Drug interactions with new oral anticoagulants in elderly patients

Introduction: This review attempts to summarise what is known about Drug-drug interactions (DDIs) of the new oral anticoagulants (NOACs) in elderly patients. The literature was searched for: ‘CYP3A4’, ‘CYP2C9’, ‘P-glycoprotein’, ‘acetylsalicylic-acid’, ‘non-steroidal anti-inflammatory’, ‘clopidogrel’, ‘ticagrelor’, ‘prasugrel’ and ‘dabigatran’, ‘rivaroxaban’, ‘edoxaban’, or ‘apixaban’. ‘Elderly’ was defined as ≥75 years.

Areas covered: Publications about DDIs of NOACs were found for 35% of 140 potentially interacting drugs. Reports about DDIs of cardiovascular drugs, were most frequent, followed by anti-infective and nervous system drugs. Reports about elderly were found for only 47 patients. DDIs were reported most frequently in association with dabigatran. Dabigatran is the only NOAC interacting with proton-pump-inhibitors.

Expert commentary: Dabigatran was the first NOAC approved, so it is not possible to determine whether the higher number of reports about DDIs with dabigatran compared with other NOACs is due to a higher rate of DDIs or to the length of time during which this drug has been in use. Most of the data is derived from subgroup-analyses of trials, sponsored by NOAC manufacturers, consequently there is a lack of independent data. Because of the scarcity of data, the clinical relevance of DDIs of NOACs is uncertain at present, especially in elderly patients.     

5’（S）-1，1-亚乙二氧基-5-氧代-（5’-乙基-5’-羟基-2’H,5’H，6＇H-6-氧代吡喃）-[3’-4’-f]-△^6（8）-四氢中氮茚的合成研究

目的合成20（S）-喜树碱类抗肿瘤药物关键中间体5’（S）-1，1-亚乙二氧基-5-氧代-（5’-乙基-5，-羟基-2’H，5＇H，6＇H-6-氧代吡喃）-[3’，4＇-f]-△^6（8）-四氢中氮茚。方法以1，1-亚乙二氧基-5-氧代-（5’-乙基-2’H，5＇H，6＇H-6-氧代吡喃）-[3’，4＂-f]-△^6（8）-四氢中氮茚为原料，经碘催化氧化、动力学拆分、碱水解3步得到光学纯目标化合物。结果与结论该合成路线操作简单，总收率15．7％，ee值96％。     

Worries about others’ substance use—Differences between alcohol,cigarettes and illegal drugs?

BackgroundWhile it is well documented that many experience harm from others’ substance use, little is known about the psychological strain associated with others’ use. The aims were: (1) to describe the prevalence of worries about others’ alcohol, cigarette and illegal drug use, (2) whose substance use people worry about, (3) the overlap in worries, and (4) to examine how worries about others’ use of each substance vary according to demographics, own substance use and experience of harm from others’ use.MethodsA population survey was conducted among 16–64 year old Norwegians (N = 1667). Respondents’ reported on worries about others’ alcohol, cigarette and illegal drug use, measures of experiences of harm from others’ use of the three substances, and own substance use.ResultsWorries about others’ drinking were most prevalent. Among those who worried, others’ cigarette and illegal drug use caused more frequent worry. While worry about cigarette use was mostly associated with family members’ use, worry about others’ alcohol and illegal drug use more often concerned friends’/acquaintances’ use. About half worried about others’ use of at least one substance. Across all three substances, experience of harm from others’ substance use was most strongly related to worries.ConclusionWorries about others’ substance use are common and reflect the prevalence of use of the substances in the population. In sum, the findings suggest that worry about others’ alcohol and illegal drug use is primarily related to acute harm while worry about others’ cigarette smoking is more related to chronic harm.     

Pleasure and excess: Using Georges Bataille to locate an absent pleasure of consumption

This article will engage with some recent changes in addiction discourses and research in order to introduce a new version of pleasure. Looking at how addiction research has reframed the ‘addict’ as a socially situated and contingent ‘consumer’, I will try to understand the role of excess in the distinction between ‘normal’ and ‘problematic’ consumption. This distinction remains prevalent, even in recent works on pleasure and drug-use. Pleasure is crucial here, because it is intimately related to consumption, yet has been previously ignored in research. Whereas the previous distinguishing feature of ‘addict’ and ‘non-addict’ can be argued to have been one of ‘production’ and ‘consumption’ (alongside a whole list of other attributes), the current debate seems to focus on various forms of consumption – the pursuit of pleasure through consumption being contentious. I argue that Bataille's formulation of overwhelming pleasure offers a way of combining excess and pleasure in a manner that is not problematic, further breaking down the distinction between ‘normal’ and ‘abnormal’ consumption. However, at the same time a new dichotomy is created between ‘overwhelming’ and ‘purposive’ pleasure, a distinction that might offer new ways of distinguishing ‘problematic’ and ‘unproblematic’ consumption in relation to drug-use. The version of pleasure formulated is argued to be absent in current work looking at pleasure in addiction, and a valuable addition to the growing repertoire of the types of pleasure available to addiction research.     

ASA404: update on drug development

Background: Interrupting tumour blood flow and delivery of nutrients to cause tumour death is the aim of antiangiogenic and vascular disrupting agents (VDAs). ASA404 is the first VDA to enter Phase III trials. Objective: We review the preclinical and clinical data on this interesting agent and consider its place in modern therapeutics. Methods: PubMed database was searched for ‘ASA404’, ‘AS1404’, ‘DMXAA’, ‘vascular disrupting agents’, ‘ASA404 clinical trials’, ‘AS1404 clinical trials’, ‘DMXAA clinical trials’. Results/conclusions: ASA404 is a tumour VDA that is well tolerated and has shown promise in the treatment of NSCLC in combination with paclitaxel and carboplatin. A confirmatory Phase III trial is currently ongoing.     

重视H型高血压 预防脑卒中发生

H型高血压在我国高血压患者中比例高,且是卒中发生的独立危险因素。认识、控制及管理H型高血压是预防脑卒中发生的有效措施之一。本文介绍H型高血压的发病率、病因、发病机制,重点讨论其生活方式管理、药物治疗,并对控制H型高血压、预防脑卒中的发生进行展望。     

Making medicine; producing pleasure: A critical examination of medicinal cannabis policy and law in Victoria,Australia

Several jurisdictions around the world have introduced policies and laws allowing for the legal use of cannabis for therapeutic purposes. However, there has been little critical discussion of how the object of ‘medicinal cannabis’ is enacted in policy and practice. Informed by Carol Bacchi’s poststructuralist approach to policy analysis and the work of science and technology studies scholars, this paper seeks to problematise the object of ‘medicinal cannabis’ and examine how it is constituted through governing practices. In particular, we consider how the making of the object of ‘medicinal cannabis’ might constrain or enact discourses of pleasure. As a case example, we take the Victorian Law Reform Commission’s review of law reform options to allow people in the Australian state of Victoria to be treated with medicinal cannabis. Through analysis of this case example, we find that although ‘medicinal cannabis’ is constituted as a thoroughly medical object, it is also constituted as unique. We argue that medicinal cannabis is enacted in part through the production of another object (so-called ‘recreational cannabis’) and the social and political meanings attached to both. Although both ‘substances’ are constituted as distinct, ‘medicinal cannabis’ relies on the ‘absent presence’ of ‘recreational cannabis’ to define and shape what it is. However, we find that contained within this rendering of ‘medicinal cannabis’ are complex enactments of health and wellbeing, which open up discourses of pleasure. ‘Medicinal cannabis’ appears to challenge the idea that the effects of ‘medicine’ cannot be understood in terms of pleasure. As such, the making of ‘medicinal cannabis’ as a medical object, and its invocation of broad notions of health and wellbeing, expand the ways in which drug effects can be acknowledged, including pleasurable and desirable effects, helping us to think differently about both medicine and other forms of drug use.     

龙血竭中黄烷和高异黄烷类化学成分研究

目的研究龙血竭二氯甲烷提取部位中黄烷和高异黄烷类成分。方法利用硅胶、聚酰胺柱色谱及反复重结晶等方法进行分离纯化,根据理化性质和波谱分析对分离得到的化合物进行结构鉴定。结果分离得到6个化合物,分别鉴定为7-羟基-4′-甲氧基黄烷(1)、4′-羟基-7-甲氧基-8-甲基黄烷(2)、5,4′-二羟基-7-甲氧基-6-甲基黄烷(3)、7,4′-二羟基高异黄烷(4)、6,4′-二羟基-7-甲氧基高异黄烷(5)和10-羟基-11-甲氧基龙血酮(6)。结论化合物6为首次从剑叶龙血树中分离得到,化合物2为首次从龙血竭中分离得到。     

药学服务中药师情商的培养

目的提高药学服务中药师的情商。方法分析情商在药学服务中的作用,探讨提高药师情商的方法。结果与结论自我情绪的控制、感知和调节患者的情绪,是药师必备的情商。对药师进行药学服务理论的教育和药学服务实践的培训,是提高药师情商的基本要素。     

Studies in the Natural History of Cocaine Use-Theoretical Afterword

A central commonality between the studies reported in this edition is argued to be important. They reveal a globalized pattern of cocaine use among geographically diverse groups of young, urban, secular people. Cocaine is used for recreational and entertainment purposes, is not commonly associated with ‘drug problems’ and is part of a ‘lifestyle’ in which the ‘rhythms’ of that lifestyle dictate cocaine use, not vice versa. Three general arguments are advanced in relation to this finding. First, the pattern of controlled use with few problems is surprising only to those who operate with defective models of human agency. Second, the rhythms of life are historically varied- some of the ‘rhythms’ of modernity and postmodernity are peculiarly fitted to drug use. Third, even within a given epoch, rhythms are varied between different social locations, creating different ‘settings’ for drug use and hence possibly different use patterns for (chemically) the ‘same drug’.     

Drugs,the democratic civilising process and the consumer society

The present article addresses the question of why drug use became an important phenomenon in the Western world and remained so. Even in scientific literature drug use is most often treated as ‘problematic’ behaviour. On the contrary, the present article argues that existing sociological models that have been used to grasp other cultural pursuits that are accepted as ‘normal’ and not as intrinsically ‘problematic’ can be fruitfully applied to understanding drug use. Two concepts will be discussed, namely that of Norbert Elias’ of the ‘civilising process’ and that of the ‘consumer society’. Firstly, the direction of the ‘civilising process’ has during the 20th century been for a part reversed. Though within boundaries set by continuing self-control, the body and the affects are readmitted into the public sphere. Drug use is part of this ambivalent phenomenon of ‘controlled de-control’. Secondly, the attractiveness of drugs expresses general preferences of the consumer society for the ‘wasteful’ and the ‘dream-like’; qualities which drugs epitomise in the most pronounced way.     

The debate over dopamine’s role in reward: the case for incentive salience

Introduction

Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: ‘liking’, learning, and ‘wanting’. Does dopamine mostly mediate the hedonic impact of reward (‘liking’)? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli (‘wanting’)? Each hypothesis is evaluated here, and it is suggested that the incentive salience or ‘wanting’ hypothesis of dopamine function may be consistent with more evidence than either learning or ‘liking’. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic ‘liking’ for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal ‘wanting’, and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive ‘wanting’ in addiction, but also provides opportunities for experiments to disentangle ‘wanting’, ‘liking’, and learning hypotheses. Results from studies that exploited those opportunities are described here.

Conclusion

In short, dopamine’s contribution appears to be chiefly to cause ‘wanting’ for hedonic rewards, more than ‘liking’ or learning for those rewards.     

阿糖胞苷5’-缬氨酸酯前体药物的小肠吸收机制

目的 研究阿糖胞苷的5’-缬氨酸酯前药在大鼠小肠内的吸收情况。方法 运用单向灌流模型研究药物在小肠内的吸收机制，利用高效液相色谱法测定药物和酚红在灌流液中的浓度。结果 阿糖胞苷 5’-缬氨酸酯前药的小肠渗透率是母药阿糖胞苷的10.6倍，在小肠内的吸收存在浓度依赖性，能够被小肠寡肽转运蛋白的专属底物头孢氨苄明显抑制。结论 阿糖胞苷 5’-缬氨酸酯前药是小肠寡肽转运蛋白的底物，在大鼠小肠内的吸收是由小肠寡肽转运蛋白介导的主动转运过程。     

Academic analysis of the Institute of Medicine report: The Future of Drug Safety

This paper analyzes the influential September 2006 Institute of Medicine (IOM) report entitled The Future of Drug Safety. It also analyzes the US FDA’s and the politicians’ FDA Amendments Act (FDAAA) response to it from a risk-communication perspective. This article begins with an extensive background discussion as to why the IOM report was commissioned. Then, it outlines and analyzes, from a risk-communication perspective, a number of the IOM’s suggested recommendations. In the third section, a number of overarching critiques of the IOM report are provided and, in the final section, a similar analysis is provided for the FDA’s and politicians’ (FDAAA) responses to the IOM report. Overall, the IOM’s report is an intelligent, well-structured document that provides a number of very useful recommendations. That said, the report is comparatively weak with regard to its recommendations associated with risk communication. Medical and drug risk communication is currently in its infancy.     

肝肾囊肿硬化疗法的改良

目的　对Bean肝肾囊肿治疗方法加以改良 ,并比较两种方法的临床疗效。方法　采用Bean法治疗 75例 ,改良法治疗 77例 ,改良法在Bean法基础上穿刺囊肿内插管 ,用 5 0 %葡萄糖代替无水酒精作硬化剂。结果　Bean法有 5 2例一次完成治疗 (6 9.33% ) ,随访治愈率 72 % ,有 43例治疗时出现中度以上疼痛 (5 3.33% )。改良法 76例一次完成治疗 (98.70 % ) ,治愈率 10 0 % ,病人无任何不适感及并发症。改良组一次治疗成功率和治愈率均显著高于Bean法 (P <0 .0 0 1)。结论　改良法明显优于Bean法。     

Drug Courts coming to Britain

This paper discusses research findings on non-biological risk factors associated with illicit drug use. There is an established body of North American research in this field, and a growing European literature. We find that there is an interplay of individual and environmental factors associated with drug use, with the permeation of their interactions potentially limitless. Within the behavioural science literature, we identify three main analytical dimensions for understanding ‘risk factors’. These are: ‘intrapersonal’; ‘micro-environmental’; and ‘macro-environmental’. We note that it is not new to emphasize drug use as a social activity, involving social interactions within particular social environments, but that, despite this, the balance of focus in research tends towards ‘extra-environmental’ or ‘individualistic’ interpretations. We emphasize that future research is best oriented towards generating data of practical value for the development of interventions rather than attempting to delineate causative factors. The failure of most risk factors research rests in its incapacity to capture the variety of social and environmental influences on drug use, and the relevance of these for developing socially appropriate interventions. In addition to recognizing the importance of targeting interventions towards ‘high risk’ populations and ‘high risk’ forms of drug use, we emphasize throughout the importance of the ‘risk environment’ in mediating patterns of drug use.     

Aripiprazole: pharmacology and evidence in bipolar disorder

Aripiprazole is a psychotropic agent with a novel pharmacologic profile. The purpose of this article is to review the pharmacology, efficacy and safety of aripiprazole in bipolar disorder. The authors conducted a PubMed search of all English-language articles published between January 1995 and February 2007. The key search term was ‘aripiprazole’ combined with: ‘randomized controlled trial’, ‘pharmacology’, ‘pharmacokinetics’, ‘pharmacodynamics’, ‘depression’, ‘mania’, ‘maintenance’ and ‘bipolar disorder’. Abstracts and proceedings from national and international psychiatric meetings were also reviewed. The search was augmented with a manual review of relevant article reference lists. This review is limited to pivotal registration, as well as acute and maintenance, randomized controlled trials in bipolar disorder. Aripiprazole is established as efficacious in acute mania and in the maintenance treatment of bipolar disorder. Aripiprazole has a favorable safety and tolerability profile, with minimal propensity for clinically significant weight gain and metabolic disruption. Extrapyramidal side effects, such as akathisia, are reported and may be treatment limiting in some cases. The hazard risk for tardive dyskinesia in the bipolar population is unknown. Aripiprazole constitutes an alternative mood-stabilizing pharmacologic avenue in bipolar disorder; its comparative efficacy in long-term recurrence prevention and bipolar depression is a future research vista.     

“What constitutes a ‘problem’?” Producing ‘alcohol problems’ through online counselling encounters

Typically, health policy, practice and research views alcohol and other drug (AOD) ‘problems’ as objective things waiting to be detected, diagnosed and treated. However, this approach to policy development and treatment downplays the role of clinical practices, tools, discourses, and systems in shaping how AOD use is constituted as a ‘problem’. For instance, people might present to AOD treatment with multiple psycho-social concerns, but usually only a singular AOD-associated ‘problem’ is considered serviceable. As the assumed nature of ‘the serviceable problem’ influences what treatment responses people receive, and how they may come to be enacted as ‘addicted’ or ‘normal’ subjects, it is important to subject clinical practices of problem formulation to critical analysis. Given that the reach of AOD treatment has expanded via the online medium, in this article we examine how ‘problems’ are produced in online alcohol counselling encounters involving people aged 55 and over. Drawing on poststructural approaches to problematisation, we not only trace how and what ‘problems’ are produced, but also what effects these give rise to. We discuss three approaches to problem formulation: (1) Addiction discourses at work; (2) Moving between concerns and alcohol ‘problems’; (3) Making ‘problems’ complex and multiple. On the basis of this analysis, we argue that online AOD counselling does not just respond to pre-existing ‘AOD problems’. Rather, through the social and clinical practices of formulation at work in clinical encounters, online counselling also produces them. Thus, given a different set of circumstances, practices and relations, ‘problems’ might be defined or emerge differently—perhaps not as ‘problems’ at all or perhaps as different kinds of concerns. We conclude by highlighting the need for a critical reflexivity in AOD treatment and policy in order to open up possibilities for different ways of engaging with, and responding to, people’s needs in their complexity.     

‘Never drop without your significant other,cause that way lies ruin’: The boundary work of couples who use MDMA together

MDMA has a variety of pro-social effects, such as increased friendliness and heightened empathy, yet there is a distinct lack of research examining how these effects might intertwine with a romantic relationship. This article seeks to compensate for this absence and explore heterosexual couples’ use of MDMA through the lens of the boundaries they construct around these experiences. Three couple interviews, two diary interviews and eight written diaries about couples’ MDMA practices were analysed. Douglas’ (2001) and Stenner’s (2013) work around order, disorder and what lies at the threshold between the two are employed here. This conceptual approach allows us to see what happens at the border of MDMA experiences as crucial to their constitution. Two main themes are identified in the data. First, MDMA use was boundaried from daily life both temporally and corporeally: the drug was tied to particular times in people’s lives as well as the performance of rituals which engaged the material world and reenchanted everyday spaces and selves. Secondly, other people are excluded from MDMA experiences to varying degrees in order to preserve the emotionally intense space for the couple alone. This paper claims that MDMA use forms part of a spectrum of relationship ‘work’ practices; a unique kind of ‘date night’ that revitalises couples’ connection. Hence, MDMA should be recognised as transforming couple as well as individual practices. Finally, it is suggested that harm reduction initiatives could distinguish more ‘messy’ forms of emotional harm and engage with users’ language of ‘specialness’ to limit negative impacts of MDMA use.