治疗镰状红细胞病新药voxelotor

摘要：镰状细胞病（SCD）是一种由β-珠蛋白基因突变引起的常染色体隐性遗传病,受损的红细胞阻塞毛细血管并发生溶血,贫血、组织缺血、痛性血管闭塞危象（VOC）、血管损伤和器官损伤。Voxelotor为镰状血红蛋白（HbS）聚合抑制药,通过调节血红蛋白对氧的亲和力,从而抑制HbS聚合,改善溶血性贫血和血管阻塞的下游不良反应来治疗SCD。临床试验显示voxelotor治疗SCD安全、有效,不良反应轻微。本文就其药理作用、药动学、临床试验、不良反应及药物相互作用进行综述。     

高乌甲素与曲马多分别复合芬太尼术后镇痛作用比较（附60例分析）

阿片类麻醉性镇痛药是治疗术后疼痛最有效的药物,但因其特有的不良反应,临床上常与其他非阿片类镇痛药复合以减少药物剂量,减少不良反应,提高镇痛质量,利于术后康复。本研究将高乌甲素与曲马多,分别复合芬太尼用于腹部外科术后,静脉自控镇痛（PCIA）,观察两者镇痛效果、不良反应及安全性。     

注射用帕瑞昔布的药理作用与临床应用

帕瑞昔布是由瑞典法玛西亚公司和美国辉瑞公司联合推出的一种注射用选择性环氧酶（eyclooxygenase,COX）-2抑制剂,用于预防和治疗中重度术后疼痛。目前临床上用于镇痛的药物主要有阿片类药和非甾体抗炎药。     

舒芬太尼和氯诺昔康在妇科微创手术后自控静脉镇痛的比较

舒芬太尼是一种强效阿片类药,镇痛效果强[1]。氯诺昔康是一种非甾体类抗炎药,具备阿片类镇痛作用,可用于术后急性中度疼痛治疗。为更好地确定舒芬太尼和氯诺昔康的镇痛效果,现对妇科微创手术后患者单独与复合使用两种药物自控静脉镇痛（PCIA）的镇痛效果及不良反应进行分析,报道如下。     

凯纷注射液联合美施康定治疗重度癌性疼痛的疗效观察

目的：观察凯纷注射液（氟比洛芬酯脂微球注射液）联合美施康定（硫酸吗啡控释片）治疗重度癌性疼痛的镇痛效果及不良反应情况。方法：60例未使用过强阿片类药物的癌痛患者随机分为两组,单纯组口服美施康定治疗,联合组静脉滴注凯纷注射液联合口服美施康定治疗,连续观察10d为一疗程,疗程结束后分别就其治疗后疼痛缓解效果、阿片类剂量滴定、生活质量改善及不良反应等方面进行评价。结果：单纯组与联合组均能达到满意的镇痛效果,差异无显著性（P〉0．05）,但联合组在减少阿片类止痛药剂量、提高患者生活质量及减轻阿片类药物引起恶心、便秘发生率明显优于单纯组,具有显著差异（P〈0．05）。结论：凯纷注射液与美施康定联合使用治疗重度癌痛,可减少阿片类药物用量,减少镇痛药物所引起的胃肠道反应,并提高患者生活质量。     

帕瑞昔布钠的超前镇痛应用现状

帕瑞昔布钠（Parecoxib sodium）是一种选择性环氧化酶-2（Cyclooxygenase-2,COX-2）抑制剂,可用于围术期急性疼痛的治疗,经临床观察其镇痛效果确切,应用于围术期以降低阿片类药的使用剂量及相关不良反应,提高患者的满意度,进而控制外科手术或创伤的急性疼痛。本文对帕瑞昔布钠在各种手术中的超前镇痛应用情况、术后镇痛效果等进行综述。     

盐酸氢吗啡酮的临床研究进展

盐酸氢吗啡酮（hydromorphone）作为一种强效阿片类镇痛药物，在临床上已有八十余年的历史。盐酸氢吗啡酮是半合成阿片类药物，它通过激动中枢神经系统μ-阿片类受体起到镇痛作用。吗啡作为阿片类药物的代表一直被广泛应用于癌性疼痛镇痛和术后镇痛，而盐酸氢吗啡酮在化学结构上的变化使其在理化性质、临床镇痛应用等方面均优于传统吗啡。现就该药的实验研究和在各领域的应用予以综述。     

阿片受体激动剂的镇痛作用及其靶点通路研究进展

疼痛是一种复杂的生理现象,目前主要运用药物进行镇痛.阿片类受体激动剂类镇痛药受到了越来越多的关注,阿片受体及其与药物的作用机制研究取得了较大发展,近年来逐渐被用于临床治疗疼痛,但由于没有研究可以对其镇痛以及成瘾的机制进行明确地阐释,因此阿片受体激动剂在临床上没有得到广泛应用.探讨阿片类受体的结构特点和作用机制,并在此基础上开发结构全新或新作用机制的镇痛药物,是推动阿片类受体激动剂在临床上用于镇痛治疗的前提.综述阿片类受体激动剂在镇痛方面的应用及其信号通路,可以为今后高选择性镇痛药的研发及临床治疗提供思路.     

2000～2002年我院阿片类止痛药应用及消耗分析

阿片类止痛药又称强效中枢性镇痛药,是通过与体内阿片受体结合而产生镇痛效应的一类药物,可用于外科手术、外伤及内科疾病的镇痛和镇咳,它已成为控制晚期癌症疼痛,术中止痛最有效的药物之一.本人通过对我院2000～2002年阿片类止痛药的应用、消耗情况分析,了解阿片类止痛药在我院的应用情况,为合理应用阿片类止痛药提供参考.     

癌痛住院患者阿片类药物合理使用分析

目的对我院住院的癌痛患者治疗进行调查分析,为临床合理使用阿片类药物提供参考。方法检索我院2012年1月至12月癌痛住院患者的电子病历,对阿片类药物进行用药频度（DDDs）、药物利用指数（DUI）、癌痛分布、癌症患者出院疼痛评分和用药合理性进行评价。结果共计286例癌痛治疗患者,癌痛控制不佳有82例,占比28．7％;余204例疼痛强度≤3。阿片类长效制剂曲马多缓释片、芬太尼透皮贴剂、盐酸羟考酮缓释片、吗啡缓释片分别为DDDs前4位,在各型癌痛治疗中占主导地位。部分科室不合理使用哌替啶注射剂比例较高。结论阿片类药物的使用基本合理,还应更严格按照癌症疼痛诊疗规范使用阿片类药物,癌痛规范化治疗示范病房的创建还需要进一步深化。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.