药物的不良反应

药物不良反应(Adverse Drug Reactions)是指在常用量情况下,药物或药物相互作用而发生的与防治目的无关的不利或有害反应,包括副作用、毒性作用、过敏反应、继发反应和特异性遗传素质等。按照分类,药物不良反应可以分为A型和B型两大类。A型不良反应(量变型异常)的特点是可以预测,通常与剂量有关,在人群中的发生率虽高,但死亡率低。B型不良反应(质变型异常)是与正常药理作用完全无关的一种异常反应,一般很难预测,常规的毒理学筛选     

抗结核药物的肝毒性

抗结核药物大多经肝脏代谢,因而对肝脏具有不同程度的损害,处理不当,严重者会危及患者的生命。充分认识这类药物对肝脏的毒性,对结核病的防治有着重要意义。1　异烟肼(雷米封,INH) 单用INH致肝脏毒性的发病率约为10％,多见于治疗的第10周内,大多数病例停药后可自行恢复。长期较大剂量     

常见抗结核药物的肝损害及其处理

抗结核药的广泛应用,对控制结核病流行起了划时代的作用.但每种抗结核药对肝脏都有影响.文献报告接受抗结核治疗者发生可逆性中度转氨酶升高的比例为15～30%[1,2,3].虽然其中大多不必中止治疗,但少数病例应及时停药,否则危及生命.因此,对抗结核药物肝损害的认识和处理是结核病化疗的一个重要问题.     

几类常用药物的肝毒性

药物的不良反应无疑是医务工作者在工作中经常面临的问题，而药源性肝病在药物常见不良反应中占相当比率。非甾体抗炎药、降压药、降糖药、抗惊厥药、降血脂药和抗精神失常药都是临床常用药物，让医生充分了解这些药物的肝毒性对于提高临床用药的安全性是非常重要的。     

环孢素所致的肝损害药物防治

环孢素易致肝损害如胆汁瘀积,肝坏死,肝纤维化,而临床使用环孢素往往剂量大,疗程长,使用环孢素同时必需合用护肝保肝类药物,是减轻或延缓肝损害的主要措施。本文主要介绍环孢素所致肝损害的表现和护肝药物的品种和作用机制。     

抗结核药物致肝损伤分析

结核病的化学疗法是控制结核病的首选且最有效的治疗方法,但抗结核药物存在着较多的毒副作用,其中最主要的是肝毒性（antituberculosis drug-induced hepatotoxicity,ATDH）,是导致化疗中断的主要原因之一。笔者通过对临床遇到的1例抗结核药物所致肝损伤进行分析,以了解抗结核药物ATDH的发病机制,选择合适的治疗方案,降低肝损伤的发生率。     

抗微生物药物的肝脏毒性

抗微生物药物的应用可引起各种各样的肝脏损害,范围从轻微、无症状的肝生化指标异常到威胁生命的暴发性肝脏衰竭,其机制不十分清楚,但反应一般是不可预测性和特异体质性的。在大多数病例中,抗微生物药物引起的肝毒性是自限性的,停药恢复。但随着慢性病毒和细菌感染的日益流行,常常需要长期的多药联合治疗,因此,早期认识和合理处理肝脏损害显得日益重要。     

利用医院集中监测药物不良反应管理系统适时监测药物性肝损害

目的 :研究利用医院集中监测药物不良反应管理系统监测药物性肝损害的方法。方法 :应用自制程序 ,从医院住院患者数据库中提取2001年12月～2002年2月丙氨酸氨基转移酶、门冬氨酸氨基转移酶和总胆红素异常的住院患者资料 ,并进行回顾性与适时性分析。结果 :可能涉及药物不良反应的有50例 ,相关药物有11类、30种 ;属不合理用药的有11例 ,相关药物有10种。结论 :通过这种方法可及时获得药物性肝损害发生的信息 ,同时这也为医院集中开展药物不良反应监测提供了一种新的思路。     

696例药物性肝损害药物的临床分析

近年来随着临床药物种类的迅速增多和药物治疗的增加,非处方药物范围的不断扩大及患者自行服药的机率增加,药物性肝损害的发生率正在逐年增多[1]。我们研究了我院1994年至2006年住院的696例药物性肝损害患者的损肝药物、药物变迁及年发病率,并总结分析其临床特点。     

胺碘酮静脉滴注致急性肝损害15例临床分析

目的:分析静脉滴注胺碘酮致急性肝损害的原因和机制。方法:对我院2005年发生的2例以及1988-2005年国内外文献报道的13例静脉滴注胺碘酮后出现急性肝损害患者的基本情况、基础疾病、应用胺碘酮指征、肝功能损害特点、合并用药情况以及转归等进行分析。结果:急性肝损害前静脉滴注胺碘酮剂量为200～1740(1073±413)mg,用药至发生肝损害的时间为12～48(24.0±7.9)h,天冬氨酸氨基转移酶峰值为450～17471(5283±5217)U/L,丙氨酸氨基转移酶峰值为759～12426(4074±3508)U/L。停药后1d肝功能均开始好转,其中7例改为口服胺碘酮,肝功能继续趋于好转。结论:胺碘酮静脉滴注可导致急性肝损害,助溶剂聚山梨醇酯80可能是引起急性肝损害的原因。     

药源性晕厥及其防治

晕厥系指一过性、广泛性脑供血不足导致的短暂意识丧失状态。晕厥可由多种原因引致,如心血管疾病、低血糖以及药物等,药物引起的晕厥占2%～9%。药源性晕厥可分为4种类型:心源性晕厥、直立性低血压性晕厥、血管抑制性晕厥,其他原因晕厥,其临床表现为眩晕、心慌、恶心、出汗、四肢无力、意识丧失及跌倒等。引起晕厥的药物以心血管系统药物、解热镇痛药物和抗菌药物为最多见。药源性晕厥的治疗通常为停药和使患者平卧。但药物引起的心源性晕厥的治疗方法因患者病情而有所不同。预防药源性晕厥的主要措施为:合理选择药物和剂量,控制静脉用药的浓度和速度,谨慎药物联用以及加强用药监测等。     

162例药物性肝损害不良反应/事件报告分析

目的探讨药物性肝损害不良反应/事件发生的临床特点和规律,为临床合理用药提供参考。方法采用回顾性研究的方法,从安徽省2012年药品不良反应/事件数据库中筛选出162例药物性肝损害病例,并行整理、统计与分析。结果统计数据显示药物性肝损害中,年龄≥60岁的老年患者发生率最高,占35.80%。涉及10大类药物,西药引起例次较多,占89.20%,其中以抗肿瘤药所占比重最大,其次为抗菌药、质子泵抑制剂和抗脑血管病药;中成药以中药注射剂引起例次最多,占8.92%。发生药物性肝损害的最常见给药途径是静脉滴注,占71.83%。肝损害发生时间差异较大,最短的1天,最长的175天。临床表现与实验室检查无明显特异性,大部分病例在停药和对症治疗后好转。结论临床医务人员应该提高对药物性肝损害的认识,一旦确诊为药物性肝损害,积极采取对症治疗,同时要加强不良反应监测,提高合理用药水平。     

Adverse drug reactions in hospitalized patients: An operational procedure to improve reporting and investigate underreporting

Background — Adverse event (AE) underreporting is a serious obstacle to drug safety monitoring in hospitalized patients, and it is necessary to find new approaches for improving the situation. The aim of the present study was to try to improve reporting and to evaluate the difference between actual and expected reporting. Methods — The drug surveillance programme was implemented in a 72-bed internal medicine ward. A simple algorithm was printed on each page of the progress notes of the patients' medical record, which the physicians were asked to use in choosing the AEs to be reported to the drug surveillance system. The actual reporting was evaluated for a period of 12 months (1203 patients). Using the same algorithm, two reviewing doctors evaluated expected reporting by analysing all of the AEs deduced from the records of 120 randomly selected patients. Results — Actual reporting: over a period of 12 months, the doctors reported 89 AEs (7.4 per 100 patients), whereas no event had been reported to the national drug surveillance system in the twelve months preceding the introduction of the project. Actual versus expected reporting: in 120 randomly selected patients, 22 AEs were considered by the reviewers as constituting the expected reporting; nine were actually reported. Conclusions — The described drug surveillance programme led to a substantial improvement in adverse event reporting, although a considerable difference still remains between expected and actual reporting.     

Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis.

Kupffer cells are resident macrophages of the liver and play an important role in its normal physiology and homeostasis as well as participating in the acute and chronic responses of the liver to toxic compounds. Activation of Kupffer cells directly or indirectly by toxic agents results in the release of an array of inflammatory mediators, growth factors, and reactive oxygen species. This activation appears to modulate acute hepatocyte injury as well as chronic liver responses including hepatic cancer. Understanding the role Kupffer cells play in these diverse responses is key to understanding mechanisms of liver injury. Idiosyncratic drug-induced liver disease results in morbidity and mortality, impacting severely on the development of new pharmacological agents. Modulation of the response of Kupffer cells by drugs has been suggested as a cause for the idiosyncratic response. Similarly, liver damage seen in chronic ethanol consumption appears to be modulated by Kupffer cell activation. More recent evidence has noted a contributory role of Kupffer cell activation in the process of hepatic carcinogenesis. Several nongenotoxic carcinogens, for example, activate Kupffer cells resulting in the release of cytokines and/or reactive oxygen species that induce hepatocyte cell proliferation and may enhance clonal expansion of preneoplastic cells leading to neoplasia. Kupffer cells therefore appear to play a central role in the hepatic response to toxic and carcinogenic agents. Taken together, the data presented in this symposium illustrate to the toxicologist the central role played by Kupffer cells in mediating hepatotoxicity.     

头孢菌素致药源性血小板减少症35例的文献分析

目的探讨头孢菌素致药源性血小板减少症(DITP)的相关特征。方法通过中国知网、万方、维普3大数据库,检索头孢菌素致DITP个例文献,进行一般情况、感染疾病、头孢菌素种类、用药前后血小板(PLT)变化、骨髓穿刺和凝血检测结果、临床表现、PLT恢复时间、临床转归等内容进行统计分析。对首次发现DITP的PLT计数和停药前的PLT计数进行对比分析。结果30篇文献35例患者,男女之比为2:1,年龄均值(57.9±25.2)岁。涉及头孢菌素类药品14种,其中头孢哌酮类占48.6%。临床表现,无症状为51.4%,出血表现为48.6%。首次发现DITP时间为2min~11d间,其中≤1d、2d~4d、5d~7d和≥8d分别为39.4%、21.2%、27.3%和18.2%。首次检测停药为57.1%、第2次检测停药为37.1%、第3次检测停药为5.7%。首次发现DITP和停药前PLT计数的降低程度和检测值,均存在显著性差异(X²=8.231、P=0.004,t=3.878、P=0.000)。PLT恢复率97.1%、临床病死率2.9%。结论临床对头孢菌素所致的DITP普遍认识不足,早期识别DITP,对改善患者的预后具有重要的临床意义。     

Adverse drug reactions in liver cirrhosis

Summary Impaired liver function may increase susceptibility to drug toxicity. In a prospective drug surveillance study of 1280 patients the frequency of adverse drug reactions (ADR) was higher in 333 patients with clinical and/or histopathological evidence of liver cirrhosis than in 188 with other liver diseases (p<0.01) and than in 759 without liver disease (p<0.0001). The 128 cirrhotics had 339 events considered definitely or probably related to drug therapy by consensus of the monitoring team and the attending physicians. ADR were 93.8% dose-related, 11.2% were severe but only one was fatal. ADR were most commonly associated with diuretics (32.6% of patients administered the drugs), potassium salts (6.5%), antimicrobials (3.9%) and sedatives (3.5%). Most common manifestations were metabolic (62.6%), gastrointestinal (13.2%) and neurologic (11.9%). The frequency of ADR was higher in females (p<0.05), patients receiving more drugs (p<0.001), those with longer hospital stay (p<0.001) and those with ascites (p<0.0001), portal hypertension (p<0.0001), prior hepatic encephalopathy (p<0.02) or prolonged prothrombin time (p<0.0001). Adverse reactions were more common for drugs biotransformed greater than 50% by the liver (p<0.005). These findings show that ADR are more frequent in severe hepatic dysfunction.     

呼吸内科病房药物不良反应监察与评价

在呼吸内科病房进行了为期一年的药物不良反应（ＡＤＲｓ）集中监察。２３９例病人中５２例发生了７０次ＡＤＲｓ，ＡＤＲｓ的总发生率为２１．８％。ＡＤＲｓ的发生与病人的住院时间、用药种数及既往药物过敏史等因素密切相关。常见的ＡＤＲｓ为神经肌肉反应、各型皮疹、消化道反应或肝功损害。抗结核药物、抗生素、心血管药物等发生不良反应的频度较高。     

Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity

The advances in the drug development that allowed the replacement of many potentially hepatotoxic agents by safer alternatives have been out-weighed by the vast expansion of the total number of agents now available for use. Now, rare adverse reactions to several commonly prescribed medications contribute to the total burden of drug-induced liver injury. Studies involving well-characterised patients with diclofenac-induced hepatotoxicity indicate that multiple steps are involved in the development of liver injury. Individual susceptibility to idiosyncratic hepatotoxicity is determined by the interaction of metabolic and immunological factors. Immunomodulatory and anti-inflammatory cytokines, such as IL-10, may have a protective role in reducing drug-induced liver injury. Understanding the mechanisms of idiosyncratic hepatotoxicity may increase our ability to identify susceptible individuals and hence, prevent serious adverse reactions.     

利巴韦林致182例不良反应文献分析

目的:探讨利巴韦林所致不良反应的一般规律及其特点,为临床合理用药提供参考。方法:对国内医药期刊报道的182例利巴韦林的不良反应病例进行分类统计分析。结果:利巴韦林所致的不良反应与给药剂量无关,临床表现复杂多样,但主要表现为过敏反应,严重者可出现过敏性休克和血液系统方面的损害。结论:应重视利巴韦林不良反应的监测,以促进临床合理用药。