糖皮质激素受体参与阿片耐受机制的研究进展

阿片药物耐受是影响临床应用阿片类药物进行疼痛治疗的主要问题.阿片药物耐受机制复杂,有许多调节因素参与其中.近年的研究提示,糖皮质激素受体在阿片耐受机制的各个环节中均发挥调节作用.如能合理利用糖皮质激素受体的这种调节作用,来找到治疗阿片耐受的突破点,将为难治性疼痛的治疗带来福音.     

Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication

We observed opioid-related respiratory depression in a patient receiving tramadol via patient-controlled analgesia. Predisposing factors were the patient's genetic background and renal impairment. Complete recovery occurred after naloxone administration, thus confirming opioid intoxication. Analysis of the patient's genotype revealed a CYP2D6 gene duplication resulting in ultra-rapid metabolism of tramadol to its active metabolite (+)O-desmethyltramadol. Concomitant renal impairment resulting in decreased metabolite clearance enhanced opioid toxicity. This genetic CYP2D6 variant is particularly common in specific ethnic populations and should be a future diagnostic target whenever administration of tramadol or codeine is anticipated, as both drugs are subject to a comparable CYP2D6-dependent metabolism.     

Tramadol: pain relief by an opioid without depression of respiration

Two independent clinical trials were conducted simultaneously. In one, tramadol and pethidine were compared in 30 patients by patient-controlled analgesia during the first 24 h following abdominal surgery. The mean 24 h consumption of tramadol and pethidine was 642 mg and 606 mg respectively, giving a potency estimate of tramadol relative to pethidine of 0.94 (95% confidence interval 0.72-1.17). In the second trial, the effect on respiration of three doses of tramadol (0.5, 1.0, and 2.0 mg.kg-1) was compared with that of morphine sulphate (0.143 mg.kg-1) by intravenous injection during stable halothane anaesthesia. At approximately 1.5 times the equipotent dose, as estimated from the first trial, tramadol transiently depressed the rate of respiration but had no effect on end-tidal carbon dioxide tension. Morphine caused apnoea or considerable depression of ventilation. The results suggest that mechanisms other than opioid receptor activity play a significant role in the analgesia produced by tramadol.     

Regulation of human sperm motility by opioid receptors

The endogenous opioid system has been reported to have important functions in human reproduction. Practically all the components of this peptide system have been discovered in human sperm cells, but their functions in these cells are far from being well understood. In the present work, we report the effects of opioid agonism and antagonism on human sperm motility, a parameter which is crucially associated with male fertility. Morphine (10(-7) M), a μ- opioid receptor agonist, decreased both the percentage of motile progressive sperm and three measured velocities without altering the linearity, straightness or vigour of sperm cells. This effect was reversed by naloxone. Higher doses of morphine did not have further effects on the measured parameters. The incubation of sperm cells with the δ-opioid receptor agonist D-penicillamine (2,5)-enkephalin did not affect sperm cell motility. However, naltrindole, a specific δ-receptor antagonist, reduced the linear and curvilinear velocities, as well as linearity, straightness and the amplitude of head displacement, and beat frequency. In summary, our results indicate that the endogenous opioid system may regulate opioid motility in vitro. These finding suggest that the endogenous opioid system could be useful as a biochemical tool for the diagnosis and treatment of male infertility.     

阿片受体、迷走神经和交感神经在瑞芬太尼诱发兔心血管抑制中的作用

目的 探讨阿片受体、迷走神经和交感神经在瑞芬太尼诱发兔心血管抑制中的作用.方法 健康新西兰白兔40只,雌雄不拘,2～6月龄,随机分为5组(n=8),R组静脉注射瑞芬太尼5.0μg/kg;N+R组静脉注射纳洛酮40μg/,2 min后静脉注射瑞芬太尼5.0μg/kg;V+R组切断颈部双侧迷走神经后,静脉注射瑞芬太尼5.0 μg/kg;S+R组行硬膜外穿刺,进行交感神经阻滞后,静脉注射瑞芬太尼5.0 μg/kg;V+S+R组切断颈部双侧迷走神经后,进行交感神经阻滞,然后静脉注射瑞芬太尼5.0μg/kg.于注射瑞芬太尼前1 min(T0)、注射后30 s(T1)、1 min(T2)、2 min(T3)、3 min(T4)、4 min(T5)、5 min(T6)、10 min(T7)、15 min(T8)、20 min(T9)时记录HR和MAP.结果 与T0时比较,各组T1时HR均减慢(P＜0.05);N+R组各时点MAP差异无统计学意义(P＞0.05),其余组T1-7时MAP均降低(P＜0.05);与R组比较,N+R组T1-7时MAP均升高(P＜0.05),其余组HR差异无统计学意义(P＞0.05).结论 瑞芬太尼减慢兔HR的机制与阿片受体、迷走神经和交感神经均无关;而其降低血压的机制与激活阿片受体有关.     

Respiratory involvement in the gastroesophageal reflux disesease

The pathological gastroesophageal reflux disease may lead to the gastroesophageal reflux disease (GERD), manifested as a spectrum of conditions including erosive esophagitis, Barrett esophagus and has been linked to the development of adenocarcinoma of the esophagus. The gastroesophageal reflux has been incriminated in the occurence of a number of pulmonary symptoms and diseases, otolaryngologic symptoms, and other extraesophageal manifestations. Clinicians must be aware of the possibility of some extraesophageal reflux-related manifestations, even in the absence of heartburn and acid reflux, classic esophageal symptoms of GERD. Although the correlation between gastroesophageal reflux disease and the extraesophageal manifestations has been established, a cause-and-effect relationship has not been proved yet. In this article, we present the respiratory manifestations of gastroesophageal reflux disease, referring to epidemiology, pathogenesis, diagnosis and treatment.     

Respiratory depression after morphine in the elderly

The effects of intravenous morphine (10 mg/70 kg) on the ventilatory response to CO2 were studied in two groups of subjects, young (18-29 years) and old (66-85 years), prior to elective surgery. In both groups morphine caused a significant depression of respiration as judged by a reduction in the slope of the CO2 response curve, a reduction in the calculated ventilation at an end tidal CO2 tension of 7.3 kPa, a rise in resting end tidal CO2 and a rise in the CO2 threshold. There were no significant differences between the two groups in the changes produced by the drug, suggesting that acute respiratory depression after a single intravenous injection of morphine is similar in old and young people.     

Mu opioid receptors in pain management

Most of the potent analgesics currently in use act through the mu opioid receptor. Although they are classified as mu opioids, clinical experience suggests differences among them. The relative potencies of the agents can vary from patient to patient, as well as the side-effect profiles. These observations, coupled with pharmacological approaches in preclinical models, led to the suggestion of multiple subtypes of mu receptors. The explosion in molecular biology has led to the identification of a single gene encoding mu opioid receptors. It now appears that this gene undergoes extensive splicing, in which a single gene can generate multiple proteins. Evidence now suggests that these splice variants may help explain the clinical variability in responses among patients.     

Effects of azepexole on opioid receptors and endogenous opioid release in the guinea pig ileum

The interactions of the opioid and adrenergic systems were investigated in the guinea pig myenteric plexus longitudinal muscle preparation. Morphine and azepexole (a highly selective alpha 2-adrenergic agonist) inhibit the electrically induced contractions with ED50 of 1.9 X 10(-7) M and 3.1 X 10(-6) M, respectively. The effect of morphine but not that of azepexole was competitively antagonized by naloxone. Stimulation of the preparation at 10 Hz was used to induce endogenous opioid release that was unaffected by azepexole. The authors' findings indicate that the effects of morphine and azepexole are additive, but that there is no direct interaction between the opioid and adrenergic receptors in the ileum. These observations provide some additional insight into the ability of alpha 2-agonists to enhance the effects of opioids and inhalation anesthetics.     

Respiratory depression after neuraxial opioids in the obstetric setting

Neuraxial opioids have contributed significantly to improved labor and postcesarean delivery analgesia. In the obstetric population, epidural and intrathecal opioids are associated with a very low risk of clinically significant respiratory depression. Although rare, respiratory depression is a serious risk; patients may die or suffer permanent brain damage as a consequence. This review discusses the mechanism and incidence, as well as the prevention, detection, and management of respiratory depression with morphine, extended-release epidural morphine, and lipophilic opioids in the labor and cesarean delivery setting.