浅谈中药注射剂的不良反应与应用原则

继2006年"鱼腥草注射液暂停使用"以来,"刺五加注射液不良反应致死事件"的爆发以及青海双黄连注射液致死事件的发生,使得中药注射液的安全性再度引起关注.     

浅析中药注射液体外类过敏检测方法

随着中药注射液的广泛应用,对其严重不良反应之一类过敏反应的研究凸显出重大意义。本文就检测方法中细胞株、阳性药、检测指标及ELISA试剂盒等方面进行综述,旨在优化中药注射液体外类过敏的检测方法。     

11例艾迪注射液不良反应文献分析

目的 探讨艾迪注射液不良反应发生的一般规律和特点,为临床合理用药提供参考.方法 检索相关文献,对国内医药期刊报道的有关艾迪注射液不良反应的文献进行统计分析.结果 艾迪注射液的不良反应主要发生在中老年患者,并以男性为主(63.64%),反应可发生在用药过程、用药后和多次用药后,以用药过程中发生不良反应的情况为多(36.37%).不良反应主要为过敏反应(54.55%),主要涉及皮肤及其附件系统和呼吸系统.值得注意的是其可能引起左心衰竭、冠心病和血小板减少等严重损害.结论 临床应加强艾迪注射液的不良反应监测,警惕严重不良反应的发生.     

穿琥宁注射液不良反应的病例汇总

穿琥宁注射液被临床广泛应用于治疗抗病毒和广谱抗菌的双重作用。近年来报道的穿琥宁注射液不良反应有腹痛、腹泻,过敏反应伴脑水肿、严重呼吸困难、哮喘样发作伴休克、药物热、惊厥、肌肉震颤、寒战发热、皮疹、白细胞锐减、血小板减少等。在临床应用中应当加以重视。     

鱼腥草、穿琥宁注射液治疗小儿急性上呼吸道感染

我院儿科自2002年10月-2005年6月期间应用鱼腥草、穿琥宁注射液治疗小儿急性上呼吸道感染取得较为满意疗效，现特报道如下。     

30例细辛脑注射液不良反应分析

目的 通过对我院门诊30例注射用细辛脑所致的不良反应报告分析,探讨该药不良反应的类型、规律及趋势.方法对30例注射用细辛脑所致的不良反应报告进行归类及分析.结果 共发现注射用细辛脑所致的不良反应30例,其中全身过敏反应18例,消化系统损害7例,皮肤及其他附件损害4例,其他不良反应1例.结论 细辛脑注射液所致的临床ADR/ADE应引起临床高度重视,建议完善药品说明书.     

中山大学附属第一医院2017年输血不良反应调查

目的 通过对我院临床输血不良反应情况的回顾性分析,降低输血不良反应的发生,保障临床输血安全。方法 收集我院2017年1月1日~12月31日输血不良反应病例,进行分类分析。结果 共发生输血不良反应143例,发生率0.50%,其中107例为过敏反应,占比74.82%,32例为非溶血性发热反应,占比22.38%,过敏反应合并非溶血性发热反应有4例,占比2.80%。结论 我院的输血不良反应率较低,主要的不良反应类型是由于输血小板制品引起的过敏反应。临床上应对输血进行严格掌握,合理实施输血治疗措施,降低不良反应发生率,提高输血安全。     

鱼腥草和病毒唑治疗急性上呼吸道感染疗效对比

重症上呼吸道感染治疗组80例、对照组64例,分别以鱼腥草注射液、病毒唑治疗.治疗组总有效率达87.5%,高于对照组的68.8%,(p＜0.01).鱼腥草具有抗炎、抗病毒、增强机体免疫力等作用 , 对上呼吸道有较好疗效.     

中药注射剂过敏反应20例分析

当前中药注射剂作为抗病毒药和抗生素的西药替代品,因其免做皮试、不良反应少、使用方便而被广泛使用.我院儿科近五年来先后使用双黄连、清开灵、鱼腥草、莪术油、肿节风注射剂,出现20起较严重的不良反应,应引起大家的重视.     

鱼腥草和病毒唑治疗急性上呼吸道感染疗效对比

重症上呼吸道感染治疗组80例，对照组64例，分别以鱼腥草注射液、病毒唑治疗。治疗组总有效率达87．5％，高于对照组的68．8％，（P＜0．01）。鱼腥草具有抗炎、抗病毒、增强机体免疫力等作用，对上呼吸道有较好疗效。     

166例双黄连注射剂不良反应分析

目的 研究双黄连注射剂不良反应发生的规律及其特点,为临床用药提供参考。方法 通过文献检索,对166例双黄连注射剂的不良反应进行分析和归纳。结果 双黄连注射剂的不良反应无性别、年龄的差异,类型上主要为变态反应(71.28%)。结论 在了解双黄连注射剂不良反应产生因素的基础上,通过合理用药,可预防和减少其不良反应。     

Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline in humans

Caffeine (CAF) impedes insulin-mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 n m ). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 n m ) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether or not they elicit an additive response on IMGD. We hypothesized that CAF + ADR would elicit a greater effect than either CAF or ADR alone (i.e. that CAF effects would not be solely attributed to ADR). Subjects ( n = 8) completed four trials in a randomized manner. An isoglycaemic–hyperinsulinaemic clamp was performed 30 min after the following treatments were administered: (1) placebo capsules and saline infusion ([ADR]= 0.29 n m ) (PL trial), (2) CAF capsules (dose = 5 mg kg⁻¹) and saline infusion ([ADR]= 0.62 n m ) (CAF trial), (3) PL capsules and ADR infusion ([ADR]= 1.19 n m ) (ADR trial), and (4) CAF capsules (dose = 5 mg kg⁻¹) and ADR infusion ([ADR]= 0.93 n m ) (CAF + ADR trial). As expected, CAF, ADR and CAF + ADR decreased ( P ≤ 0.05) IMGD compared to PL. CAF + ADR resulted in a more pronounced decrease in IMGD versus PL (42%) compared to CAF (26%) or ADR (24%) alone; however, the effect was not fully additive ( P = 0.08). Furthermore, CAF decreased IMGD to a similar magnitude as ADR despite a 50% lower [ADR]. In summary, while ADR contributes to the CAF-induced impairment in IMGD, it is not solely responsible for caffeine's effects.     

Synthesis and cytotoxic activity of doxorubicin bound to poly(α-malic acid) via ester or amide bonds

Poly(α-malic acid) is of interest for the application as a biodegradable and bioadsorbable drug carrier, which has pendent reactive carboxylic acid groups. In order to provide a biodegradable macromolecular prodrug of doxorubicin (adriamycin, ADR), reducing the side-effects of ADR and exhibiting effective antitumor activity, ADR residues were covalently attched to poly(α-malic acid) via ester or amide bonds to give poly(α-malic acid)/ester/ADR conjugate 1 or poly(α-malic acid)/amide/ADR conjugate 2 , respectively. The release rate of ADR from the poly(α-malic acid)/ester/ADR conjugate 1 was faster than that from the poly(α-malic acid)/amide/ADR conjugate 2 in buffer solution (pH 7,4) at 37°C. While the cytotoxic activity of poly(α-malic acid)/ester/ADR conjugate 1 is as strong as that of free ADR against p388D₁ lymphocytic leukemia cells in vitro, the cytotoxic activity of poly(α-malic acid)/amide/ADR conjugate 2 is much lower.     

磁导向阿霉素-羧甲基葡聚糖磁性毫微粒的毒性的研究

以阿霉素(ADR)为药物模型，制备了阿霉素—羧甲基葡聚糖磁性毫微粒(ADR—CMD MNPs)，对比研究了静脉给药后其与阿霉素普通制剂对小鼠的急性毒性作用、累积毒性作用以及药物在动物心肌组织的分布情况，结果表明：相对于普通制剂，阿霉素的磁性毫微粒制剂的急性毒性明显降低，LD50值达到阿霉素普通制剂的5.06倍，连续给药情况下小鼠的死亡率、体重和白细胞损失都有明显下降；药物分布实验表明阿霉素磁性毫微粒制剂静脉给药后在小鼠心肌组织中的浓度和积累作用明显低于普通制剂，这对降低阿霉素固有的对心肌组织毒副作用非常有利。     

我院2017年272例药品不良反应的原因分析和对策研究

目的 了解我院药品不良反应（ADR）发生的规律和特点,分析原因,探讨对策,为临床合理用药提供依据。方法 采用回顾性分析方法,对我院2017年上报的272例ADR报告内容进行统计分析。结果 272例ADR报告中,男性142例（52.21%）,女性130例（47.79%）,60岁以上的老年患者ADR发生率较高（38.24%）;引发ADR的药物种类以抗感染药物最高,占26.84%,抗肿瘤药位居第二,为16.18%;ADR涉及的药物给药途径中静脉给药所占比例居首位,为72.06%,其次为口服;ADR以皮肤及附件系统损害最多见（38.24%）,其次是消化系统症状（19.12%）,如恶心、呕吐、腹胀、腹泻等。结论 人口老龄化和药物滥用等导致ADR更易发生,我们需要不断完善现有的药品法律法规,优化ADR上报体系,提高药学服务水平,促进合理用药。     

A quantitative approach of using genetic algorithm in designing a probability scoring system of an adverse drug reaction assessment system

BACKGROUND: The detrimental effects of adverse drug reactions (ADRs) are well established. Hence, precise and accurate assessment of ADRs' causality which can differentiate signal from noise is crucial in screening, management and minimisation of ADRs. OBJECTIVE: The current study reported our attempt to improve the scoring system of a previously published algorithm of ADR assessment by our group using a genetic algorithm approach so that the final score can measure the probability of ADR causality. DESIGN: Using ADR cases obtained from the Centre for Drug Administration, the national centre for pharmacovigilance in Singapore, with known causality probability values as reference points, rules were developed to define possible combinations of criteria for 'Definite' ADR cases and 'Probable' ADR cases. A new scoring system was developed using these parameters with the help of genetic algorithm, and tested on 37 'Definite' and 431 'Not Definite' ADR cases. In addition, sensitivity and specificity analysis were performed to allow a comparison of performance between our algorithm and that used by the Adverse Drug Reaction Advisory Committee in Australia (ADRAC). RESULTS: The new scoring system is able to provide a probability of the causality of an ADR by a suspected drug. When applied to the 'Definite' and 'Not Definite' ADR reports, the new algorithm gave a sensitivity of 83.8% and specificity of 71.0%. CONCLUSIONS: Using a quantitative method of assessing causality in the new algorithm allows rare and new ADRs to be more readily identified since a quantitative score can give a more precise degree of ADR causality. This scoring system that provides a probability score would help to make this algorithm more informative and assistive for clinicians, regulatory agencies or pharmaceutical companies to generate ADR alerts. The higher sensitivity value displayed by our algorithm also shows that it would be a good ADR screening tool.     

DAC-树脂血液灌流与门脉输注阿霉素联合应用对心肌丙二醛含量的影响

本文的研究结果显示，心肌的丙二醛（ＭＤＡ）含量随门脉输注ＡＤＲ剂量的增加而增高呈正相关（ｒ＝０．８９７７）。联合应用ＤＡＣ－树脂血液灌流（ＤＨＰ）较对照灌流组明显降低了ＡＤＲ５ｍｇ／ｋｇ和１０ｍｇ／ｋｇ组急性期（Ｐ分别＜０．００５和０．０１）和亚急性期（Ｐ＜０．００５）心肌ＭＤＡ含量。以上资料表明，ＡＤＲ刺激产生的心肌脂质过氧化程度具有剂量和时间依赖性，而ＤＡＣ－树脂ＤＨＰ能明显降低急性期和亚急性期ＡＤＲ刺激产生自由基导致心肌膜结构脂质过氧化的程度。作者等认为本实验资料显示ＤＨＰ的同步应用能减轻ＡＤＲ所致的心肌急性期和亚急性期的损害程度，并有望于今后临床试用以提高ＡＤＲ的应用剂量和降低其毒性。     

Association of macromolecular prodrugs consisting of adriamycin bound to poly(L-glutamic acid)

Soluble macromolecular conjugates for the controlled delivery of the strongly hydrophobic antitumor drug adriamycin (ADR) were prepared. The association behaviour of two types of these amphiphilic conjugates consisting of ADR bound to poly(L -glutamic acid) (PGA) in aqueous solution was investigated using absorbance and fluorescence spectroscopy as well as GPC and lowangle laser light scattering (LALLS) measurements. ADR was bound via the aminoribosyl moiety either directly with PGA side-chain groups or via oligopeptide spacer groups. UV/VIS, GPC and LALLS data showed that in buffer solution both ADR conjugates associate intermolecularly. The data of the directly bound ADR conjugates are consistent with the presence of multimers of different degrees of association in equilibrium with single polymer chains. In contrast, spacer-containing ADR conjugates associate to give stable uniform multimers. UV/VIS and fluorescence spectroscopy performed at very low conjugate concentration show that polymer-bound ADR residues associate intramolecularly as well. The degree of intra- and intermolecular association of the conjugate-bound ADR molecules depends on the type of conjugate, ADR load and conjugate concentration as well as on ionic strength of the solvent, the presence of organic cosolvents and temperature. The data indicate that hydrophobic domains in spacer-containing conjugates are more stable compared with directly bound conjugates, probably due to enhanced flexibility and the presence of hydrophobic leucine residues. It is concluded that spacer-containing conjugates of ADR may have a potential for effective drug delivery under in vivo conditions due to their solution properties in addition to the biodegradability of the drug-polymer bond.     

Unerwünschte Arzneimittelwirkungen

Adverse drug reactions (ADR) occur in about 5% of all pharmacologically treated patients. Between 2% and 20% of all hospital admissions are caused by ADR, and approximately 10% of all hospitalized patients experience ADR during their hospital stay. Several thousand patients die due to ADR in Germany each year. ADR-associated drugs come predominantly from the class of non-steroidal antiinflammatory drugs, anticoagulants, acetylsalicylic acid and cardiovascular drugs. Most ADR cases present as gastrointestinal bleeding and adverse cardiovascular effects. Apart from this, one or more drugs are withdrawn from the market each year because of unwanted but mostly rare side effects. In recent years the most prominent cases were rofecoxib, cisapride and cerivastatin. Physicians in Germany are obliged to report ADR. A substantial proportion of ADR, however, is not reported because it is deemed to be either too well known or the association between the drug and the adverse effect is too doubtful. In some cases, histopathological findings are needed to determine the diagnosis of ADR. Accordingly, physicians should inform the pathologist whether an ADR is suspected and which drugs may be responsible.