与磺胺类抗菌药过敏有关的交叉过敏

磺胺类抗菌药是指结构中含磺酰芳胺基团的药物,与本类药物有交叉过敏反应的药物一般结构中含磺酰氨基。本文参考药品说明书和相关文献汇总与磺胺类抗菌药有交叉过敏反应的药物,简述了交叉过敏反应的药学监护点和处理措施。临床应谨慎使用此类药物,避免交叉过敏反应的发生。     

磺胺类药物交叉过敏管理的临床调查和现状分析

目的:调查某院磺胺类药物使用现状,探讨该类药物交叉过敏管理的必要性.方法:通过病历系统筛选和统计该院磺胺类药物使用情况,包括主要种类、既往过敏患者使用情况等.设计问卷调查医疗人员对磺胺类药物过敏的认知情况,包括磺胺类药物的识别量,及其过敏和交叉过敏掌握情况.结果:我院主要使用的磺胺类药物有13种.2019年10月～20...     

国内外常用磺脲类药物的药品说明书中磺胺类过敏事项标注情况分析

目的:了解磺脲类药物的药品说明书中磺胺类过敏事项标注情况,为促进该类药物的临床合理应用提供参考。方法:于2018年10月通过查询MCDEX软件(网络版)、美国食品药品监督管理局网站的Drugs@FDA以及DailyMed网站、欧洲药品管理局网站以及英国电子医药汇编网站,收集国内外常用磺脲类药物的药品说明书,将磺胺类过敏事项标注分为未标注磺胺类过敏事项、仅标注磺胺类过敏禁用、仅标注磺脲类过敏禁用以及同时标注磺胺类和磺脲类过敏禁用,并计算磺胺类过敏禁用的标注比例。结果:在174份国内药品说明书中有格列齐特67份、格列吡嗪48份、格列本脲23份、格列美脲23份、格列喹酮13份;不同的药品生产厂家在格列喹酮和格列本脲的磺胺类过敏事项标注上取得了较为一致的看法,在药品说明书中标注磺胺类过敏禁用的比例分别为100%和95.65%;在格列吡嗪、格列美脲、格列齐特的磺胺类过敏事项标注上存在较大分歧,标注磺胺类过敏禁用的比例分别为70.83%、65.22%、49.25%。在13份国外药品说明书中有格列本脲4份、格列吡嗪3份、格列美脲3份、格列齐特3份;有7份药品说明书标注磺胺类过敏禁用;但美国与欧洲磺脲类药物的药品说明书在磺胺类过敏事项标注上存在较大差异。结论:国内外磺脲类药物的药品说明书中磺胺类过敏事项标注情况存在较大差异,说明对于磺胺类药物交叉过敏在磺胺类过敏患者中的临床意义存在不同看法,反映出对于磺胺类药物交叉过敏存在较大争议。这需要从科研工作者、医药协会、药品生产厂家、医务人员和患者等多方面共同推进对磺胺类药物交叉过敏的研究,明确其机制和临床意义。     

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。     

警惕药物交叉过敏及复方制剂中的致敏药物

目的:为临床安全用药提供参考。方法:参考药品说明书和相关文献,归类总结。结果:制定交叉过敏药物及复方制剂、中成药中的致敏药物表及药物、食物交叉过敏表。结论:临床应谨慎使用相关药物,避免交叉过敏反应的发生。     

临床用药过程中应注意的交叉过敏

药物过敏反应是药物副作用中较为严重的不良反应,不同于一般意义的副作用,是机体受药物后所发生的不正常免疫反应,这种反应的发生与药物剂量无关或关系甚少,治疗量或极小量都可发生,多见过敏体质病人,反应性质各不相同,不易预知。现代制药业迅猛发展,新药层出不穷,但大多数新药均是在原有基础改进而成,有原共性。系统阐明各类药物之间的交叉过敏具有实际临床意义,对于安全用药更为重要,应     

交叉过敏的临床药学干预

目的促进临床医护人员对药物交叉过敏的意识,防范用药失误发生。方法对药物说明书禁忌症中有关交叉过敏的描述进行信息分析和数据挖掘。对药物咨询、用药失误和近似错误在线呈报系统记录进行分析。实施临床药学综合性干预措施,并评估干预效果。结果除药理作用相似的27类同类药品交叉过敏外,还存在涉及多个药理作用类别的交叉过敏药物7大类。化学结构相似是引起交叉过敏的主要原因。一些交叉过敏禁忌的描述涉及赋形剂。部分禁忌症有关交叉过敏的描述不科学,缺乏临床指导意义。部分同类品种以及国内产品与进口产品的相关描述可能存在差异。涉及多个药理作用类别的交叉过敏问题比较隐蔽。药师进行持续的临床药学干预后,临床对交叉过敏的认知水平有大幅提高,近似错误和用药失误的发生下降97%。结论若不注意交叉过敏问题,临床会有严重的安全隐患。药师经过临床药学综合干预,效果显著。信息技术的应用以及数据的维护至关重要。     

磺胺过敏患者使用磺脲类降糖药2例安全性分析

目的:探索磺胺过敏的患者使用磺脲类降糖药的安全性.方法:收集南昌大学第一附属医院2019年10月、11月收治的2例磺胺过敏患者使用磺脲类降糖药的病例,并查阅国内外相关文献.结果:被收集病例均未观察到过敏反应,各国在磺脲类药品说明书的标注差异较大.结论:考虑《磺脲类药物临床应用专家共识(2016年版)》提出磺胺过敏禁用,...     

交叉过敏的临床药学干预

目的提高医务人员对于临床药物交叉过敏的防范意识,降低用药差错的发生率。方法对用药咨询、用药失误以及近似错误的在线报告系统的以往记录进行统计分析,对药品说明书中禁忌症项关于交叉过敏症状的描述进行数据挖掘以及信息分析,并对医院实行临床药学干预的效果进行评估。结果药物的化学结构相似是造成交叉过敏的主要因素。临床上易发生交叉过敏的药物除了27类药理作用相似的同类药品外,还有7类涉及多种药理作用类别的药物。有部分药物的禁忌症与交叉过敏有关的描述缺乏科学性,没有临床指导意义,部分药物进口产品和国内的产品之间也存在一定的差异。但是在药师对临床药学进行持续的干预之后,整个临床方面对药物交叉过敏的意识有大幅度的提升。结论药师对临床药学的干预对于交叉过敏的问题有非常重要的意义。     

Study on the dipeptide vinyl sulfonamide derivatives as proteasome inhibitor

On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.     

Chloroquinoxaline sulfonamide: A sulfanilamide antitumor agent entering clinical trials

Summary Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame.The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half-lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45–132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans.Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m².     

Acetylator phenotype and genotype in HIV-infected patients with and without sulfonamide hypersensitivity

Adverse reactions to sulfonamides occur at a higher frequency in patients infected with the human immunodeficiency virus (HIV) than noninfected patients. Some studies have suggested that patients with the slow acetylator phenotype are predisposed to these reactions, whereas other studies suggest that the slow acetylator genotype is not a predisposing factor. To rationalize these seemingly contradictory observations, the authors determined the N-acetyltransferase 2 (NAT2) genotype and phenotype in patients with and without a history of hypersensitivity reactions to sulfonamides. HIV-infected patients with a history of a delayed-type hypersensitivity reaction to trimethoprim-sulfamethoxazole were enrolled, along with a group of AIDS patients with no history of hypersensitivity (delayed or immediate). NAT2 phenotype was determined in both groups using dapsone, while the genotype was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Ten of 14 patients (71%) with a history of hypersensitivity exhibited the slow acetylator phenotype, while 8 of 14 patients (57%) without such a history exhibited this same phenotype (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 0.4-9.0; p = 0.69, Fisher's Exact Test). While 9 of 14 patients (64%) with a history of hypersensitivity exhibited a slow acetylator genotype, only 4 of 14 patients (29%) without such a history exhibited this genotype (ns). There were more instances of discordance between deduced and actual phenotype in the nonhypersensitive patients (n = 4) than in the hypersensitive patients (n = 1). The reported higher frequency of the slow acetylator phenotype among patients with a history of hypersensitivity to sulfonamides does not appear to be explained by metabolic changes that would cause discordance between acetylator genotype and phenotype.     

抗耐药菌药物研究进展

近年来医药界十分关注抗耐药菌药物研究，有两种主要抗耐甲氧西林金黄色葡萄球菌（MRSA），耐青霉素肺炎链球菌（PRSP），耐万古霉素肠球菌（VRE）等革兰阳性耐药菌的新药上市，有一批新广谱抗生素临床应用，还有若干颇具开发前景的化合物正在研究中，本文分3个部分综述了近年来研究进展（1）新型结构，新作用机制、新作用靶位的新药研究；（2）抗生素与合成抗菌药的结构修饰；（3）增强与保护抗菌药物性能的物质诸如抗菌增强剂，抗生素酶抑制剂，膜渗透性增强剂，外排泵抑制剂等研究。     

Evaluation of sulfonamide detoxification pathways in haematologic malignancy patients prior to intermittent trimethoprim-sulfamethoxazole prophylaxis

AIMS

Patients with haematologic malignancies have a reportedly high incidence of sulfamethoxazole (SMX) hypersensitivity. The objective of this study was to determine whether deficiencies in sulfonamide detoxification pathways, to include glutathione (GSH) and ascorbate (AA), and cytochrome b₅ (b5) and cytochrome b₅ reductase (b5R), were prevalent in these patients. A secondary pilot objective was to determine whether the incidence of drug hypersensitivity following intermittent trimethoprim-SMX (TMP-SMX) prophylaxis approached that reported for high dose daily regimens.

METHODS

Forty adult patients with haematologic malignancies (HM) and 35 healthy adults were studied; an additional 13 HM patients taking ascorbate supplements (HM-AA) were also evaluated. Twenty-two of 40 HM patients were prescribed and were compliant with TMP-SMX 960 mg three to four times weekly.

RESULTS

There were no significant differences between HM and healthy groups in plasma AA (median 37.2 µmvs. 33.9 µm) or red blood cell GSH (1.9 mmvs. 1.8 mm). However, plasma AA was correlated significantly with leucocyte b5/b5R reduction (r = 0.39, P = 0.002). Deficient b5/b5R activities were not found in HM patients. In fact, patients with chronic lymphocytic leukaemia or myeloma had significantly higher median activities (80.7 µmol mg^–1 min⁻¹) than controls (18.9 µmol mg^–1 min⁻¹, P = 0.008). After 3–4 weeks of treatment, no patients developed SMX-specific T cells and only one patient developed rash.

CONCLUSIONS

Deficiencies of blood antioxidants and b5/b5R reduction were not found in this population with haematologic malignancies, and the development of skin rash and drug-specific T cells appeared to be uncommon with intermittent TMP-SMX prophylaxis.     

抗菌药物与洛匹那韦/利托那韦相互作用研究进展

口服抗病毒药洛匹那韦/利托那韦的抗病毒作用受很多因素的影响,如患者性别、种族、合并症、用药依从性等。与其他药物的相互作用也是影响洛匹那韦/利托那韦抗病毒的重要因素之一,其中一些抗菌药物对洛匹那韦/利托那韦的影响较大且机制复杂,作用持续时间也较长,对于联用洛匹那韦/利托那韦合并细菌或真菌感染的患者,抗菌药物的选择与监测更为重要。本文通过综述国内外相关研究,探讨和总结洛匹那韦/利托那韦与抗菌药物的相互作用机制和应对策略,比较不同抗菌药物的药动学特性及与洛匹那韦/利托那韦相互作用的差异,从而为抗菌药物的选择和相应剂量的调整提供参考,降低患者用药风险,提高安全性。     

D‐420720, A novel orally active sulfonamide compound dipeptidyl peptidase IV inhibitor: structure and activity relationship of arylsulfonamide to dipeptidyl peptidase IV inhibition

Diabetes mellitus is a chronic disease characteristic of poor glucose homeostasis that requires constant monitoring and adjustment of blood glucose levels by exogenous intervention. Glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) are two incretin peptide hormones secreted from the intestine to synergize insulin's function at lowering blood glucose. The effects of GLP‐1 or GIP administration are short‐lived because they are rapidly inactivated by circulating dipeptidyl peptidase IV (DPP‐IV). Therefore, DPP‐IV inhibitors have been suggested to be a new class of molecule for treating hyperglycemic conditions in diabetic patients. The recent approval of Merck's Sitagliptin (a DPP‐IV‐specific inhibitor) indicates that DPP‐IV inhibition is a good target for new therapeutic agent development. The present study was conducted to evaluate the efficacies of a series of dipeptidyl derivatives with a sulfonamide moiety as DPP‐IV inhibitors. Among these compounds, D‐420720 was a potent inhibitor (K_i=39 nM), with a selectivity of 9160‐fold over the DPP‐II isozyme and elicits a hypoglycemic effect on oral glucose tolerance test with normal male ICR mice. Drug Dev Res 69: 514–525, 2008. © 2008 Wiley‐Liss, Inc.     

某三甲综合医院2017—2018年临床分离细菌耐药性监测

目的对某三甲综合医院2017年—2018年临床分离细菌的耐药性进行监测,为抗菌药物合理应用提供参考依据。方法收集某三甲综合医院2017年1月1日—2018年12月31日临床分离细菌,通过法国梅里埃VITEK 2 compact分析仪进行细菌鉴定,MIC法和纸片扩散(K-B)法进行药敏试验,并使用WHONET 5.6软件对资料进行统计分析。结果共收集非重复细菌3854株,有54.9%细菌来源于呼吸道标本,有25.6%细菌分离自ICU病区,革兰阴性菌占73.9%(2849/3854),以大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌、嗜麦芽寡养假单胞菌和鲍曼不动杆菌为主,分别占29.2%、13.0%、11.2%、6.0%、4.4%;革兰阳性菌占26.1%(1005/3854),以金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和屎肠球菌为主,分别占10.6%、3.2%、2.0%、1.4%。葡萄球菌对青霉素G100.0%耐药,对红霉素和克林霉素耐药率>60.0%,未出现万古霉素、利奈唑胺、替加环素耐药菌株,耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为58.8%、80.1%。除氯霉素外,屎肠球菌的耐药率显著高于粪肠球菌,对红霉素、四环素、环丙沙星、左氧氟沙星和青霉素G的耐药率均>80.0%,对万古霉素耐药率为1.8%。肺炎链球菌对克林霉素和四环素的耐药率>90.0%,对青霉素G的耐药率为5.3%。β-溶血链球菌和草绿色链球菌对红霉素和克林霉素的耐药率均>80.0%,对青霉素G的耐药率分别为6.3%、2.8%。大肠埃希菌产超广谱β-内酰胺酶(ESBLs)的检出率为52.1%,对氨苄西林和头孢唑啉的耐药率>65.0%,对环丙沙星和左氧氟沙星耐药率分别为46.9%和43.4%,对亚胺培南和美罗培南的耐药率分别为2.6%、3.2%。肺炎克雷伯菌和奇异变形杆菌产ESBLs的检出率分别为31.7%、13.8%,对头孢他啶、头孢吡肟、妥布霉素、哌拉西林/三唑巴坦、头孢替坦和阿米卡星的耐药率<10.0%,对亚胺培南的耐药率分别为2.5%、0.8%。铜绿假单胞菌对左氧氟沙星、庆大霉素、妥布霉素和阿米卡星的耐药率<25.0%,对亚胺培南的耐率为44.5%。鲍曼不动杆菌对多种抗菌药物耐药率均>40.0%,对亚胺培南的耐药率为41.3%。嗜麦芽寡养单胞菌主要来源于ICU病区(74.1%),对左氧氟沙星的耐药率最低(1.7%),对头孢他啶的耐药率高达82.7%。流感嗜血杆菌和淋病奈瑟菌β-内酰胺酶检出率分别为52.1%、21.4%,对头孢曲松和头孢噻肟100.0%敏感。结论定期对临床分离细菌的耐药性进行监测,对提高感染患者的抗感染治疗效果和延缓耐药性进一步上升具有重要意义。