医源性阿片类药物戒断在儿童ICU中的评估研究

目的 对儿童ICU阿片类药物的戒断症状进行评估探索。方法 对连续5 d及5 d以上接受阿片类药物的儿童ICU患儿进行停药后的索菲亚戒断症状量表（Sophia observation withdrawal symptoms scale,SOS）回顾性评分。结果 共86例患儿,年龄中位数为7个月（四分位距5~12月）,研究样本的戒断症状发生率为22%,总疗程中位数9 d（四分位距为6.25~12 d）,SOS ≥ 4患儿的疗程中位数为7 d（四分位距为6~9 d）,骤停易导致戒断症状发生,评估中出现频率最高的症状依次是发烧、呼吸急促、躁动、腹泻、痛哭流泪。结论 儿童ICU患儿存在潜在医源性阿片类药物戒断风险,应重视阿片类药物戒断症状的识别与评估,最大程度地避免戒断症状的发生。     

阿片药物戒断的生化机制

19世纪80年代人们就认识到医用阿片类药物可致身体依赖性和精神依赖性。之后．阿片药物戒断症引起科学家和社会学家的极大关注，他们不仅从精神上和道义上阐述阿片戒断的机理，而且用愈益明确的生化理论解释停止用药后出现的自主功能紊乱和精神烦恼等症状。阿片药物依赖性的问题，虽然主要涉及用药患者，但由于劳动能力的丧失、治疗费用和为提供及获得药物的大量犯罪给社会带来沉重负担，     

阿片类药物依赖者脱毒治疗的临床检查

脱毒治疗(detoxification)指被滥用毒品从依赖个体中逐渐清除的过程.脱毒治疗的概念包含下面几层含义:治疗过程是一个逐渐清除体内毒品,减轻主观难受,减少可观察或可测量的戒断症状,预防突然中止毒品后产生的健康风险.本文主要介绍阿片类药物依赖脱毒治疗的临床检查.     

电压依赖性钙通道与阿片类药物成瘾之间的关系

阿片类药物成瘾属慢性复发性脑病,主要表现为对成瘾性药物的强迫用药行为及用药量的不可控制性,其机制复杂,治疗困难,复发率高,因此对阿片类药物依赖戒断的机制及治疗的研究一直是医学界关注的热点和难点.大量研究证明电压依赖性钙通道（voltage dependent calcium channels,VDCCs）与阿片类药物成瘾的形成之间存在着密切的关系,VDCCs可通过多种途径参与阿片成瘾的形成.并且临床上,多种钙拮抗剂治疗吗啡戒断综合征也取得了一定的疗效,间接证明了VDCCs与阿片成瘾的形成之间存在着密切的关系.现对VDCCs与阿片类药物成瘾之间的关系综述如下.     

美国阿片戒断的药物治疗现状

2003年，美国有370万人终生用过海洛因，其中31．4万人既往用过海洛因，16．9万人既往某时点患海洛因依赖，这个数字可能被低估，因为社区的海洛因依赖率难以统计。美国毒品控制政策办公室（ONDCP）估计，美国有75-100万人患海洛因依赖^[1]。     

阿片类药物依赖戒断原理的研究进展

阿片类药物依赖戒断原理的研究进展徐贵丽综述蒋家雄审校（成都军区昆明总医院昆明邮编６５００３２）对阿片类药物依赖戒断原理的探讨一直是医学界关注的热点，研究涉及神经，受体，细胞内信号系统，效应器等一系列复杂的微观控系统。现简述近年来的一些进展。一、依赖戒...     

肾阳虚损与阿片类药物依赖戒断症状的关系

中医发展历史表明，对疾病本质的不断认识和深化是中医临床治疗水平提高的内在动力。因此在进行中医中药治疗药物依赖的过程中，只有加强对本病病因病机及病证演化规律的研究，才能找出不同时期、不同阶段的病证特点，形成具有中医治病特色的辨证论治的理论体系，使中医中...     

阿片类药物依赖建模和戒断症状评价方法研究进展

<正>药物成瘾是一种慢性、复发性脑疾病,行为学特征表现为强迫性用药。药物成瘾包括心理性依赖和生理性依赖,心理性依赖是病人对药物的强烈渴求;生理性依赖(也称为躯体性依赖)是重复多次滥用药物,造成中枢神经等全身多系统发生生理、生化、     

阿片类药物依赖的治疗学进展

介绍阿片类物质依赖的主要药物治疗学进展，主要包括三个步骤，重点介绍阿片受体激动药和非阿片受体激动药的使用，此外尚有非药物疗法及免疫疗法等。     

论中医药对阿片类药物成瘾者戒断及抗复吸整体序贯疗法

回顾、分析中医药对阿片类药物成瘾者戒断治疗研究现状及存在问题,借助现代生物医学对阿片类药物成瘾机理及戒断后生理变化过程的研究成果及分期概念,运用中医整体、辨证论治学说,论述戒断后辨期与辨证相结合的整体序贯治疗思路与方法,并进行临床示范研究,以期建立中医药戒毒及抗复吸诊疗的理论体系及系统治疗方案     

Use of methadone for prevention of opioid withdrawal in critically ill children

Background

Opioids are commonly administered to critically ill children for analgesia and sedation, but many patients experience opioid withdrawal upon discontinuation. The authors’ institution developed a protocol for using methadone to prevent opioid withdrawal in children who have received morphine by continuous IV infusion for 5 days or longer in the pediatric intensive care unit (PICU).

Objectives

The primary objectives were to determine if opioids were tapered according to the protocol and to determine the conversion ratio for IV morphine to oral methadone that was used. Secondary objectives were to describe the methadone dosage used and the clinical outcomes, to evaluate adjustments to methadone dosing, and to report the incidence of adverse effects.

Methods

A retrospective analysis of charts was conducted for pediatric patients who had received morphine by continuous IV infusion for 5 days or longer followed by methadone in the PICU between May 2008 and August 2009. Validated scoring systems (the Withdrawal Assessment Tool and the State Behavioral Scale) were used to assess symptoms of withdrawal and degree of sedation, respectively.

Results

Forty-three patients were included in the study, with median age of 8 months (range 0.25–201 months). For 31 patients (72%), the protocol was not used, and there were no patients for whom the protocol was followed to completion. The median duration of weaning was 10 days (range 0–91 days). The conversion ratio for IV morphine to oral methadone was 1:0.78 for anticipated 5-day weaning and 1:0.98 for anticipated 10-day weaning. During the first 10 days of weaning, 18 patients (42%) experienced withdrawal symptoms. The methadone dose was increased for 11 (26%) of the 43 patients. Patients were sedated for a median of 1 day (range 0–9 days), were comfortable for a median of 6.5 days (range 1–64 days), and were agitated for a median of 2.5 days (range 0–23 days). Naloxone was required for 2 patients.

Conclusions

The institution’s methadone protocol was not followed consistently during the study period, and practices for transitioning from morphine by continuous IV infusion to methadone with tapering were also inconsistent. Further studies are needed to determine the optimal conversion ratio for morphine to methadone and the optimal tapering regimen to minimize withdrawal symptoms and adverse events.     

Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction

A large range of neuroadaptations develop in response to chronic opioid exposure and these are thought to be more or less critical for expression of the major features of opioid addiction: tolerance, withdrawal and processes that may contribute to compulsive use and relapse. This review considers these adaptations at different levels of organization in the nervous system including tolerance at the mu-opioid receptor itself, cellular tolerance and withdrawal in opioid-sensitive neurons, systems tolerance and withdrawal in opioid-sensitive nerve networks, as well as synaptic plasticity in opioid sensitive nerve networks. Receptor tolerance appears to involve enhancement of mechanisms of receptor regulation, including desensitization and internalization. Adaptations causing cellular tolerance are more complex but several important processes have been identified including upregulation of cAMP/PKA and cAMP response element-binding signalling and perhaps the mitogen activated PK cascades in opioid sensitive neurons that might not only influence tolerance and withdrawal but also synaptic plasticity during cycles of intoxication and withdrawal. The potential complexity of network, or systems adaptations that interact with opioid-sensitive neurons is great but some candidate neuropeptide systems that interact with mu-opioid sensitive neurons may play a role in tolerance and withdrawal, as might activation of glial signalling. Implication of synaptic forms of learning such as long term potentiation and long term depression in opioid addiction is still in its infancy but this ultimately has the potential to identify specific synapses that contribute to compulsive use and relapse.     

药物支架的研究进展

本文回顾了药物支架的发展历史,讲述了现今药物支架的特点,并预测了药物支架的发展方向。文章从药物支架的结构入手,比较了临床上应用的主要几种药物支架。随着药物支架的不断发展,介入心脏病学会迎来更多的革命,药物支架取代裸支架是一种必然,可降解支架是新的里程碑。在未来,药物支架将主导整个冠心病介入治疗。     

Chronic pain management issues in the primary care setting and the utility of long-acting opioids

Importance of the field: Chronic/persistent pain – a highly prevalent condition that places a substantial burden on patients in terms of personal suffering, reduced productivity and health care costs – remains inadequately treated in many patients. The purpose of this review is to provide an overview and evaluate the burden and undertreatment of chronic/persistent pain, considerations for choosing an analgesic and the utility of long-acting opioids.

Areas covered in this review: A PubMed search was conducted to identify randomized, placebo-controlled trials evaluating the efficacy and safety of long-acting opioids in chronic pain conditions. The following search terms were used: long-acting opioids, extended-release opioids, controlled-release opioids, sustained-release opioids, and transdermal opioids. The search was limited to randomized, controlled trials published within the last 10 years (1998 – 2008). Studies meeting the following criteria were excluded from review: those focused on a neuropathic pain condition or specific patient subpopulations (e.g., opioid-experienced patients); those conducted outside the USA; and those evaluating a long-acting opioid that is not on the US market at present.

What the reader will gain: The reader will first develop a better understanding of the individual and societal ramifications of undertreated chronic pain. Then, a critical review of safety and efficacy data from well-controlled randomized studies will help readers understand the choices and variables that should be considered when selecting appropriate treatments for patients with chronic pain.

Take home message: Successful management of chronic/persistent pain should be individually tailored to each patient, taking into account his or her pain intensity and duration, disease state, tolerance of adverse events and risk of medication abuse or diversion. The literature supports the efficacy and safety of a number of long-acting opioids for the treatment of moderate to severe chronic pain, demonstrating sustained improvements in pain intensity and pain-related sleep disturbances with these agents.     

弱阿片药物与低剂量强阿片药物治疗中度癌痛的Meta分析与GRADE评价

目的：评价弱阿片类药物（Weak Opioids,WO）与低剂量强阿片类药物（Low-Dose Strong Opioids,LDSO）治疗中度癌痛的有效性和安全性。方法：以"吗啡","羟考酮","曲马多","可待因","中度癌痛"为关键词对Pubmed、EMbase、Cochrane Library、中国知网、万方、维普等数据库进行检索。以临床疗效为主要结局、毒副反应（恶心呕吐,嗜睡,厌食和便秘）为次要结局,采用软件Review Manager 5.3对数据进行处理,并采用软件GRADE profiler 3.6对结果证据质量进行评级。结果：纳入4项随机对照研究,共计708例患者。结果表明LDSO对中度癌痛的控制要优于WO[OR=3.50,95% CI（2.39 to 5.13）,P<0.000 01]。而在毒副反应方面,两组的恶心呕吐[OR=0.92,95% CI（0.59 to 1.42）,P=0.69]、嗜睡[OR=1.23,95% CI（0.74 to 2.05）,P=0.42]、厌食[OR=1.19,95% CI（0.59 to 2.37）,P=0.63] 以及便秘[OR=1.34,95% CI（0.87 to 2.07）,P=0.19] 均无显著性差异。缓解率和各毒副反应的GRADE证据评价级均为中级。结论：在治疗中度癌痛中,LDSO的疗效优于WO,且耐受性良好,提示临床可以采用弱化二阶梯方案,将LDSO用于治疗中度癌痛。     

Bioresorbable drug-eluting scaffolds for treatment of vascular disease

ABSTRACT

Introduction: Theoretical advantages of fully bioresorbable scaffold (BRS) stem from transient vessel support without rigid caging. Therefore, it could reduce long-term adverse events associated with the presence of foreign materials.

Areas covered: This article will provide an overview of: drug-eluting BRS for various applications in the treatment of vascular disease; The mechanisms of active agent release from such scaffolds; currently available drug-eluting BRS and their future applications are also discussed.

Expert opinion: The current BRS have been developed in order to achieve optimal vascular patency while providing long-term safety. The clinical efficacy and safety of BRS in coronary treatment have been reported as equal to that of the current metallic drug eluting stents in simple lesions. The application of BRS can potentially be expanded to other vascular beds. The research in bioengineering for the appropriate materials should not only focus on biocompatibility but also should be tailored according to the sites of implantation, which may require different strength and supporting period. The ultimate goal in this field is to develop a biocompatible device that provides equivalent and complementary therapy to other devices, and is able to disappear when the mechanical support and drug delivery are no longer required.     

Action of chlormethiazole in a model of ethanol withdrawal

Mice withdrawn from exposure for 14 days to ethanol inhalation showed the expected signs of ethanol withdrawal including convulsive behaviour. Injection of chlormethiazole (100 mg/kg) 5 h after the start of withdrawal, at the time that the convulsive behaviour was near maximal, resulted in the virtual disappearance of the withdrawal — induced behaviour within 30 min, with its reappearance by 60 min. A dose of chlormethiazole of 40 mg/kg was without effect. The time course of the effect of chlormethiazole (100 mg/kg) in the withdrawal test was similar to its effect in raising seizure threshold and decreasing locomotor activity. Chlormethiazole did not alter in vitro binding of [³H]-PN 200-110 to the dihydropyridine sensitive Ca²⁺ channel. Chlormethiazole, a drug used clinically to treat ethanol withdrawal, has therefore been shown to be effective in this animal model of withdrawal. Dihydropyridine calcium antagonists are also active in the model but chlormethiazole is likely to work by a different mechanism and it is suggested that this may be by increasing GABAergic function.     

药物洗脱支架时代再狭窄的预防和治疗

药物洗脱支架有效地降低了再狭窄的发生率,扩大了冠脉介入治疗的领域。然而,随着介入治疗的病变越来越复杂,病例越来越多,其本身的再狭窄问题也变得令人瞩目。如何处理药物洗脱支架后的支架内再狭窄,已经成为心脏病学面临的新挑战。本文就药物洗脱支架再狭窄的原因、特点、预测因素、治疗策略作一综述。