基于药品说明书解析β-内酰胺类抗生素皮肤过敏试验

目的:解析β-内酰胺类抗生素皮肤过敏试验现状,提出可行的建议,以保证用药安全。方法:收集我院现供应的45种β-内酰胺类抗生素的药品说明书,采用Excel 2003对其中皮肤过敏试验的警示内容进行归纳分析;同时结合文献,解析β-内酰胺类抗生素的皮试现状。结果:45种β-内酰胺类抗生素的药品说明书中,只有注射用盐酸头孢替安明确列出皮肤敏感试验方法;明确建议用药前应皮试的有16种药物,占药品总数的35.56%,包括4种注射用头孢菌素类药物、9种注射用青霉素类药物和3种口服青霉素类药物。目前国内对β-内酰胺类抗生素的皮试问题仍存在争议,国家卫生行政部门无统一规定,国内各医院的皮试方法也不尽相同。结论:为减少用药隐患,建议在使用β-内酰胺类抗生素前应详细询问患者的过敏史,严格按药品说明书要求谨慎使用,注射给药前应皮试。口服青霉素类药物给药前也应进行皮试。     

湖北省内医疗机构β-内酰胺类抗菌药物皮肤试验现状调查分析

目的： 通过问卷调查分析湖北省内各家医院β-内酰胺类抗菌药物皮肤试验的实际情况。方法： 通过湖北省临床药学质量控制中心向湖北省内各市、州部省属医疗机构临床药学部门发出调查问卷,调查各医疗机构使用β-内酰胺类抗菌药物前的皮肤试验方法。结果： 收到反馈信息完整的问卷有849份（反馈率为91.09%）,其中二级及以上医院303家,基层卫生院及社区医院546家。调查显示各医疗机构在β-内酰胺类抗菌药物皮试品种、皮试方法、存在过敏史时药物的选择以及口服青霉素制剂是否进行皮试等方面均存在明显差异。结论： 本研究反映了湖北省内医疗机构在β-内酰胺类抗菌药物皮肤试验方面缺乏统一标准,卫生部门亟需尽快制定相关临床指南或操作实施规范,以保证临床使用β-内酰胺类抗菌药物的安全性与规范性。     

β内酰胺类抗生素的皮肤过敏试验现状及建议

目的 对目前我国β内酰胺类抗生素的皮肤过敏试验现状进行分析探讨.方法 通过对β内酰胺类抗牛素过敏机制原因的分析及国内皮肤过敏试验现状的了解,结合我国现行的管理措施,对该类药物临床是否应进行皮肤过敏试验提出建议.结果 和结论 β内酰胺类抗生素用药前,应仔细询问病史,有明确过敏史者禁用;青霉素类药物使用前,应进行皮肤过敏试验;头孢菌素类药物皮试可不作为常规,但对青霉素过敏者应用拟用药物进行皮试.     

基于药品说明书对β-内酰胺类抗生素皮肤过敏试验临床意义的探讨和建议

目的 通过探讨β-内酰胺类抗生素变态反应发生的机制和皮肤敏感试验(简称皮试)国内外现状,为临床安全合理应用β-内酰胺类抗生素提供参考。方法 收集我院现应用的44个品规β-内酰胺类抗生素的药品说明书,对其中的皮试警示内容进行归纳统计;同时查阅国内外文献和共识对当前的β-内酰胺类抗生素的皮试研究进展进行了解。结果 我院目前应用的β-内酰胺类抗生素44个品规的药品说明书中,明确要求用药前皮试的有青霉素类药物9个品规,头孢菌素类1个品规,占22.72%,建议皮试有口服青霉素类1个品规、注射用头孢菌素类3个品规,占9%,其余的青霉素类2个品规、头孢菌素类25个品规、碳青霉素类3个品规,共30个品规未注明皮试要求,占68.18%,明确列出皮试方法的仅有注射用青霉素钠1个品规;目前青霉素类的致敏机制非常清楚,和皮试方法有统一的行业规范和标准,而头孢菌素类的皮试必要性,多数研究结果认为无意义,而且缺乏相关的法律规范和统一的行业标准。结论 为降低使用β-内酰胺类抗生素过敏的风险,建议严格遵循药品说明书的要求和结合患者的过敏史等综合情况考虑是否进行皮试,全程严密观察并且做好防范救治措施。     

基于β-内酰胺类药物国内外皮试现状论政府层面出台皮试规范的迫切性

β-内酰胺类抗生素是儿科使用率最高的一类药物,过敏反应是该类药物最常见的一种不良反应,严重者可发生过敏性休克导致死亡。关于β-内酰胺类抗生素在使用前是否进行皮肤过敏试验（简称皮试）一直存有争议。根据我们对国内55家医院开展的β-内酰胺类抗生素皮试现状调查结果,结合国内外文献,分析了β-内酰胺类抗生素发生过敏反应的机制与原因、β-内酰胺类抗生素皮试的价值与意义、国内外β-内酰胺类抗生素皮试的现状及国内皮试存在的问题;认为青霉素皮试是目前预测青霉素I型过敏反应最快捷、敏感、经济的方法,头孢菌素类、碳青霉烯类、单环类从科学性、规范性、经济性等方面综合考虑,目前的循证依据并不支持进行皮试;β-内酰胺类抗生素在国内至今还未形成统一的皮试规范,包括皮试标准试剂、操作方法和皮试液浓度、剂量以及皮试结果的判定标准,临床在皮试操作和皮试结果的正确解读存在困惑,建议国家政府层面加强统一规范,重视β-内酰胺类抗生素过敏反应的救治措施,防止和减少药物不良反应,避免药品浪费和大量人力物力消耗以及废弃物造成的环境污染,更好地促进β-内酰胺类抗生素的合理应用。     

对β-内酰胺类抗生素皮试的几点建议

β—内酰胺类抗生素系指化学结构式中具有内酰胺环的一大类抗生素 ,包括青霉素类、头孢菌素类、头霉素类、单环内酰胺类及其他非典型 β—内酰胺类抗生素。此类抗生素以其抗菌活性强、毒性低、临床疗效好等优点而广泛地用于临床 ,但由其引发的过敏反应却严重影响着患者的安全 ,过敏试验的不规范亦困扰着医疗部门的方方面面 ,特别是口服制剂是否需要皮试看法更不一致。本文就此问题进行阐述 ,供大家商讨。1　青霉素类抗生素 (含青霉素复合制剂 ) :本类药物包括青霉素类和半合成青霉素临床应用青霉素类时 ,较多出现过敏反应 ,包括皮疹、药物热…     

2011～2013年武汉地区32家医院β-内酰胺复方制剂用药分析

摘 要 目的:了解抗菌药物专项整治活动期间武汉地区β-内酰胺复方制剂用药情况,为合理用药提供依据。方法：统计分析2011～2013年武汉地区32家医院β-内酰胺复方制剂的用药金额、用药频度和日均费用。结果：2011～2013年武汉地区32家医院β-内酰胺复方制剂的用药金额呈逐年增长趋势,特别是头孢菌素/酶抑制药的增长更为显著。三年中用药金额最高的药物是头孢哌酮/他唑巴坦,用药频度最高的是羟氨苄青霉素/克拉维酸钾。结论：通过抗菌药物专项整治活动,β-内酰胺复方制剂的品种、品规数得到控制,但用药量仍呈显著增长趋势。为了促进β-内酰胺复方制剂的合理应用,除了加强管理,还应充分发挥国家细菌耐药监测网的指导作用。     

β-内酰胺类抗生素皮肤过敏试验探讨

2005年版的《中华人民共和国药典临床用药须知》仅对青霉素类抗生素皮肤过敏试验(以下简称皮试)作了较为明确的规定,所有具有法律效应的规定对其他类β-内酰胺类抗生素使用前是否要做皮试及结果如何判定没有定论,药品说明书也存在标准不一的现象,这给实际工作带来了困难。β-内酰胺类抗生素是指分子中含有β-内酰胺环的抗生素,包括青霉素类、头孢菌素类、β-内酰胺酶抑制剂、氧头孢类、碳青霉烯类、单酰胺环类等,其品种繁多,剂型、规格各不相同,是临床最为常用的抗菌药物,过敏反应及过敏性休克发生率较高,为皮试的主要对象。由于各类药物的…     

β-内酰胺类抗菌药物皮试的国内现状调查

目的:了解国内医院β-内酰胺类抗菌药物的皮试现状,为推进该类药物皮试规范管理提供参考。方法:采用问卷调查和访谈相结合的方式,对国内34家妇女儿童专科医院及21家综合性医院的医护人员、药师和药学部门负责人进行调查,并对数据进行统计和分析。结果:共发放调查问卷55份,回收有效问卷55份,有效回收率为100%;对10家医院的问卷填报人访谈完成良好。各家医院β-内酰胺类抗菌药物皮试比例为19%~100%,平均75%。所有医院均对青霉素类注射剂进行皮试。8家医院对口服青霉素类药品未进行皮试。54家医院(剔除仅有1种抗菌药物品种的1家医院)中,进行头孢菌素类注射液皮试的医院有50家,比例为93%。4家医院对口服头孢菌素类进行皮试,10家医院对碳青霉烯类进行皮试,3家医院对单环β-内酰胺类进行皮试。皮试液种类、皮试液剂量及浓度不一。皮试方法均为皮内注射。26家医院有β-内酰胺类抗菌药物皮试文件统一规定,28家医院无相应规定,1家医院仅对青霉素类皮试有规定。11家医院提供了可查询的近3年β-内酰胺类抗菌药物皮试次数共2 727 714例次,平均每家医院每年82 658例次。23家医院提供了近3年β-内酰胺类抗菌药物输液反应例次共6 187例次,每家医院平均每年约90例次。6家医院提供了按药品化学结构分类统计的数据,总计头孢菌素类皮试次数超过了108万例次,达到了青霉素类皮试次数的2倍多,头孢菌素类皮试消耗大量的人力物力并造成环境污染。结论:目前国内β-内酰胺类抗菌药物皮试执行情况差异较大,尤其是有争议的头孢菌素类药物皮试,有待进行统一规范,以促进抗菌药物合理使用和结构合理化。     

部分医疗机构《β内酰胺类抗菌药物皮肤试验指导原则（2021年版）》的实施情况调查

目的 调查部分医疗机构《β内酰胺类抗菌药物皮肤试验指导原则（2021年版）》的实施情况。方法 通过问卷星调查56家医疗机构头孢菌素类药物皮肤试验（皮试）的管理情况及医务人员对《β内酰胺类抗菌药物皮肤试验指导原则（2021年版）》的掌握程度。结果 回收有效问卷407份（问卷有效率100%）。《β内酰胺类抗菌药物皮肤试验指导原则（2021年版）》颁布后取消头孢菌素类药物常规皮试的医疗机构占比从17.86%提高到58.93%,仍然有32.14%的医疗机构未取消头孢菌素类药物常规皮试。医务人员对患者过敏史的甄别水平较高（占97.79%）、阳性皮试记录结果正确率较高（占96.07%）、大多数医疗机构（占96.43%）开展了严重过敏反应的抢救培训;但对头孢菌素类药物皮试适应证、皮试的意义、阳性/阴性预测值的意义、过敏性休克的抢救用药等掌握程度较低。结论 《β内酰胺类抗菌药物皮肤试验指导原则（2021年版）》实施情况不理想,医务人员对《β内酰胺类抗菌药物皮肤试验指导原则（2021年版）》的掌握程度有待提高。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.