他克莫司的不良反应

本文综述近几年在国内报道的他克莫司的药物不良反应,为更合理使用该药提供参考。     

他克莫司联合氟康唑治疗对他克莫司血药浓度的影响

目的:考查器官移植术后免疫抑制剂他克莫司与抗真菌药氟康唑联合应用对前者血药浓度的影响. 方法:对2004年9月-12月本院器官移植患者口服他克莫司同时口服或注射氟康唑的病例共计72例,除去32例氟康唑治疗不足1个疗程(7d)者,对40例患者的他克莫司血药浓度进行分析.送检的他克莫司血样用微粒子酶免疫法(MEIA法)进行血药浓度监测. 结果:在纳入研究的40例患者中,联合他克莫司口服(35例)或静脉输注(5例)氟康唑后,他克莫司第1日的血浆谷浓度分别升高为联合用药前的1.9倍和2.2倍,到第4日时他克莫司的给药剂量分别下降为联合用药前的67.3% 和70%. 结论:在移植术后早期,他克莫司联合氟康唑治疗可使他克莫司血浆谷浓度升高,应及时对他克莫司的剂量做出调整,避免因药物浓度的过高或过低产生毒性反应或引起排斥反应.     

他克莫司诱发移植后新发糖尿病高于环孢素A的机制研究进展

目的:综述近年来国内外学者对环孢素A和他克莫司诱发移植后新发糖尿病的机制研究,为临床合理用药提供依据。方法:检索国内外相关文献,进行整理和综合分析。结果:NODAT(new-onset diabetes after transplantation)即移植后新发糖尿病,也称PTDM(post-transplant diabetes mellitus),是器官移植患者常见、严重的并发症。NODAT发病的危险因素包括年龄、性别、高剂量类固醇、体重指数、家族史和免疫抑制剂,其中免疫抑制剂的使用是发病的高危因素。环孢素A和他克莫司是两种主要的免疫抑制剂,应用免疫抑制剂可以减少移植后急性排斥反应的发生率,提高患者的生存率,但使用免疫抑制剂会诱发NODAT,他克莫司导致NODAT发生率高于环孢素A,具体机制目前尚无定论。结论:临床医生可以根据他克莫司导致NODAT发生率高于环孢素A的机制,制定合理的给药方案。     

他克莫司的临床应用

他克莫司（tacrolimus，FK506）系从放射花线菌（steptomyces tsukubaensis）的发酵液中提取的大环内酯类抗生素，是第二代免疫抑制药的代表性药物，广泛用于器官移植的抗排斥反应，具有药效强、使用剂量低、器官存活率高、急性排斥反应发生率低等特点。临床上已作为预防排斥反应的主要药物之一。许多实验证实，他克莫司在体内和体外抑制淋巴细胞活性的能力比环孢素强10～100倍，且应用其防止排斥反应的有效剂量不到环孢素的1／10～1／100。     

他克莫司的临床研究进展

目的:介绍他克莫司的临床应用和实验研究进展.方法:查阅国内近10年正式发表的有关文献,进行综合分析.结果与结论:他克莫司除了用于器官移植的抗排异反应外,还有许多新的临床应用和实验研究报道.     

他克莫司的工业化研究

日本藤泽公司通过对他克莫司产生菌筑波链霉菌的选育,发酵条件优化,提取方法改良,以及建立简单、快速、可信度高的ＨＰＬＣ定量分析方法,顺利实现他克莫司的工业化生产,产率比原始菌株和原始发酵条件提高了３００倍,产物的异构化得到控制,产品纯度达到９９％以上。     

他克莫司的研究概况

目的综述近年来他克莫司的研究进展。方法以已有国内外材料为基础,进行分析和归纳。结果目前他克莫司的临床应用主要是应用在器官移植、免疫系统疾病。结论他克莫司在临床的应用有着广阔的前景。     

Severe prolonged tacrolimus overdose with minimal consequences

A 59-year-old man inadvertently received a 10-fold increase in his twice-daily oral dose of tacrolimus 1 mg that resulted in trough blood levels above 90 ng/ml for over a week. The patient had end-stage renal disease secondary to diabetes mellitus and had received a kidney transplant from his daughter 3 months earlier. Despite the numerous adverse effects commonly reported with tacrolimus, such as mild nephrotoxicity, nausea, tremors, and elevated liver enzyme levels, our patient's acute but prolonged overdose resulted in minimal signs and symptoms of toxicity. Nevertheless, education regarding the importance of accurate dosing, close monitoring, potential drug interactions, and the various capsule colors should be provided to all patients who receive tacrolimus, as well as their physicians, nurses, and pharmacists, in order to prevent as many errors as possible.     

他克莫司致可逆性室间隔肥厚

1例52岁女性患者因重症再生障碍性贫血行异基因造血干细胞移植术,术后服用环孢素预防移植物抗宿主病。2个月后因肾功能不全,换用他克莫司0.5~1.5 mg,2次/d口服,其血药谷浓度为2.4~7.2μg/L。此后患者逐渐出现气短、疲乏,夜间不能平卧等症状,服用他克莫司50 d后心脏超声检查示室间隔增厚（13 mm）。停用他克莫司,换用西罗莫司和吗替麦考酚酯胶囊后上述症状逐渐好转,20 d后心脏超声检查示室间隔厚度为10 mm。     

一例他克莫司引起血糖升高的用药分析

在临床工作中药师发现患者因膜性肾病使用他克莫司,引起继发性糖尿病1例,通过查阅文献对于患者此次出现血糖升高的机制和治疗策略展开讨论,指导患者正确使用降糖药物,患者目前血糖控制良好。临床工作中应重视他克莫司诱发的继发性糖尿病,正确认识并合理使用降糖药物。     

他克莫司引起继发性糖尿病的临床转归和药学监护

目的:对2例他克莫司(FK506)引起的继发性糖尿病(PTDM)患者进行随访并总结此类患者药学监护要点。方法:检索近年来国内外PTDM相关文献,指导患者正确使用降糖药物,进行规律血糖监测并复查糖代谢相关指标。结果:PTDM的发生机制类似于2型糖尿病,但其具有显著特点:发生PTDM多于移植后30～60d;随着移植时间的延长,胰岛素用量会较前显著减少,甚至停用;降糖策略应以胰岛素治疗为主。2例患者血糖水平较PTDM诊断初期均明显改善,降糖药物剂量明显减少。第1例患者在治疗过程中未发生严重低血糖,并在1年后PTDM临床缓解,血清C肽检查示胰岛细胞功能恢复良好;第2例患者发生PTDM后饮食控制不严格,血糖控制不达标,目前仍使用胰岛素控制血糖。结论:应重视他克莫司引起的PTDM,正确认识PTDM并指导患者规律监测血糖和合理使用降糖药物,防止发生低血糖。     

他克莫司致移植肾功能异常1例

他克莫司(tacmlimus)作为一种强有力的新型免疫抑制剂，1999年才开始应用于我国器官移植的临床实践中。国内有关他克莫司致移植肾功能异常的报告尚少，我们诊治一例，报告如下。     

他克莫司致儿童急性胰腺炎一例

1例3岁患儿因原发性肾病综合征口服他克莫司治疗,用药近16个月后出现阵发性剧烈腹痛,腹部超声示胰腺弥漫性肿大,诊断为急性胰腺炎。停用他克莫司,予生长抑素、醋酸奥曲肽等治疗,10 d后腹痛好转,复查腹部超声胰腺大小正常。     

Survival from coma induced by an intentional 36-g overdose of extended-release quetiapine

Quetiapine is a second-generation antipsychotic drug approved for the treatment of bipolar disorders and schizophrenia. Acute quetiapine overdose is rare, and quetiapine has long been thought to be safer than other antipsychotics. Nevertheless, as reported in the literature, the severity of the effect of quetiapine overdose has not been associated with a high serum concentration of the drug or with the reported ingested dose. In this article, we report a case of survival from coma induced by a massive extended-release (XR) quetiapine ingestion at a dose greater than reported in some previous fatal cases. A 34-year-old woman with chronic schizophrenia ingested 36?g of quetiapine fumarate XR for attempted suicide. She was initially lethargic, but her clinical conditions rapidly deteriorated and she collapsed unconscious. The woman was taken to the nearest hospital, where the medical emergency team found her in deep coma with response only to deep painful stimuli (Glasgow Coma Scale 9). An endotracheal tube was inserted for airway protection, and the patient was transferred to a critical care area for ventilatory support and maintenance of hydration status and electrolytic balance. Spontaneous breathing was restored in approximately 36 hours, and a few days later, she was discharged without reporting clinical complications. This is the first case of coma induced by an intentional 36-g overdose of quetiapine XR. Given the widespread use of quetiapine and the lack of information about its toxicity in overdose, this case report reinforces the importance of closely monitoring patients taking quetiapine and helps to better define the safety of this drug.