肾移植受者红细胞ITPA活性与硫唑嘌呤不良反应关系的研究

目的建立一种测定三磷酸肌苷焦磷酸酶(ITPA)活性的高效液相色谱法(HPLC),探讨ITPA活性与硫唑嘌呤(AZA)导致的不良反应的关系。方法应用新建立的高效液相色谱法测定110例肾移植患者红细胞ITPA活性,分析ITPA活性在发生了不良反应的患者与未发生不良反应的患者间的差异。结果110例患者红细胞ITPA活性范围为2.0～575.7U,平均为(373.4±148.3)U,ITPA活性在男性和女性患者间无差异(P>0.05)。将76例未发生不良反应的患者作为对照组,其平均ITPA活性为(391.1±140.5)U。10例发生了血液毒性和14例发生了肝脏毒性的患者平均ITPA活性与对照组患者比较无差异(P>0.05)。10例发生了胃肠紊乱的患者平均ITPA活性为(177.1±69.6)U,明显低于未发生不良反应的患者(P<0.05)。结论硫唑嘌呤所致的血液毒性和肝脏毒性与ITPA活性无明显相关性,硫唑嘌呤所致的胃肠紊乱与ITPA活性低下有关。ITPA活性测定对指导临床硫唑嘌呤的合理应用具有一定意义。     

肾移植受者硫嘌呤甲基转移酶基因多态性与硫唑嘌呤不良反应关系的研究

目的:探讨硫嘌呤甲基转移酶(thiopurine S-methyltransferase,TPMT)表型和基因多态性与硫唑嘌呤(AZA)所致不良反应的关系。方法:应用高效液相色谱法(HPLC)测定150例肾移植患者红细胞TPMT活性,采用等位基因特异性的PCR和限制性片断长度多态性的方法检测TPMT*2、*3A、*3B和*3C四种基因型,分析TPMT活性和基因多态性与AZA所致不良反应的关系。结果:30例(20%)患者由于发生了不良反应而停用AZA或减少了AZA的用量,其中12例患者发生了血液毒性,另外18例发生了肝脏毒性。将未发生不良反应的患者作为对照组,其红细胞TPMT活性范围为16.63~68.25 U,平均为(38.43±11.59)U。发生了血液毒性的患者红细胞TPMT活性平均为(24.16±9.84)U,明显低于未发生不良反应的患者(P=0.0003)。另外18例发生了肝脏毒性的患者TPMT活性离散度较大,与对照组比较差异无统计学意义(P=0.145)。本研究未发现TPMT活性缺乏者。共发现7例(4.7%)TPMT*3C杂合子患者,这7例患者均为TPMT中等活性13.04~19.21 U,平均为(...     

<Emphasis Type="Italic">TPMT</Emphasis> but not <Emphasis Type="Italic">ITPA</Emphasis> gene polymorphism influences the risk of azathioprine intolerance in renal transplant recipients

Purpose  Thiopurine drugs have to be withdrawn in 10–30% of cases due to side effects, and it has been presented that genetic factors may be responsible for some of reported toxicity cases. Among polymorphic enzymes of thiopurines’ metabolic pathway, thiopurine S-methyltransferase (TPMT) has been studied most extensively, and some recent studies point to inosine triphosphate pyrophosphohydrolase (ITPA) polymorphism as an additional toxicity risk factor. Methods  The aim of the current study was to evaluate an association between TPMT and ITPA gene polymorphisms and drug intolerance in a cohort of 157 renal transplant recipients treated with azathioprine (AZA). Each subject was genotyped for the presence of variant TPMT (*2, *3A, *3B, and *3C) and ITPA (94C>A and IVS2+21A>C) alleles. Results  Mean AZA dose, mean white-blood-cell count, and platelet count in the course of treatment were lower in carriers of variant TPMT alleles compared to patients with TPMT wild-type genotype. Leukocyte numbers fell below 4.0 × 10⁹/L in 41.2% of TPMT heterozygous renal transplant recipients, compared to only 18.0% of wild-type patients (P < 0.01). In contrast, ITPA genotype did not influence AZA dose, hematological parameters, or leucopenia risk. Conclusions  Our results suggest that routine genotyping of renal transplant recipients for TPMT variants may be useful in reducing the risk of AZA-related myelotoxicity, but there is not enough evidence to introduce ITPA testing into clinical practice.     

肾移植术后吗替麦考酚酯替换硫唑嘌呤的临床分析

目的 :观察肾移植后吗替麦考酚酯 (MMF)替换硫唑嘌呤 (Aza)的安全性及其临床效果。方法 :回顾分析16例由Aza转换为MMF患者的临床资料。4例因肝功能损害而改用MMF,7例肾功能损害 ,5例应患者要求而换用MMF。结果 :4例肝功能损害者肝功能均恢复正常 ,7例肾功能损害者2例逆转 ,4例肌酐 (SCr)下降但未能恢复正常 ,1例继续恶化恢复血液透析。2例不良反应包括原有贫血明显加重 ,1例腹泻。结论 :Aza可以安全替换为MMF。因环孢素 (CsA)加Aza引起肝功能损害者 ,换用MMF ,减少CsA用量 ,肝功能可望恢复。MMF对部分慢性排斥反应可能有效     

肾移植受者血药浓度监测与最佳浓度选择

目的:寻找环孢素A(CsA)在肾移植受者三联免疫抑制用药方案中的最佳浓度.方法:用特异荧光偏振免疫法测定82例患者全血环孢素A的浓度,比较不同剂量组(各41例)患者肾移植术后CsA浓度高低、急性排斥反应和毒性反应发生率以及移植患者的人/肾生存率.结果:高浓度组在1年内总的急性排斥反应发生率为16.8%,低浓度组为18.2%,两组间差异无显著性(P＞0.05),高低浓度组患者1年内毒性反应发生率分别为32.1%和16.4%(P＜0.01),人/肾生存率分别为85.2%/82.8%和92.1%/90.9%(P＜0.05).结论:实验结果表明,低浓度组并不增加急性排斥反应的发生率,但明显降低毒性反应发生率以及移植患者的人/肾死亡率.     

米卡芬净临床不良反应及合理用药

目的分析并探讨米卡芬净不良反应(ADR)发生的类型及特点,为临床安全、合理用药提供参考。方法检索国内外有关米卡芬净不良反应的病例报道,对其不良反应发生类型及特点进行分析和总结。结果米卡芬净的不良反应以皮疹、胃肠道反应及肝损害最为多见,另外可见心血管疾病、溶血及过敏反应等。结论鉴于米卡芬净可造成患者多个器官和系统的不良反应,医药人员在临床治疗过程中应加强不良反应的监测,减少和防止ADR的发生率,以确保患者的用药安全。     

779例药物不良反应报表分析

目的:了解药品不良反应(ADRs)在我院的发生情况及其给患者造成的危害。方法:对我院1999年1月～2005年12月收集到的779例ADRs报表进行统计分析。结果:涉及ADRs的药物共118个品种,其中抗感染药物居多,静脉给药是引起ADRs的主要给药途径,主要的ADRs类型为皮肤损害及全身性损害。结论:应重视临床药物不良反应的监测。     

我院136例中药不良反应分析

目的了解中药不良反应发生情况、特点及规律,为临床合理用药提供参考。方法采用回顾性研究方法,收集我院2002-2009年上报的136例中药不良反应报告表,对不良反应病例涉及的药物品种、给药途径、主要不良反应症状及转归等进行统计分析。结果我院136例中药不良反应发生率随年龄的增加而升高,其中60岁以上人群发生率最高,占36.76%。发生不良反应的药物剂型以注射剂(57.35%)和口服制剂为主。不良反应损害涉及皮肤、胃肠、中枢和外周神经、心血管等全身多器官、系统。结论应重视中药的不良反应,完善、充实药品上市后的再评价体系,加强中药各环节的监管,提高合理用药水平。     

Identification and functional analysis of two rare allelic variants of the thiopurine S-methyltransferase gene, TPMT*16 and TPMT*19

Human thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. TPMT is genetically polymorphic and is associated with large interindividual variations in thiopurine drug toxicity and therapeutic efficacy. During routine genotyping of patients with Crohn's disease, one novel missense mutation, 365A>C (TPMT*19, Lys(122)Thr), and a recently described missense mutation, 488G>A (TPMT*16, Arg(163)His), were identified in a Caucasian and a Moroccan patient, respectively. Using a heterologous yeast expression system, kinetic parameters (K(m) and V(max)) of the two variants with respect to 6-thioguanine S-methylation were determined and compared with those obtained with the wild-type enzyme. The Lys(122)Thr exchange did not significantly decrease the intrinsic clearance value (V(max)/K(m)) of the variant enzyme. In contrast, the Arg(163)His substitution significantly decreased the intrinsic clearance value by three-fold. The Arg(163) is located in a highly conserved region of the human TPMT protein and, as such, the Arg(163)His substitution is expected to result in a marked reduction of enzyme activity, as confirmed by the in vitro data. Phenotyping by measurement of red blood cell TPMT activity indicated that the patient heterozygous for the Lys(122)Thr mutation had normal TPMT activity, whereas the patient heterozygous for the Arg(163)His mutation was an intermediate methylator, which demonstrated a positive correlation between TPMT phenotyping and the in vitro data. The identification of a novel non-functional allele of the TPMT gene improves our knowledge of the genetic basis of interindividual variability in TPMT activity. These data further enhance the efficiency of genotyping methods to predict patients at risk of an inadequate response to thiopurine therapy.     

住院患者药品不良反应报告分析

目的:了解住院患者发生药品不良反应(ADRs)的情况。方法:按患者的年龄、性别、用药情况及ADRs的主要表现、严重程度等进行统计分析。结果:185例报表中,男性87例,女性98例,涉及药品82种,主要为抗感染药物(46.49%),其次为中药制剂(16.76%),ADRs主要表现是皮肤及附件损害,其次是循环系统、消化系统。结论:应加强对住院患者ADRs的监测工作,以保证用药安全性。     

文拉法辛所致不良反应国内研究概况

笔者汇总国内有关期刊发表的文拉法辛临床研究文献121篇,综合其不良反应发生情况。发现文拉法辛常见的不良反应有恶心、口干、头晕、食欲减退、失眠、头痛、便秘、乏力、血压升高、出汗、视物模糊、窦性心动过速、兴奋激越、排尿困难等。这些不良反应的临床表现多为轻、中度,患者能够耐受。     

257例药品不良反应报告分析

目的探索我院药品不良反应的发生规律和特点,为临床安全用药提供信息。方法采用回顾性分析方法,对257例药品不良反应报告进行统计分析。结果 257例报告中,发生不良反应的患者性别比例无明显差异;50岁以上患者的ADR发生率高于其他年龄段;发生不良反应的药品以抗菌药物最多见;不良反应类型以皮肤及其附件损害最多见。结论应加强药品不良反应监测,将抗菌药物作为不良反应监测的重点,以提高临床安全用药意识、确保患者用药安全。     

药品不良反应报告300例分析

目的调查药物不良反应（ADR）的发生情况,促进临床合理用药。方法对300例药物不良反应（ADR）报告分别从患者年龄、性别、给药途径、涉及药物种类及临床表现等方面进行分析和统计。结果300例ADR报告中涉及药品9类,其中抗感染药物占首位（23．67％）。主要的ADR类型为皮肤及附件损害（41．67％）,其次为免疫系统损害（23．67％）。结论应重视ADR监测工作,促进临床合理用药。     

我院108例药品不良反应报告分析

目的 了解本院药品不良反应（ADR）发生的特点和规律。方法 选取108例ADR报告,按患者的性别、年龄、给药途径、累及的器官及临床表现等进行统计分析。结果 108例ADR报告中,男女比例为1：1.84;静脉引起的ADR最多,占90.74%;涉及药品34种;ADR主要是由抗菌药物和中药注射剂引起的,分别占40.74%和33.33%;ADR的临床表现主要为皮肤及其附件的损害为主,占39.29%。结论 加强和重视ADR的监测工作,规范临床用药,减少或避免不良反应的发生。     

药物不良反应的分析、预防与监测

药物不良反应是临床用药中常遇到的现象,成为危害人类健康的主要杀手,在我国引起了越来越多的关注和研究。本文对引起药物不良反应的原因进行了多方面的分析,同时提出了相应的预防措施,加强对药物不良反应的监测和防范,减少和避免药物不良反应的发生。     

药品不良反应240例报告分析

目的了解该院药物不良反应（ADR）发生的临床特点,为临床安全、合理用药提供参考。方法对该院2009年1月-2009年12月收集到的240例药品不良反应报告进行回顾性分析。结果 240例药品不良反应报告中男女之比1∶1.0339,60岁以上老年患者发生率较多,占30.00%;其中抗感染药物占首位（70.83%）,静脉给药方式为主要途经（76.25%）;临床表现以皮肤及其附件损害最常见（66.25%）。新的不良反应19例,其中严重的1例;严重的不良反应14例。结论应加强ADR的监测和ADR知识的宣传,避免或减少其重复发生,对新的、严重的不良反应应引起重视。     

The systems for monitoring adverse drug reactions in Hong Kong

Post-marketing surveillance is essential for providing additional safety information on drugs. In Hong Kong, a scheme to monitor ADRs was introduced in October 1986. It relies on voluntary reporting by hospital doctors and general practitioners of suspected ADRs. There appeared to be gross under-reporting as only 68 reports were received between 1986 to 1991. Although hospital-based studies have provided us with information on the pattern of and the risk factors for ADRs, spontaneous reporting on a national scale remains the only feasible and inexpensive method for monitoring ADRs. In order to increase reporting, we hope to convince the medical profession in Hong Kong of the importance in reporting ADRs and to make it easier for them to report.     

Spontaneous reporting of adverse drug reactions to non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are the third most commonly prescribed group of drugs in Spain. We present here the profile of adverse drug reactions (ADRs) attributed to them and reported to the Spanish System of Pharmacovigilance (SSPV) between 1983 and 1991, together with a preliminary analysis of topical, slow-release (SR) and enteric-coated (EC) preparations.Out of 18 348 reports of ADRs included in the SSPV database, 1609 (8.8%) implicated an NSAID. NSAIDs ranked second after antibiotics (15.1% of all reports) among the most commonly implicated drugs. Half of the patients were more than 55 years old, and 60% were women.Diclofenac (364 reports), piroxicam (282), indomethacin (197), naproxen (155), and ketoprofen (137) were the most commonly implicated NSAIDs in reports of ADRs.The most commonly reported ADRs were gastrointestinal (39%), cutaneous (20%), and those affecting the central and peripheral nervous system (9%). Seven reactions had a fatal outcome, and 138 were considered life threatening. Forty-nine reports included previously undescribed ADRs.There were 98 reports describing ADRs attributed to topical NSAIDs; 5 of these described 11 general reactions, such as duodenal ulcer, gastrointestinal bleeding, diarrhoea, dyspnoea, facial oedema, aggravation of bronchospasm, and angioedema.One hundred and sixty-eight reports referred to SR and EC preparations. The ratio of gastrointestinal to non-gastrointestinal reactions to SR-EC diclofenac was higher in the case of SR-EC diclofenac than in the case of plain diclofenac (P=0.037); similarly, the ratio of CNS to non-CNS reactions to SR-EC indomethacin was also higher than the corresponding ratio with plain indomethacin (P=0.002). Although differential selective reporting of these preparations cannot be excluded, these results raise doubts about the relative safety of SR and EC preparations of NSAIDs in practice.     

我院2010年179例药品不良反应报告分析

目的了解我院药品不良反应（ADR）发生的特点。方法采用回顾性调查方法对我院2010年上报的179例ADR报表进行统计分析。结果儿童和老人的ADR发生率较高;静脉滴注引发ADR发生率最高,有146例（81．56％）;所涉及的药品以抗感染药居多,有99例（55．31％）,以头孢菌素类、青霉素类多见;新的、严重的ADR有3例（1．6％）。结论临床应重视ADR的发生。     

100例药品不良反应的统计分析

目的 分析药品不良反应的发生情况及相关因素,为临床合理用药提供科学依据.方法 采用回顾性分析,对100例药品不良反应报告进行统计和分析.结果 100例药品不良反应中,31岁以上的药品不良反应病例发生率相对比较高占87% 皮肤及其它附件的损害占30% 静脉途径给药引起的药品不良反应占82% 涉及药品不良反应的药物共150种,其中抗感染药占65%,其次是中药注射剂占10%.结论 药品不良反应的发生与多种因素有关,应重视药品不良反应的监测和报告工作,以减少或避免药品不良反应的发生,确保临床安全用药.