依据目前β-内酰胺类抗菌药物交叉过敏反应研究探索相关规范化管理流程

目的：了解国内外关于β-内酰胺类抗菌药物过敏相关的临床研究及处理流程，探索我国对于这一问题的规范化管理流程。方法：对近年来国内外β-内酰胺类抗菌药物过敏相关的作用机制、流行病学数据及处理流程进行汇总分析。结果：β-内酰胺类抗菌药物交叉过敏反应发生率低，经临床相关的过敏风险评估后大部分患者可安全使用侧链结构不同的β-内酰胺类抗菌药物；结合国外相关处理流程建立了对于β-内酰胺类抗菌药物过敏患者可能的规范化管理流程。结论：对某种β-内酰胺类抗菌药物过敏的患者不应该完全排除使用该类抗菌药物的可能性；可通过制定相关管理流程，加强对β-内酰胺类抗菌药物过敏患者的抗菌药物使用管理。     

β-内酰胺类抗菌药物临床交叉过敏反应的发生机制及美国相关处理流程介绍

目的:了解β-内酰胺类抗菌药物在临床使用中发生交叉过敏反应的机制,为临床合理用药提供参考。方法:结合笔者在美国伊利诺伊大学芝加哥分校(UIC)附属医院进修期间的学习心得,同时根据美国拉什大学医学中心对β-内酰胺类抗菌药物过敏史者的安全用药管理经验,总结β-内酰胺类抗菌药物发生交叉过敏反应的机制,并介绍美国UIC附属医院对β-内酰胺类抗菌药物过敏患者的处理流程。结果:β-内酰胺类抗菌药物发生交叉过敏反应的主要原因是由于药物之间存在相同或相似的侧链,人体内免疫球蛋白E通过识别这些侧链而产生交叉过敏反应。美国UIC附属医院对β-内酰胺类抗菌药物过敏患者的处理流程,包括对患者是否有β-内酰胺类抗菌药物使用指征进行评估,根据评估结果进行规范的青霉素皮试,并采用谨慎渐进式流程用药和快速诱导药物耐受流程进行抗感染治疗。结论:美国UIC附属医院对β-内酰胺类抗菌药物交叉过敏反应患者的处理方法,可为国内临床药师处理可疑β-内酰胺类抗菌药物过敏史者,尤其是针对孕妇、儿童等特殊人群提供新的思路。     

喹诺酮类药物的构效关系及临床应用

近年来喹诺酮类抗菌药发展十分迅速,由于此类药物不易产生耐药性,过敏反应少与其它类抗苗药物无交叉过敏和交叉耐药等优点,临床应用越来越广泛。此类药物的作用机制主要是抑制DNA旋转     

基于实时细胞分析的化合物48/80诱导肥大细胞脱颗粒评价研究

<正>药物引起的过敏/类过敏反应是临床常见的不良反应之一。传统的过敏/类过敏反应评价方法多选用豚鼠,通过考察给药后豚鼠出现的喷嚏、抓鼻、呼吸困难、抽搐昏倒或死亡等现象,以判断药物是否可以引起过敏/类过敏反应[1],存在实验周期性长、灵敏度低、误差大等缺点。大量研究表明[2],     

妇女儿童中药过敏及类过敏反应问题分析

目的提高妇女、儿童的用药安全及用药依从性。方法就妇女、儿童体质特点、常见的引起过敏和类过敏反应的中药、过敏和类过敏反应发生机制和妇女、儿童使用中药应注意的问题等进行分析。结果与结论通过对妇女、儿童中药过敏及类过敏反应的分析,可为妇女、儿童安全用药提供依据。     

碘造影剂过敏样反应发生机制研究进展及防治

目的:综述碘造影剂(ICM)过敏样反应发生机制研究进展。方法:参考国外相关文献,从膜效应、补体系统激活、缓激肽释放、Ig-E介导的抗原抗体反应、T细胞介导的免疫反应这5个方面,对ICM过敏样反应发生机制研究进行综述。结果和结论:ICM过敏样反应中绝大多数属于类过敏反应,真正的过敏反应很少,因此皮肤试验假阴性概率高,大规模推广造影前进行皮试意义不大。     

浅析1990年版中国药典关于药物过敏的规定

由于以往对有过敏反应的药物种类和过敏试验法的认识不一,各地各单位对此规定各异,本文就1990年版中国药典的规定,介绍药典收载的有过敏反应的药物及过敏试验法加以叙述。1990年版中国药典(以下简称药典)有过敏反应叙述的药物达30多种(1985年版24种)。这些药物中,主要有抗生素类、含碘造影剂及抗毒素类等。以往我们对于有过敏反应的药物的认识不一致,一些书刊杂志     

中药制剂致过敏类不良反应的研究进展

随着中医药在国内外认可度的提升,中药制剂的临床使用越来越普遍,随着使用人数的增多,使用过程中的不良反应也日益增多,其中最主要的是过敏类反应。中药制剂过敏类不良反应问题的出现引起用药安全的疑虑,严重制约中药制剂的临床推广应用。综合了近年来临床上有关中药制剂发生的过敏类反应、过敏类反应的机制及临床应对措施的相关研究,归纳总结目前使用中药制剂引起过敏反应的现状、致病特点和相关影响因素,为中药制剂在临床用药安全尽可能避免发生过敏反应提供相关文献参考和理论依据,为临床合理用药提供依据,保障患者用药安全。     

磺胺类药物过敏和交叉过敏的研究进展

磺胺类药物是指含有-SO2NH2结构的药物。磺胺类药物的交叉过敏仍是困扰临床的一个用药难题。有磺胺类抗菌药过敏史的患者在临床上并不罕见,这些患者是否可以使用其他磺胺类药物,相关药品说明书的描述并不一致,也无标准的操作流程或指南。本文回顾了磺胺类抗菌药发生超敏反应的机制,发现其发生主要与磺胺类抗菌药N4位的芳香胺取代基和N1位的杂环取代基有关,而多数磺胺类非抗菌药(如呋塞米、噻嗪类利尿剂、塞来昔布等)并不含有这两个取代基,因此磺胺类抗菌药和非抗菌药之间发生交叉过敏的可能性较低。此外,本文也对磺胺类药物交叉过敏的相关临床研究进行了回顾。一个大规模的回顾性研究提示,有磺胺类抗菌药过敏史者使用磺胺类非抗菌药过敏反应的发生率较无磺胺过敏史者高,但并非与磺胺基团有关,而是和患者本身过敏反应易感性高有关。磺胺类抗菌药和非抗菌药之间发生交叉过敏的理论和循证依据尚不充分,但鉴于有磺胺类抗菌药过敏史的患者对药物过敏的易感性较高,这些患者是否可使用其他磺胺类药物,取决于相关药品说明书的规定、既往发生过敏反应的严重程度以及是否有其他替代药物。     

避免药物交叉过敏

药物过敏是用药中常见的不良反应，我们不仅要注意某种药物所致的过敏反应，也要关注药物间的交叉过敏现象。所谓药物交叉过敏，是指患者已经对某一种药物发生了过敏反应，以后使用的另一种药物，虽然与首次发生过敏的药物不同，但是在化学结构上与首次发生过敏的药物相似，同样会发生药物过敏反应。     

非离子型冠脉造影剂致急性严重过敏样反应的病例分析

目的对非离子型冠脉造影剂引起的急性严重过敏样反应进行总结和分析。方法回顾总结2007年12月至2009年12月在我院进行冠状动脉造影和/或介入治疗的24314例患者,对发生冠脉造影剂引起的急性严重过敏样反应的病例进行研究,分析其临床特点。结果9例患者在接受非离子型碘造影剂血管内注射后1小时之内发生严重过敏样反应,发生率0.037%,其临床主要表现为血压突然降低,伴不同程度的心律失常,及其他系统的伴随症状。给予吸氧、补液以及大剂量应用升压药物（尤其是肾上腺素）和糖皮质激素等治疗可有效缓解症状。结论非离子型冠脉造影剂在临床应用中总的安全性良好,但在应用过程中应重视急性严重过敏样反应的识别与处理。     

注射用替加环素临床前安全性研究

目的 评价注射用替加环素的安全性。方法 对注射用替加环素进行血管刺激、肌肉刺激、溶血性及被动皮肤过敏、全身主动过敏性、类过敏性试验。结果 注射用替加环素对血管无明显刺激性、对肌肉组织产生轻度可逆性的刺激,对家兔红细胞无溶血、凝聚作用,大鼠被动皮肤过敏反应（PCA）试验未出现过敏反应;豚鼠全身主动过敏反应（ASA）试验部分豚鼠出现过敏反应;注射用替加环素与已上市药品Tygacil 在同等剂量下,豚鼠出现同等程度的类过敏反应。结论 注射用替加环素可能会引起肌肉刺激性及过敏、类过敏反应,临床应用时应关注患者给药后的反应。     

Preventing and managing drug-induced anaphylaxis.

Drug-induced anaphylaxis and anaphylactoid reactions have increased in frequency with more widespread use of pharmaceutical agents. Anaphylaxis is a systemic, severe immediate hypersensitivity reaction caused by immunoglobulin (Ig) E-mediated immunological release of mediators of mast cells and basophils. An anaphylactoid reaction is an event similar to anaphylaxis but is not mediated by IgE. The incidence of anaphylactic or anaphylactoid reactions differs amongst classes of medications. Antibacterials are the most usual offenders, and penicillins are the most studied. Other compounds commonly causing reactions include non-steroidal anti-inflammatory drugs, anaesthetics, muscle relaxants, latex and radiocontrast media. Prevention, if possible, is the purpose of detailed patient history taking and physical examination. Simple strategies can be employed to decrease the risk of anaphylaxis. These include consideration of the route of drug administration, identification of patients with known causes of anaphylaxis, and the knowledge that certain medications cross react and are contraindicated in those with known history of anaphylaxis. Tests are available, and include IgE-specific skin tests and radioallergosorbent tests. Penicillins are the only compounds whose antigenic determinants are well documented, it is therefore difficult to determine the negative predictive value of other compounds tested. Oral challenge remains an alternative, though entails risk. Desensitisation procedures, as well as gradual dose escalation protocols, are available and can be implemented based on patient history and diagnostic testing. The management of anaphylaxis is based on control of the airway, breathing and circulation. Treatment consists of epinephrine (adrenaline) and supportive measures. Rapid diagnosis and intervention are important in these life-threatening reactions. After stabilisation, all individuals with a documented history of anaphylaxis require a Medic-Alert bracelet or necklace, and an identification card for their wallet or purse.     

Histamine metabolism after adverse reactions due to d-tubocurarine administration

We investigated histamine release in five female patients, submitted for gynaecological surgery, after intravenous administration of the neuromuscular blocking agent d-tubocurarine. In these patients, we measured the plasma levels of histamine and its metabolites, N tau-methylhistamine and N tau-methylimidazoleacetic acid, making use of mass fragmentographic methods. The newly developed determination of plasma N tau-methylimidazoleacetic acid had a within-day coefficient of variation of 2.7% (n = 10). Normal values of N tau-methylimidazoleacetic acid in plasma ranged from 41.3-75.6 nmol/l (n = 13). All five patients developed anaphylactoid reactions: two patients showed severe systemic reactions, one patient a minor systemic reaction and two had skin reactions only. Plasma histamine and N tau-methylhistamine levels appeared to be the most reliable biochemical parameters for confirming both the occurrence and severity of an anaphylactoid reaction. In comparison with plasma histamine, the determination of plasma N tau-methylhistamine is less hampered by artefacts caused by blood collection and plasma preparation. Together with the fact that the increase in plasma N tau-methylhistamine levels after anaphylactoid reactions lasts much longer than the increase in plasma histamine levels, this leads to the conclusion that the determination of plasma N tau-methylhistamine is a useful retrospective parameter for histamine release in this type of pathological state. The plasma N tau-methylimidazoleacetic acid levels fluctuated considerably, showing only a significant increase after administration of d-tubocurarine in the two patients who had severe anaphylactoid reactions. This parameter is, therefore, less useful in such studies.     

Tween‐80 and impurity induce anaphylactoid reaction in zebrafish

A number of recent reports suspected that Tween‐80 in injectable medicines, including traditional Chinese medicine injections could cause life‐threatening anaphylactoid reaction, but no sound conclusion was drawn. A drug‐induced anaphylactoid reaction is hard to be assayed in vitro and in conventional animal models. In this study, we developed a microplate‐based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction and live whole zebrafish mast cell tryptase activity was quantitatively measured at a wavelength of 405 nm using N‐benzoyl‐dl ‐arginine p‐nitroanilide as a substrate. We assessed 10 batches of Tween‐80 solutions from various national and international suppliers and three Tween‐80 impurities (ethylene glycol, 2‐chloroethanol and hydrogen peroxide) in this model and found that three batches of Tween‐80 (nos 2, 20080709 and 20080616) and one Tween‐80 impurity, hydrogen peroxide (H₂O₂), induced anaphylactoid reactions in zebrafish. Furthermore, we found that H₂O₂ residue and peroxide value were much higher in Tween‐80 samples 2, 20080709 and 20080616. These findings suggest that H₂O₂ residue in combination with oxidized fatty acid residues (measured as peroxide value) or more likely the oxidized fatty acid residues in Tween‐80 samples, but not Tween‐80 itself, may induce anaphylactoid reaction. High‐throughput zebrafish tryptase assay developed in this report could be used for assessing safety of Tween‐80‐containing injectable medicines and potentially for screening novel mast cell‐modulating drugs. Copyright © 2014 John Wiley & Sons, Ltd.     

围手术期地塞米松过敏的研究进展

围手术期地塞米松常应用于抗过敏治疗,近年来关于地塞米松引起的过敏反应的报道也越来越多。这些反应主要包括IgE介导的过敏反应和药物直接刺激释放组胺引起的类过敏反应。地塞米松引起的过敏反应是一种全身性或系统性反应,症状可从局部至全身。围手术期过敏原检测起着重要的作用,这些检测方法包括皮肤过敏试验,血清中组胺、类胰蛋白酶和IgE抗体浓度检测等。另外过敏反应发生后及时供氧、扩容和肾上腺素的应用是抢救患者的关键。     

Anaphylactoid oedema produced in rats by certain dextrins

The author has previously shown the conditioning role of the anaphylactoid reaction in the calcification of the snout and paws of the rat after the injection of certain metallic compounds. The present experiments show that it is the dextrin fraction of these compounds which causes these anaphylactoid phenomena before the calcifying response. This fact deserves special attention since dextrin is frequently used in the preparation of certain drugs.     

类过敏反应的研究进展

目的对类过敏反应的症状特点、发生机理、评价方法及存在的问题进行了综述和分析,为类过敏反应的深入研究提供文献依据。方法对近年来有关类过敏反应的国内外文献进行了整理与归纳。结果虽然类过敏反应的症状表现与过敏反应相似,但两者发生机制并不相同,其无需提前致敏、抗体介导,首次接触即可发生,危害严重。目前,类过敏反应的临床前评价方法主要有动物实验和细胞实验,检测指标有组胺、IgE等,其诊断需结合症状特点及生物指标综合判断。结论亟待建立可行的有关类过敏反应的临床前评价方法。     

Anaphylactoid reaction to enoxaparin in a patient with deep venous thrombosis

A 40-year-old Caucasian man diagnosed with right deep venous thrombosis secondary to trauma was treated with subcutaneous enoxaparin. Within minutes of administering the first dose (1 mg/kg), he experienced an apparent anaphylactoid reaction; symptoms were abdominal pruritus, severe cough, shortness of breath, anxiety, and global pruritus. Physical examination revealed an erythematous macular rash and stridor on auscultation secondary to cervical edema. No other drugs were given before the reaction occurred, and the patient's only drug therapy at home had consisted of a daily multivitamin, and acetaminophen and ibuprofen as needed. Administration of low-molecular-weight heparins such as enoxaparin is increasing, and clinicians must be aware of the potential for adverse drug events such as hypersensitivity reactions.     

7种中药注射剂对Beagle犬类过敏反应研究

 目的：选择临床报告过敏性休克排名较前的7种中药注射剂进行Beagle犬类过敏反应试验（anaphylactoid reaction）,并探讨聚山梨酯80（Tween 80）对中药注射剂致敏性的影响。方法：通过一次静脉恒速注射各种中药注射剂,观察Beagle犬的反应症状,检测血浆中组胺、免疫球蛋白E （immunoglobulin E,IgE）、免疫球蛋白G（immunoglobulin,IgG）和免疫球蛋白M （immunoglobulin M,IgM）含量。结果：根据行为症状和组胺含量升高综合判断为类过敏反应强阳性者有含Tween 80的鱼腥草、脉络宁和复方丹参注射剂,其他为阳性。结论：7种中药注射剂均出现类过敏反应,吐温80是导致含Tween 80的中药注射剂类过敏反应的主要诱因之一,但非惟一原因,尚存在一些其他诱发物质,需进一步研究。