痹克颗粒致药物性肝损伤1例

1例47岁男性患者,因“痛风”发作,自行服用痹克颗粒(10 g, po, tid)治疗。服药后约10 d,出现“全身皮肤黄染、巩膜黄染”入院治疗。入院当日肝功能示总胆红素40μmol·L^-1,非结合胆红素14.2μmol·L^-1,碱性磷酸酶167.1 U·L^-1,总胆汁酸70.1μmol·L^-1,谷丙转氨酶374.4 U·L^-1,谷氨酰转肽酶645.8 U·L^-1,谷草转氨酶291.3 U·L^-1。考虑痹克颗粒致药品不良反应,停药保肝治疗1月余后,患者肝功恢复正常。     

不稳定心绞痛患者PCI术后出现肝损伤病例分析

目的探讨临床药师在合理用药中的作用。方法临床药师通过参与1例疑似药物性肝损伤(DILI)的病例分析,协助临床医师评价药物性肝损伤的可能性,根据病情变化及时调整用药方案,提供个体化的药学服务。结果 DILI虽然内涵清晰,概念明确,但由于患者及药物等因素的复杂多变,在很多情况下DILI难以准确判断;其临床诊断既需要考虑患者疾病状况、用药情况,甚至生活习惯,又要结合患者肝、肾功能相关指标,所用药物特性等多因素综合评判。结论临床药师应充分发挥在药物药理作用、代谢、不良反应等方面的专业优势,为保证患者药物治疗的安全性和有效性提供有力保障。在引发DILI药物难以准确判断的情况下,明确具体诱发药物并非第一要务;重要的是及时停用可疑药物及对症处理,改善患者预后;适时为患者提供DILI事前预防、事后合理的药学监护等个体化药学服务。     

异甘草酸镁治疗抗结核药物性肝损害的效果分析

目的 探讨异甘草酸镁治疗抗结核药物性肝损害的临床效果.方法 选择本院2012年8月～2013年8月收治的45例抗结核药物性肝损害患者为研究对象,随机分为观察组（23例）和对照组（22例）,对照组给予常规对症支持治疗,观察组在对照组的基础上给予异甘草酸镁治疗,对比观察两组患者的临床治疗效果.结果 两组患者治疗后肝功能各项指标均优于治疗前,且观察组较对照组改善更明显,差异有统计学意义（P＜0.05）.观察组优良率为91.30％（21/23）,明显高于对照组的63.64％（14/22）,差异有统计学意义（P＜0.05）.观察组不良反应发生率为8.70％（2/23）,对照组不良反应发生率为9.09％（2/22）,两组差异无统计学意义（P＞0.05）.结论 异甘草酸镁治疗抗结核药物性肝损害的临床效果显著,且药物安全性高,值得临床广泛推广.     

硫普罗宁治疗抗结核药物所致肝损害的效果观察

目的探讨硫普罗宁治疗抗结核药物所致肝损害的效果。方法选取本院收治的抗结核药物性肝损害患者130例,随机分为两组,分别行常规治疗与硫普罗宁注射液治疗,对比两组临床效果与安全性。结果观察组患者治愈率与总有效率高于对照组,肝功能检测显示丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBiL）、谷氨酰转肽酶（γ-GT）、AST／ALT均显著优于对照组,两组患者均无严重不良反应发生。结论硫普罗宁治疗抗结核药物性肝损害效果显著,能有效改善肝功能,减轻临床症状,且安全性较好,适合临床推广。     

哌拉西林钠他唑巴坦钠致多发伤患者发热并急性肝损伤1例

哌拉西林是一种广谱青霉素类抗生素,当与β-内酰胺酶抑制剂他唑巴坦联用时用于治疗敏感菌所致的中度至重度感染性疾病,常见的不良反应有过敏、皮疹、胃肠道反应等,亦可致发热并药物性肝损伤,但导致发热并急性肝损伤的病例罕见。本文报道1例患者应用哌拉西林钠他唑巴坦钠时出现的发热并急性肝损伤的病例,目的是能引起临床医生的关注,并为早发现、早诊断、早干预提供参考。     

1例蒲公英致化疗患者药物性肝损伤的药学监护实践与分析

目的 探讨药学监护在1例化疗患者使用中药蒲公英导致药物性肝损伤的诱因判断及相应处置过程中的作用.方法 通过药学监护发现1例化疗患者发生药物性肝损伤,利用药学相关知识与临床实践相结合,对患者出现不良反应的原因进行判断、干预和用药建议.结果 医生采纳药师建议,停用蒲公英,患者不良反应情况得到改善,顺利完成后续治疗.结论 药...     

国内外药品不良反应救济制度的探讨

目的：探索建立我国药品不良反应救济制度的方法。方法：分析我国现阶段开展药品不良反应救济工作面临的问题与挑战,介绍日本．德国．瑞典以及台湾的药品不良反应救济制度．并在此基础上．对我国制定以及完善相应制度提出初步设想。结果和结论：我国可借鉴国外药品不良反应救济方面的成功经验．结合我国国情．探索并制订出我国自己的药品不良反应救济制度,以保障患者的权益。     

从新实施的《侵权责任法》看我国药品不良反应的法律救济

目的：为建立我国药品不良反应的法律救济制度提供参考。方法：通过界定药品不良反应的定义,分析新实施的《侵权责任法》的严格责任原则,以及介绍日本药品不良反应损害救济制度．探讨建立我国药品不良反应损害救济制度的意义及方法。结果及结论：我国药品不良反应损害的法律救济制度应尽快建立和完善。     

急性药物性肝损伤的临床研究

目的 对305例住院诊断急性药物性肝损伤病例进行分型判断和关联性评价,探讨病因,为临床医生提供参考。方法 诊断急性药物性肝损伤305例,根据药物性肝损伤因果关系评价表(RUCAM)对病例进行分型和量化评分,列出可疑用药,评价其与肝损伤的关联程度。结果 305例急性药物性肝损伤病例,肝细胞型221例(72.5%),胆汁淤积型36例(11.8%),混合型48例(15.7%);RUCAM评分大于8分(非常可能)29例(9.5%),6～8分(很可能)181例(59.9%),3～5分(可能)86例(28.2%),1～2分(不大可能)8例(2.6%),小于1分(无关)1例(0.3%);中草药占肝损伤可疑用药的首位(47.5%),其中何首乌是导致肝毒性的可疑用药(6.9%)。结论 RUCAM评分有助于可疑药物与肝损伤的关联性评价,但仍有不足,中草药致肝损伤比例增加,何首乌药物肝毒性问题需要重视。     

Development of a cell-based assay system considering drug metabolism and immune- and inflammatory-related factors for the risk assessment of drug-induced liver injury

Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical pharmacotherapy. However, prediction of DILI is difficult because the underlying mechanisms are not fully understood. To establish a novel cell-based screening system to suggest drugs with hepatotoxic potential in preclinical drug development, comprehensive gene expression analyses during in vivo DILI are necessary. Using in vivo mouse DILI models and 4 sets of hepatotoxic positive and non-hepatotoxic drugs, we found that the hepatic mRNA levels of S100A8; S100A9; “NATCH, LRR, and pyrin domain-containing protein 3” (NALP3); interleukin (IL)-1β; and the receptor for advanced glycation endproducts (RAGE) were commonly increased in hepatotoxic drug-administered mice compared to non-hepatotoxic drug-administered mice. To clarify whether these 5 in vivo biomarkers can be applied to a cell-based screening system, we adapted human liver microsomes (HLM) in the presence of NADPH to assess the metabolic activation reaction, and we also adapted human monocytic leukemia cells HL-60, K562, KG-1 and THP-1 to assess the effects on mRNA expression of immune- and inflammatory-related factors. We investigated 30 clinical drugs with different safety profiles with regard to DILI and found that the total sum score of gene expression levels of S100A8, S100A9, RAGE, NALP3 and IL-1β mRNA in HL-60 or K562 cells incubated with HLM, could identify drugs at high risk for hepatotoxicity. We proposed the use of the total sum score of gene expression level for assessing metabolic activation by drug-metabolizing enzymes and immune- and inflammatory-related factors for the risk assessment of DILI in preclinical drug development.     

Mechanistic studies of PEG-asparaginase-induced liver injury and hepatic steatosis in mice

PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis, β-oxidation, very low-density lipoprotein (VLDL) secretion, and white adipose tissue (WAT) lipolysis were determined. Mice developed hepatic steatosis after PEG-ASNase, which associated with increases in bilirubin, ALT, and AST. The hepatic genes Ppara, Lcad/Mcad, Hadhb, Apob100, and Mttp were upregulated, and Srebp-1c and Fas were downregulated after PEG-ASNase. Increased plasma NEFA, WAT loss, and adipose tissue lipolysis were also observed after PEG-ASNase. Furthermore, we found that PEG-ASNase-induced liver injury was exacerbated in obese and aged mice, consistent with clinical studies of ASNase-induced liver injury. Our data suggest that PEG-ASNase-induced liver injury is due to drug-induced lipolysis and lipid redistribution to the liver.     

利用医院信息系统监测分析药物性肝损伤

目的：研究利用医院信息系统监测分析药物性肝损伤的特点。方法：从医院信息系统数据库中提取2011年9月20-30日间丙氨酸氨基转移酶、门冬氨酸氨基转移酶、总胆红素、结合胆红素、碱性磷酸酶和γ-谷氨酰转移酶异常的住院患者资料,进行回顾性分析。结果：可能发生药物性肝损伤的有147例,主要分型为肝细胞性肝损伤。涉及11个科室、13类药物,居首位的是抗菌药。结论：本方法可有效挖掘药物性肝损伤发生的信息,使用计算机自动监测预警药品不良反应有着广泛的应用前景。     

儿童与成年患者药物性肝损伤临床特征比较

目的：分析比较儿童与成年患者药物性肝损伤（ DILI）的临床特征方法以“药物性肝损伤”为检索词,检索2002年2月至2011年6月首都医科大学附属北京佑安医院病案管理中心的全部病历,将患者中≤14岁者纳入儿童组,≥15岁者纳入成年组。收集2组患者的病历资料进行回顾性分析,主要分析指标为用药情况、临床表现以及DILI的临床和病理分型。结果导致儿童组DILI的主要药物为抗菌药（13例,42%）、中药（9例,29%）和解热镇痛药（6例,19%）。导致成年组DILI的主要药物为中药（79例,69%）、解热镇痛药（12例,11%）和抗菌药（8例,7%）。儿童组26例（84%）、成年组114例（100%）分别在用药3-90 d[平均（18±15）d]和5-90 d[平均（30±20）d]后出现乏力、食欲减退、厌油、恶心、呕吐和尿液变黄,部分患者出现发热、皮疹及嗜酸粒细胞计数升高。实验室检查显示,2组患者血清丙氨酸转氨酶（ ALT）、天冬氨酸转氨酶（ AST）及谷氨酰转肽酶（GGT）水平差异无统计学意义,但儿童组碱性磷酸酶（ALP）水平明显高于高于成年组（P〈0.05）。儿童组31例患者中混合型肝损伤15例（48.4%）,肝细胞型和胆汁淤积型各8例（各25.8%）;成年组114例患者中肝细胞型肝损伤69例（60.5%）,混合型26例（22.8%）,胆汁淤积型19例（16.7%）。儿童组混合型肝损伤占比明显高于而肝细胞型肝损伤占比明显低于成年组（均 P 〈0.01）。出现DILI症状后,2组患者均立即停用有关药物,并给予保肝降酶及对症治疗。成年组所有患者与儿童组27例患儿好转出院,儿童组原发疾病恶化2例,因肝功能衰竭自行出院和死亡各1例。结论儿童和成人DILI的主要致病药物不同,前者以抗菌药为主,后者以中药为主。儿童DILI分型以混合型为主,成人则以肝细胞型为主。儿童使用抗菌药、成人使用中药时?     

保肝药物联合应用治疗化疗相关性药物肝损害的临床疗效观察

目的 探讨异甘草酸镁联合还原型谷胱甘肽对化疗引起的药物性肝损害的临床疗效.方法 采用单中心,随机分组、前瞻性研究的方法,将研究对象分为异甘草酸镁单药组(A组)、还原型谷胱甘肽单药组(B组)和联合用药组(C组),观察治疗2周后,三组患者血ALT、AST变化情况.结果 入选病例81例,均可评价疗效.在治疗结束后,A、B、C三组ALT水平分别为(73.64±19.28)U/L、(76.46±15.34)U/L、(56.80±17.33) U/L,显著低于(P<0.05)治疗前水平的(125.35±22.63)U/L、(122.22±21.69) U/L、(130.38±21.97)U/L;AST水平分别为(79.88±20.15)U/L、(80.48±15.72)U/L、(61.97±16.63) U/L,显著低于(P<0.05)治疗前水平的(140.37±20.15)U/L、(138.21±25.61) U/L、(147.59±24.38)U/L;三组ALT、AST下降幅度分别为(45.98±10.81)U/L、(40.76±13.57)U/L、(73.63±13.01)U/L和(60.56±13.88)U/L、(57.46±17.16) U/L、(84.96±15.59)U/L,两两比较,联合用药组与单药组(C组与A组、C组与B组)间有统计学差异(P<0.05),单药组(A组与B组)间无统计学差异(P>0.05).结论 与单一用药相比,异甘草酸镁联合还原型谷胱甘肽可显著降低化疗药物性肝损害患者的血ALT、AST水平.     

482例药品不良反应报告相关因素分析与对策

目的：分析宁德市医院药品不良反应（ADR）发生的相关因素特点及规律,为临床合理用药提供对策。方法：对我院2009—2011年收集到的482例ADR报告进行统计分析。结果：482例ADR报告中共涉及药品166种,男性发生率（265例,占54.98%）略高于女性（217例,占45.02%）;60岁以上患者发生ADR的比例最高（144例,占29.87%）;静脉滴注给药途径最易引发ADR（295例,占59.48%）;抗感染药引发的ADR例数最多（197例,占37.03%）;ADR累及器官和（或）系统以皮肤及其附件损害最为常见（165例,占30.05%）;严重的ADR有16例（占3.32%）;所有ADR均治愈和好转。结论：ADR发生与多种因素有关。医疗机构应完善医、药、护合作的ADR监测体系,加强ADR监测,发挥临床药师用药监护作用,合理用药,减少或避免ADR的发生。     

新型冠状病毒肺炎患者肝损的原因分析

自2019年12月以来,新型冠状病毒(SARS-CoV-2)感染的肺炎(COVID-19)已对公共卫生造成重大威胁[1]。值得关注的是,除呼吸系统外,大量的COVID-19患者还表现出各种程度的肝损伤临床特征[2-3]。本文将初步探讨COVID-19患者肝损伤的原因。1基于文献分析COVID-19患者肝损伤原因Chen等[4]在99名COVID-19患者中,发现有43例患者出现了不同程度的肝功能损伤。     

Drug-induced attack of bronchial asthma in inpatients: a 20-year survey of the Comprehensive Hospital Drug Monitoring Programme on adverse drug reactions, Berne/St. Gallen

Epidemiological aspects of attacks of bronchial asthma related to drugs are prospectively studied in inpatients of three teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM)-programme. Results are based on 34 840 individual patients (among 48 005 consecutive admissions) in the years 1974–1993. Between 1974 and 1993, every patient admitted to any of the three medical clinics in the CHDM programme was monitored for any suspicion of an adverse drug reaction (ADR); every drug exposure period during hospital stay was registered. Nineteen patients (0.05% of the 34 840 individual patients) had at least one attack of bronchial obstruction during hospitalisation, considered as probable or definite ADR. The frequency related to exposure periods in response to penicillins is 0.014%, to non-steroidal anti-inflammatories (NSAIDs) 0.014%, to acetyl salicylic acid (ASA) 0.018%, to paracetamol 0.008% and to β-adrenoceptor blockers 0.26%. Of the 12 patients reacting to a drug with an allergic or idiosyncrasy/intolerance type of bronchial obstruction, 7 had a history of bronchial asthma (extrinsic or intrinsic), and 3 had the diagnosis chronic obstructive pulmonary disease (COPD). A history of bronchial asthma or COPD is confirmed to be a risk factor for this particular ADR. Of the seven patients with a bronchial obstruction to β-adrenoceptor blockers, five were diagnosed with COPD, while two had neither COPD nor bronchial asthma. The relative risk for this pharmacological reaction in COPD patients was 96 (95% confidence interval 45–208) compared with non-COPD patients in the group of 3 244 exposed to β-adrenoceptor blockers. Received: 5 December 1996 / Accepted in revised form: 28 May 1997     

乌司他丁对原位肝移植术肺损伤的保护作用

目的:观察原位肝移植术(OLT)中肺损伤的程度,探讨乌司他丁(UTI)对OLT中肺损伤的保护作用.方法:40例择期行OLT手术患者随机分为UTI组和对照组各20例,UTI组(n=20)切皮后将UTI 100万单位加入100mL生理氯化钠溶液,持续静脉输注,之后每隔4 h重复使用.对照组(n=20)以等容量生理氯化钠溶液代替.于麻醉后切皮前、无肝前期120 min、无肝期30 min、新肝期10 min、新肝期60 min和术毕对肺顺应性、吸气阻力、呼气阻力、峰值压力和平台压力进行观察.结果:在新肝期10 min、新肝期60 min和术毕时,对照组的肺顺应性显著下降,吸气阻力、呼气阻力、峰值压力和平台压力显著升高(P<0.05).UTI组的吸气阻力、呼气阻力、峰值压力和平台压力值均明显低于对照组(P<0.05),而肺顺应性值明显高于对照组(P<0.05).结论:0LT过程造成肺损伤,UTI在OLT中对肺损伤有保护作用.