative pain scores were lower and time to requirement of rescue analgesics was longer in groups F and B compared to Group P. In the PACU, analgesic requirements were lower in Group B, compared to Group P. Nausea and vomiting were increased in Group F. CONCLUSION: Tenoxicam 20 mg i.v. was found to be ineffective whereas bupivacaine was superior to other groups in reducing pain and analgesic requirements. Bupivacaine also increased time to first analgesics and obtained better recovery characteristics, underlining its value in prophylactic pain management compared to the other two agents.     

μ-阿片受体参与介导丘脑中央下核内吗啡抑制的诱发性炎性痛

目的：探明丘脑中央下核（Sm）内给予吗啡诱发大鼠炎性痛抑制效应的阿片受体类型。方法：建立福尔马林诱发炎性疼痛的动物模型，神经核团内微量注射拟定药物，采用福尔马林试验人工评分法进行疼痛分数评价。结果：福尔马林诱发的晚时相反应（炎性持续痛）的疼痛分数值可因单侧Sm内供给吗啡（5．0μg，0．5μL）后明显变小（抑制作用），μ-阿片受体拮抗剂（β-FNA，0．1μg）可完全翻转吗啡诱发的抑制效应。δ-阿片受体拮抗剂（naltrindole，0．3μg）和κ-阿片受体拮抗剂（nor-binaltorphimine，0．1μg）均不能取消吗啡产生的抑制效应。结论：Sm内给予吗啡产生的抗炎性痛效应是由μ-阿片受体介导的。     

毕赤酵母表达阿片肽发酵条件的研究

研究了由毕赤酵母胞内两步发酵法表达活性小分子阿片肽的条件.正交实验确定最佳生长条件为:甘油24g/L、酵母膏11g/L、蛋白胨22g/L、YNB 20ml/L,初始pH5.0.菌体密度可达2.46;以单因素实验确定最佳表达条件为:起始菌体浓度2.44,初始pH 6.25,每10h流加0.6%甲醇(v/v),表达时间96h.阿片肽250ml摇瓶产量由196mg/L提高至496mg/L.     

Structure–activity relationships of arodyn,a novel acetylated kappa opioid receptor antagonist*,†

Abstract: We previously reported that the novel dynorphin A (Dyn A, Tyr‐Gly‐Gly‐Phe‐Leu‐Arg‐Arg‐Ile‐Arg‐Pro‐Lys‐Leu‐Lys‐Trp‐Asp‐Asn‐Gln) analog arodyn (Ac[Phe^1,2,3,Arg⁴,d ‐Ala⁸]Dyn A‐(1–11)NH₂, Bennett, M.A., Murray, T.F. & Aldrich, J.V. (2002) J. Med. Chem. vol. 45, pp. 5617–5619) is a κ opioid receptor‐selective peptide [K_i(κ) = 10 nm , K_i ratio (κ/μ/δ) = 1/174/583] which exhibits antagonist activity at κ opioid receptors. In this study, a series of arodyn analogs was prepared and evaluated to explore the structure–activity relationships (SAR) of this peptide; this included an alanine scan of the entire arodyn sequence, sequential isomeric d ‐amino acid substitution in the N‐terminal ‘message’ sequence, NMePhe substitution individually in positions 1–3, and modifications in position 1. The results for the Ala‐substituted derivatives indicated that Arg⁶ and Arg⁷ are the most important residues for arodyn's nanomolar binding affinity for κ opioid receptors. Ala substitution of the other basic residues (Arg⁴, Arg⁹ and Lys¹¹) resulted in lower decreases in affinity for κ opioid receptors (three‐ to fivefold compared with arodyn). Of particular interest, while [Ala¹⁰]arodyn exhibits similar κ opioid receptor binding as arodyn, it displays higher κ vs. μ opioid receptor selectivity [K_i ratio (κ/μ) = 1/350] than arodyn because of a twofold loss in affinity at μ opioid receptors. Surprisingly, the Tyr¹ analog exhibits a sevenfold decrease in κ opioid receptor affinity, indicating that arodyn displays significantly different SAR than Dyn A; [Tyr¹]arodyn also unexpectedly exhibits inverse agonist activity in the adenylyl cyclase assay using Chinese hamster ovary cells stably expressing κ opioid receptors. Substitution of NMePhe in position 1 gave [NMePhe¹]arodyn which exhibits high affinity [K_i(κ) = 4.56 nm ] and exceptional selectivity for κ opioid receptors [K_i ratio (κ/μ/δ) = 1/1100/>2170]. This peptide exhibits antagonistic activity in the adenylyl cyclase assay, reversing the agonism of 10 nm Dyn A‐(1–13)NH₂. Thus [NMePhe¹]arodyn is a highly κ opioid receptor‐selective antagonist that could be a useful pharmacological tool to study κ opioid receptor‐mediated activities.     

Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient

A 25-year-old man suffered from consciousness change was sent to our emergency department by friends who reported that they were not sure what had happened to him. Physical examination revealed bilateral pupils dilatation, lethargy, slurred speech, and ataxia. Computer-aided tomographic scan of the brain revealed no definite evidence of intracranial lesions. Routine laboratory tests revealed total physiological turmoil. Despite immediate commencement of aggressive treatment, the patient's condition deteriorated long before the traditional drug screen provided an answer for the identities of the multiple drugs overdose. It ended up with the need for cardiopulmonary resuscitation, but in vain. At the end of the tragic event, under the suggestion of a colleague, a portion of the patient's urine specimen was sent to our university esoteric laboratory for rapid analysis by means of a newly-developed thermal desorption-electrospray ionization-mass spectrometry. Ketamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyamphetamine were identified in the urine sample within 30 s. Conventional toxicological testing techniques like gas chromatography–mass spectrometry or liquid chromatography-mass spectrometry are currently used for identifying abused drugs. One concern is their time-consuming sample pretreatment which leads to relatively low efficiency in terms of turnaround time for revealing the identity of the consumed drugs particularly when the patients are severely overdosed. We learned a lesson from this case that a more efficient toxicological identification technique is essential to expedite the process of emergency care when the patients are so heavily overdosed that they are under critical life-threatening conditions.     

High enhancer,downer, withdrawal helper: Multifunctional nonmedical benzodiazepine use among young adult opioid users in New York City

BackgroundBenzodiazepines are a widely prescribed psychoactive drug; in the U.S., both medical and nonmedical use of benzodiazepines has increased markedly in the past 15 years. Long-term use can lead to tolerance and dependence, and abrupt withdrawal can cause seizures or other life-threatening symptoms. Benzodiazepines are often used nonmedically in conjunction with other drugs, and with opioids in particular—a combination that can increase the risk for fatal and non-fatal overdose. This mixed-methods study examines nonmedical use of benzodiazepines among young adults in New York City and its relationship with opioid use.MethodsFor qualitative analysis, 46 90-minute semi-structured interviews were conducted with young adult opioid users (ages 18–32). Interviews were transcribed and coded for key themes. For quantitative analysis, 464 young adult opioid users (ages 18–29) were recruited using Respondent-Driven Sampling and completed structured interviews. Benzodiazepine use was assessed via a self-report questionnaire that included measures related to nonmedical benzodiazepine and opioid use.ResultsParticipants reported using benzodiazepines nonmedically for a wide variety of reasons, including: to increase the high of other drugs; to lessen withdrawal symptoms; and to come down from other drugs. Benzodiazepines were described as readily available and cheap. There was a high prevalence (93%) of nonmedical benzodiazepine use among nonmedical opioid users, with 57% reporting regular nonmedical use. In bivariate analyses, drug-related risk behaviours such as polysubstance use, drug binging, heroin injection and overdose were strongly associated with regular nonmedical benzodiazepine use. In multivariate analysis, growing up in a middle-income household (earning between $51,000 and $100,000 annually), lifetime overdose experience, having ever used cocaine regularly, having ever been prescribed benzodiazepines, recent drug binging, and encouraging fellow drug users to use benzodiazepines to cope with opioid withdrawal were consistently strong predictors of regular nonmedical benzodiazepine use.ConclusionNonmedical benzodiazepine use may be common among nonmedical opioid users due to its drug-related multi-functionality. Harm reduction messages should account for the multiple functions benzodiazepines serve in a drug-using context, and encourage drug users to tailor their endorsement of benzodiazepines to peers to include safer alternatives.     

Use of Street Methadone in Italian Heroin Addicts Presenting for Opioid Agonist Treatment

ABSTRACT

It is commonly assumed that people who are addicted to certain substances would abuse any substance. This position has never been supported by validly collected and analyzed research data. In this study, the authors examine the use of street methadone by heroin addicts seeking their first agonist opioid treatment in a clinical setting. Fifty-four heroin addicts who resorted to street methadone use were compared by socio-demographic, current clinical, and disease-related variables to 251 peers who do not use street methadone. Heroin addicts who resort to street methadone use are more likely to be females and to have a higher degree of education, are less likely to engage in polyabuse (use of more than three substances), are less severely ill, have been addicted for a shorter period of time, and have been seeking treatment sooner in the course of their disease. Also, they suffer from a wider range of psychopathological distress symptoms. In Italy, resorting to street methadone does not seem to be a surrogate form of heroin addiction, but rather represents means of harm reduction, with treatment seeking occurring shortly after its initiation. This should be accounted for when deciding on take-home policies and issues of potential methadone diversion.