丹参注射剂561例临床不良反应/事件分析

摘 要 目的：分析丹参注射剂所致不良反应发生的特点,为临床安全用药提供参考。方法：采用回顾性研究方法,对2012～2014年湖北省药品不良反应监测中心收集的561例丹参注射剂所致不良反应/事件（ADR/ADE）,以患者性别、年龄、过敏史,ADR/ADE发生时间、临床表现及转归等指标作为考查项,进行统计分析。结果：561例ADR/ADE患者男女比例为1∶1.109,主要发生人群为40岁以上的患者（85.93%）。共发生ADR/ADE 784例次,主要发生时间为给药后30 min以内（56.86%）,主要临床表现为皮肤及其附件损害（34.31%）、全身性损害（16.45%）、心率及心律紊乱（12.76%）,其中严重不良反应构成比为4.5%。结论：丹参注射液可引起不同程度的不良反应,临床用药时应给予足够重视,需加强ADR/ADE监测,提高用药安全性。     

972例阿片类药物不良反应/事件的回顾性研究

摘 要 目的：研究阿片类药物所致不良反应/事件（ADR/ADE）发生的特点,为临床安全用药提供参考。方法：采用回顾性研究方法,对2007年1月～2018年6月湖北省药品（医疗器械）不良反应监测中心收集的972例阿片类药物所致ADR/ADE,从患者性别、年龄、ADR/ADE发生时间、给药途径、临床表现及转归等方面进行统计分析。结果：972例ADR/ADE报告的患者男女比例为1 ∶1.20;51～70岁患者构成比较高;ADR/ADE主要发生在用药后24 h以内（66.46%）;主要临床表现为胃肠系统损害（38.96%）、中枢及外周神经系统损害（21.87%）、皮肤及其附件损害（10.46%）、全身性损害（9.23%）、呼吸系统损害（4.51%）,其中严重ADR/ADE构成比为10.49%。阿片类药物所致ADR/ADE的给药途径以静脉注射（34.57%）和口服给药（32.51%）为主。结论：阿片类药物可引起严重ADR/ADE,临床用药时需加强监测,提高用药安全性。     

某三甲医院2013～2017年219例新的和严重的药品不良反应报告分析

摘 要 目的：了解新的和严重的药品不良反应(ADR)发生的规律及特点。方法：收集某三甲医院2013～2017年上报的219例新的和严重的ADR报告,从患者性别、年龄,涉及药品种类、剂型,ADR累及器官/系统及主要临床表现、关联性评价、转归等方面进行统计分析。结果：219例ADR中,新的ADR 191例,严重的ADR 20例,新的严重的ADR 8例。关联性评价结果：1.83%为肯定,75.34%为很可能,22.83%为可能。ADR患者男女比例为0.84 ∶〖KG-*2〗1,50～80岁所占比例为61.19%。药物剂型以口服药为主,占57.99%,而严重的ADR涉及药品以注射剂为主。引起新的ADR的药品以中成药（含中药注射剂）为主,共60例（31.41%);引起严重的ADR的药品以抗微生物药物为主,共9例(32.14%)。严重的ADR主要临床表现为循环系统反应(39.29%),以过敏性休克为主。95.89%的患者发生ADR后痊愈或好转。结论：应注重对于50～80岁人群进行ADR监测,并加强中成药（含中药注射剂）、抗微生物药物和抗肿瘤药物尤其是奥沙利铂的监测力度。     

某三级甲等医院400例新的及严重的药品不良反应分析

摘 要 目的：了解某三级甲等医院药品不良反应（ADR）发生的特点,为临床安全用药、减少ADR发生提供参考。方法: 对2014～2016年收集上报的新的及严重的ADR从报告类型、年龄、性别、给药途径、药品种类、累及系统 器官方面进行分析。结果:新的及严重的ADR报告共有400例,占报告总数的64.52%;60～74岁患者所占比例最大,为34.25%;发生ADR的男女比例基本相当,男性（50.25%）略高于女性（49.75%）;静脉给药引起ADR例数最多（57.00%）;引起ADR的药品种类最多的为抗感染药物（31.25%）,其中头孢菌素类占比最多（32.00%）;主要累及系统 器官为皮肤及附件损害（33.00%）、胃肠系统损害（15.50%）及肝肾功能损害（14.00%）等。结论:全院应加强ADR监测与上报工作,从而规范药物使用,减少ADR的发生。     

157例新的/严重的药品不良反应报告分析

摘 要 目的:了解本院新的/严重的药品不良反应(ADR)的特点及规律,为临床安全用药提供依据。方法：收集本院2010年1月~2015年3月上报的新的/严重的药品不良反应报告,对患者年龄、性别、发生时间、给药途径、引起ADR的药品种类、ADR累及器官或系统及临床表现等方面进行统计分析。结果：新的/严重的ADR报告共157例,其中新的一般的ADR报告73例,严重的ADR报告60例,新的严重的ADR报告24例;ADR可发生于各年龄段,≥60岁比例较高（33.12%）;ADR多发生在用药后2 h内（73.88%）;给药途径以静脉静滴给药为主（82.17%）;涉及药品101种,以抗菌药（46.70%）所占比例最高,其次是中药制剂（14.37%）,引起ADR的前5位的药品均是抗菌药;ADR累及器官或系统及主要临床表现依次为全身性损害（28.06%）、皮肤及其附件损害（19.90%)、呼吸系统损害（15.82%）和中枢及外周神经系统损害（10.72%）。结论：新的/严重的ADR发生与多种因素有关,应提高新的/严重的ADR的监测水平,减少ADR风险。     

134例严重药品不良反应/事件报告分析

摘 要 目的：分析西安交通大学第一附属医院严重药品不良反应/事件(ADR/ADE)发生的原因及特点,为临床合理用药提供参考。方法：汇总统计该院2008～2015年134例严重药品不良反应/事件报告,分别从患者年龄、性别、药品种类、临床表现、给药途径及关联性评价等方面进行统计与分析。结果：发生严重ADR/ADE患者的男女比例为1.13∶1,老年人患者、涉及抗肿瘤药物和抗菌药物ADR/ADE的构成比分别为37.31%、37.31％和22.39％。报告例次最多的15个药品中,抗肿瘤药物8种,抗菌药物3种。静脉滴注发生ADR/ADE构成比85.4%。严重ADR/ADE的临床表现主要以全身性损害、血液系统损害和心血管损害多见。结论：重视抗肿瘤药物和抗菌药物ADR/ADE的监测,提高临床安全、有效、合理的用药水平,降低临床ADR/ADE风险,保障患者的用药安全。     

227例三唑类抗真菌药物不良反应报告分析

摘 要 目的：分析三唑类抗真菌药物不良反应（ADR）的发生的特点,为临床合理用药提供参考。方法：采用回顾性研究方法,对2012～2014 年湖北省药品不良反应监测中心数据库227例三唑类抗真菌药物ADR报告的患者年龄、性别,药物剂型、给药途径,ADR发生时间、累及器官系统分布及临床表现,ADR分级、关联性评价及其转归情况等进行统计分析。结果：三唑类抗真菌药物所致ADR患者男女比例为1∶1.32;各个年龄段均有分布,其中31～40岁年龄段构成比最高,占38.33%。ADR报告涉及9种药品剂型,以膏剂为主,占总剂型59.03%。ADR报告涉及给药途径主要包括外用（70.04%）和阴道给药（24.23%）等。所致ADR主要累及皮肤及其附件损害（69.87%）和女性生殖系统损害（24.02%）等,ADR临床表现为皮疹、瘙痒、恶心、呕吐、腹泻、腹痛等;其中咪康唑（42.73%）引起的ADR例数最多,酮康唑（36.56%）次之。227例ADR报告中一般的ADR 200例,新的ADR 27例。关联性评价结果：肯定17例,很可能68例,可能142例。ADR病例的转归以治愈和好转为主。结论：应严格控制药物的不合理使用,加强ADR监测,完善药物使用说明书,规范临床用药,以降低ADR/ADE风险。     

我院妇产科抗菌药物不良反应/事件相关因素分析

摘 要 目的:了解抗菌药品不良反应/事件（ADR/ADE）发生特点及相关因素,为安全用药提供依据。方法：回顾性分析2011～2013年我院妇产科上报的抗菌药物ADR/ADE报告。结果：165例ADR/ADE患者,平均年龄（28.76±6.80）岁,年龄越高,ADR/ADE发生率越高;青霉素类药物ADR/ADE发生率2.41%,居首位;头孢菌素类药物ADR/ADE例数占73.33%,但ADR/ADE发生率低于均值0.47%;超剂量使用与ADE发生有显著关系,超剂量使用头孢呋辛、头孢曲松发生ADE,P值分别为0.002,0.034;165例ADR/ADE患者,静脉滴注149例,肌内注射12例,口服4例。结论：加强抗菌药物处方审核和护理干预,加强ADR高发生率药物监测,严格控制输液量,以减少或避免ADR/ADE发生。     

由药品不良反应/事件看我院抗菌药物临床应用药物相关问题

摘 要 目的：对我院抗菌药物不良反应/事件（ADR/ADE）进行调查分析，探讨我院抗菌药物临床应用的药物相关问题(drug related problems，DRPs)，为我院抗菌药物的临床合理应用提供依据。方法：以我院2015年1月~2018年6月上报的242例抗菌药物相关ADR/ADE为研究对象，探讨其发生特点，同时采用DRPs分类法对抗菌药物使用的必要性、有效性、安全性进行评价研究。 结果：242例抗菌药物ADR/ADE病例中，女性多于男性，≥60岁患者占53.72%；共涉及9大类31个品种的药品，头孢菌素类构成比（47.93%）最高，左氧氟沙星和环丙沙星所致ADR/ADE病例最多，给药途径以静脉注射为主（94.63%）；严重ADR/ADE 22 例(9.09%)。涉及DRPs具体问题分类有DRP2、DRP3、DRP4、DRP5、DRP6，分别为5例、12例、5例、186例和34例。结论：应重视抗菌药物临床应用的DRPs，预防抗菌药物ADR/ADE的发生，促进抗菌药物安全合理应用。     

117例新的/严重的儿童药品不良反应分析

摘 要 目的：分析某院新的/严重的儿童药品不良反应（ADR）的特点,为促进儿童安全用药提供参考。 方法：对2017～2018年某院上报的新的/严重的儿童ADR报告进行回顾性分析,内容包括性别、年龄、既往ADR史、家族ADR史,ADR涉及药品品种、剂型及给药途径、是否超说明书用药,ADR累及的系统/器官、发生时间、对原患疾病的影响及转归、关联性评价等。 结果：2017～2018年某院上报117例新的/严重的儿童ADR,其中新的ADR 46例（39.32%）,严重的ADR 68例（58.12%）,新的严重的ADR 3例（2.56%）。关联性评价结果：肯定1例（0.85%）,很可能112例（95.73%）,可能4例（3.42%）。男性患儿78例（66.67%）,女性患儿39例（33.33%）;1～3岁患儿所占比例最高。药品剂型以注射剂（52.99%）为主;给药途径以静脉滴注（68.38%）为主。涉及药品品种14类58种,构成比最多的为抗感染药物（47.01%）;22例（18.80%）ADR存在超说明书用药。ADR累及系统/器官以皮肤及其附件系统（60.68%）为主,引起严重皮疹23例（19.66%）。用药后0～5 min内（41例）发生ADR比例最高。115例（98.29%）ADR对患儿原患疾病无明显影响,仅2例（1.71%）使患儿病程延长。 结论：儿童临床用药需加强监测,国家应尽快出台儿童安全用药的指南及相关法规,药品生产企业需积极完善补充药品说明书中儿童用药信息,临床药学人员应加强对医护及患儿家属安全用药知识的宣教,全面促进儿童安全用药。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.