抗精神病药物致Q-T间期延长时电解质变化分析

目的：了解抗精神病药物致Q-T间期延长时电解质的变化。方法：收集自2012年1月～2013年12月在本院住院病人150例,服用各种抗精神病药物后一个月查心电图、血生化。结果：150例患者一个月后心电图正常者89例,Q-T间期延长者27例,其他异常者34例。27例Q-T间期延长中低钾12例,低钙4例,低钾、低钙6例,低钾、低钠1例,低氯1例,正常3例。结论：在临床中应尽量选用对Q-T间期影响较少的抗精神病药物,常规复查心电图、血生化,有Q-T间期延长者可以补充电解质来纠正。     

继发性Q-T间期延长预后分析

目的分析继发性Q-T间期延长的预后。方法回顾性分析126例Q-T间期延长的临床资料。结果126例中,预后不良者42例,占33.3%,其中频发室性早搏3例,突然发生室性心动过速(室速)或心室纤颤(室颤)18例,猝死20例。继发性Q-T间期延长,出现T波形态改变的,提示有发生严重室性心律失常或猝死的危险。药物引起的QT间期延长者46例,导致严重的室性心律失常或室颤。4例在原发病引起Q-T间期延长情况下并发低钾,均发生严重心律失常;低钾合并低镁13例,均并发严重室性心律失常或猝死。结论Q-T间期延长患者易发生心律失常,引起严重的并发症,临床上应引起足够的重视。     

全面QT/QTc研究、药物浓度QTc研究与心脏安全

非抗心律失常药物特别是抗肿瘤药物会影响心脏复极化,进而延长QT间期,导致患者出现恶性心律失常,发生心源性猝死.近年来,此类药物不良反应越来越受到监管部门、药物研发企业以及临床医生的关注.随着《E14:非抗心律失常药物QT/QTc间期延长及致心律失常潜力的临床评价》和《S7B:人用药品延迟心室复极化(QT间期延长)潜在作...     

心电图的Q-T间期和Q-T间期离散度

心电图上的Q-T间期是指ORS波群起点至T波终点这段时间,反映心室除极开始到心室复极结束的时间间隔,代表心室除极和复极的时间总和。Q-T间期等于心室有效不应期和相对不应期的总和,代表心室的总不应期,Q-T间期变化与心室复极过程的改变有关,并且受很多因素如心率、性别、电解质、药物特别是抗心律失常药物和某些疾病的影响,也可以说凡能改变动作电位2相和3相时程的因素均能引起Q-T间期改变。在影响Q-T间期的众多因素中,以心率对其影响最大,当心率增快时QT间期缩短,而心率减慢时则Q-T间期延长。为了得到可靠的Q-T间期值,临床心电图学提出心率     

对特发性Q-T间期延长综合征的临床探讨

特发性Q-T间期延长综合征是复极延长为尖端扭转型心动过速是一种室性快速心律失常,可引起昏厥或死亡。心电图出现Q-T间隙延长,室性心律失常。其由电解质平衡紊乱,服用影响心室复极的药物等。还可能伴有先天性耳聋,其中最常见的是JerveII-Lange-NeiL-son综合征（常染色体隐性遗传性耳聋）、Romano-Wavcl综合征（常染色体显性遗传性耳聋）。患者有明显Q-T间期延长和形态异常,有发生尖端扭转型室性心动过速的危险并可致死亡。发病时常用β受体阻滞剂首选恢复左右星状神经结的平衡,对心跳暂停依赖性治疗以提高心率为主。除纠正病因外,对症治疗用异丙肾、阿托品或起搏治疗。而禁用Ia、Ic或Ⅲ类心律失常药物。     

抗心律失常药的药物相互作用

本文主要讨论最常见的抗心律失常药地高辛 和胺碘酮与其它药物间可能发生的药物相 互作用。 为改善治疗效果,临床上常将几种抗心律失常药物联合应用。但作用相似的药物合用时,因可能引起加和作用而应避免。 按新的抗心律失常分类法,各类药物中仍有部分共性,如Iａ和Ｉｃ中的药物及索他洛尔或胺碘酮可延长ＱＴ间期,易致尖端扭曲性心律失常（ＴＤＰ）;因此,合用Ia和Ｉｃ或它们与索他洛尔、胺碘酮合用可增加ＱＴ间期延长的危险,致室颤和猝死,因此,不宜合用。 许多抗心律失常药物有负性肌力作用,如Iａ类、Ｂ阻滞剂和维拉帕米,这些…     

抗心律失常药物对蟾酥致小鼠心律失常的影响

比较苯妥英钠、利多卡因(钠通道阻滞药)、普萘洛尔(β肾上腺素受体拮抗药)、胺碘酮(延长动作电位时程药)和维拉帕米(钙通道阻滞药)对蟾酥诱导小鼠心律失常的抑制作用及对离体小鼠心脏的蟾酥致死量的影响。采用动态心电图记录蟾酥诱导小鼠心律失常。观察模型组和各给药组心电图的P-R间期、QRS时程、Q-T间期、T波幅度和HR的变化,统计各心律失常发生率、存活率及心律失常评分。采用离体小鼠心脏灌流,记录心脏的蟾酥致死量。与模型组相比,苯妥英钠组的QRS时程缩短且心率减慢;室性心律失常的发生率降低,存活率增高;显著增加离体小鼠心脏的蟾酥累积致死量。利多卡因组与模型组相比,P-R间期和QRS时程缩短;室性心律失常发生率降低;显著增加离体小鼠心脏的蟾酥累积致死量。普萘洛尔组与模型组相比,P-R间期、QRS时程和Q-T间期缩短;室上性及室性心律失常的发生率降低。胺碘酮显著减慢模型小鼠的心率并且降低模型小鼠室性心律失常的发生率。维拉帕米显著延长模型小鼠P-R间期,抑制Q-T间期延长;减少室上性及室性心律失常的发生;显著减少离体小鼠心脏的蟾酥累积致死量。整体动物实验中,苯妥英钠对蟾酥诱导小鼠的心律失常最有效,其次是利多卡因和普萘洛尔,...     

ICH E14《非抗心律失常药所致QT延长临床评价:问答第3次修订版》介绍

为了发现并判断非抗心律失常药所致的QT间期延长,人用药品技术要求协调国际会议（ICH）发布了E14《非抗心律失常药致QT/QTc间期延长及潜在致心律失常作用的临床评价指导原则》。2008年ICH发布了该指导原则的问答（E14 Q&As）,对一些具体问题做了说明,随后又对问答做了第3次修订,问答数较原版增加了1倍。美国食品药品管理局（FDA）于2017年6月对第3次修订版予以转发。介绍该修订版的详细内容,希望对我国非抗心律失常药临床评价相关方面的研究和监管工作有益。     

抗感染药物引起的心律失常及其机制的研究进展

药物诱发性心律失常,以抗心律失常药引起最为常见,但随着抗感染药物的广泛应用,有关其不良反应的报道日渐增多,近年来报道的引起心律失常如Q-T间期延长和尖端扭转型室性心动过速(TdP)令人瞩目,虽然相对少见,然而一旦发生,后果多较严重。当发生TdP时,患者可出现心悸、晕厥、抽搐,     

药物相关性长QT间期综合征的研究进展

本文从长QT间期综合征的临床特征、机制与影响因素、药物相关性长QT间期综合征及临床对其防治的国内外研究进展作一综述,提出临床药师需要关注易致QT间期延长的药品使用,预防临床发生药物致急性心律失常事件,以促进临床合理用药、降低药物不良反应。     

A novel approach to data processing of the QT interval response in the conscious telemetered beagle dog

INTRODUCTION: Drug-induced QT interval prolongation may lead to ventricular arrhythmias. The aim of the study was to optimize QT interval data processing to quantify drug-induced QT interval prolongation in the telemetry instrumented conscious dog model. METHODS: The test substances cisapride, dofetilide, haloperidol, and terfenadine and corresponding vehicles were given to male and female beagle dogs during two consecutive 90-min intravenous infusions. Cardiovascular parameters were recorded for 24 h and exposure to the drugs was measured. The delayed response in the QT interval after an abrupt change in heart rate was investigated. Eight mathematical models to describe the QT interval-heart rate relationship were compared and different sets of covariates were used to quantify the drug-induced effect on the QT interval. RESULTS: After an abrupt decrease in heart rate, a 75% adaptation of the QT interval was reached after 54+/-9 s. A linear model was preferred to correct the drug-induced effect on the QT interval for heart rate, vehicle effect, serial correlation, plasma concentration and time of day. All test substances significantly prolonged the QT interval. DISCUSSION: To optimize the processing of QT interval data, the delay in QT interval response after an abrupt change in heart rate should be considered. The QT interval-heart rate relationship and vehicle response were individual-specific and corrections were therefore made individually. When estimating the drug-induced effect on the QT interval it is considered advantageous to use plasma concentration as a covariate, as well as adjusting for vehicle effect and serial correlation in measurements. The conscious dog model detected significant increases in the QT interval for all test substances investigated.     

药物心脏安全性评估与全面QT/QTc研究

许多非抗心律失常药物可以导致心电图QT间期延长,甚至引发尖端扭转型室性心动过速.因此在新药上市前,进行的心脏安全性评估,应该包括药物对QT间期影响的特点.全面QT/QTC研究旨在通过测量QT间期,明确药物是否具有延长QT间期的作用,判断其引发恶性心律失常的风险,并为决定药物是否进入下一步研发提供数据支持.     

抗新型冠状病毒药物致QT间期延长的文献复习及药学监护

本文对新型冠状病毒肺炎患者临床用药方案涉及的抗病毒药物致QT间期延长的文献报道情况进行复习。根据目前文献复习结果可知,洛匹那韦/利托那韦和磷酸氯喹存在引起QT间期延长进而引发尖端扭转型室速的潜在风险。在新型冠状病毒肺炎患者中使用此类药物需关注由此带来的用药风险,熟悉临床上常用的可引起QT间期延长的药物,提高识别患者QT间期延长的易感因素和药物相互作用的能力,重视心电图、电解质管理来预防临床潜在的药物致急性心律失常事件,以降低新型冠状病毒肺炎患者的药物不良反应,避免药源性损害。     

Safety of droperidol in behavioural emergencies

By the year 2000, droperidol had become a standard drug for the treatment of behavioural emergencies in both psychiatric and medical settings. In 2001, the US FDA issued a ‘black box’ warning, citing cases of QT prolongation and/or torsades de pointes. As a result, the use of droperidol has been sharply circumscribed. The authors will review the literature on antipsychotic medications in general, focusing on droperidol in particular, with regard to QT interval prolongation, dysrhythmia, and sudden death. In addition, the mechanism of drug-induced QT interval prolongation will be discussed. The authors will then review their extensive experience with droperidol. The authors conclude that, while in theory droperidol may prolong the QT interval to an extent similar to thioridazine, its long history of clinical use has shown no pattern of sudden deaths analogous to those that provoked the FDA warning. Although the numbers presented by the FDA initially appear alarming, after further evaluation it is clear that more definitive studies should have been carried out. Droperidol is safe, extremely effective, and now underused as a treatment for severely agitated or violent patients.     

Clinical relevance and management of drug-related QT interval prolongation

Much attention recently has focused on drugs that prolong the QT interval, potentially leading to fatal cardiac dysrhythmias (e.g., torsade de pointes). We provide a detailed review of the published evidence that supports or does not support an association between drugs and their risk of QT prolongation. The mechanism of drug-induced QT prolongation is reviewed briefly, followed by an extensive evaluation of drugs associated with QT prolongation, torsade de pointes, or both. Drugs associated with QT prolongation are identified as having definite, probable, or proposed associations. The role of the clinician in the prevention and management of QT prolongation, drug-drug interactions that may occur with agents known to affect the QT interval, and the impact of this adverse effect on the regulatory process are addressed.     

Safety of droperidol in behavioural emergencies

By the year 2000, droperidol had become a standard drug for the treatment of behavioural emergencies in both psychiatric and medical settings. In 2001, the US FDA issued a 'black box' warning, citing cases of QT prolongation and/or torsades de pointes. As a result, the use of droperidol has been sharply circumscribed. The authors will review the literature on antipsychotic medications in general, focusing on droperidol in particular, with regard to QT interval prolongation, dysrhythmia, and sudden death. In addition, the mechanism of drug-induced QT interval prolongation will be discussed. The authors will then review their extensive experience with droperidol. The authors conclude that, while in theory droperidol may prolong the QT interval to an extent similar to thioridazine, its long history of clinical use has shown no pattern of sudden deaths analogous to those that provoked the FDA warning. Although the numbers presented by the FDA initially appear alarming, after further evaluation it is clear that more definitive studies should have been carried out. Droperidol is safe, extremely effective, and now underused as a treatment for severely agitated or violent patients.     

Prediction of drug-induced QT interval prolongation in telemetered common marmosets

Drug-induced QT interval prolongation is a critical issue in development of new chemical entities, so the pharmaceutical industry needs to evaluate risk as early as possible. Common marmosets have been in the limelight in early-stage development due to their small size, which requires only a small amount of test drug. The purpose of this study was to determine the utility of telemetered common marmosets for predicting drug-induced QT interval prolongation. Telemetry transmitters were implanted in common marmosets (male and female), and QT and RR intervals were measured. The QT interval was corrected for the RR interval by applying Bazett's and Fridericia's correction formulas and individual rate correction. Individual correction showed the least slope for the linear regression of corrected QT (QTc) intervals against RR intervals, indicating that it dissociated changes in heart rate most effectively. With the individual correction method, the QT-prolonging drugs (astemizole, dl-sotalol) showed QTc interval prolongations and the non-QT-prolonging drugs (dl-propranolol, nifedipine) did not show QTc interval prolongations. The plasma concentrations of astemizole and dl-sotalol associated with QTc interval prolongations in common marmosets were similar to those in humans, suggesting that the sensitivity of common marmosets would be appropriate for evaluating risk of drug-induced QT interval prolongation. In conclusion, telemetry studies in common marmosets are useful for predicting clinical QT prolonging potential of drugs in early stage development and require only a small amount of test drug.     

QT-RR relationships and suitable QT correction formulas for halothane-anesthetized dogs

Several QT correction (QTc) formulas have been used for assessing the QT liability of drugs. However, they are known to under- and over-correct the QT interval and tend to be specific to species and experimental conditions. The purpose of this study was to determine a suitable formula for halothane-anesthetized dogs highly sensitive to drug-induced QT interval prolongation. Twenty dogs were anesthetized with 1.5% halothane and the relationship between the QT and RR intervals were obtained by changing the heart rate under atrial pacing conditions. The QT interval was corrected for the RR interval by applying 4 published formulas (Bazett, Fridericia, Van de Water, and Matsunaga); Fridericia's formula (QTcF = QT/RR(0.33)) showed the least slope and lowest R(2) value for the linear regression of QTc intervals against RR intervals, indicating that it dissociated changes in heart rate most effectively. An optimized formula (QTcX = QT/RR(0.3879)) is defined by analysis of covariance and represents a correction algorithm superior to Fridericia's formula. For both Fridericia's and the optimized formula, QT-prolonging drugs (d,l-sotalol, astemizole) showed QTc interval prolongation. A non-QT-prolonging drug (d,l-propranolol) failed to prolong the QTc interval. In addition, drug-induced changes in QTcF and QTcX intervals were highly correlated with those of the QT interval paced at a cycle length of 500 msec. These findings suggest that Fridericia's and the optimized formula, although the optimized is a little bit better, are suitable for correcting the QT interval in halothane-anesthetized dogs and help to evaluate the potential QT prolongation of drugs with high accuracy.     

全面QT研究的临床试验设计

药物导致的心电图QT/QTc间期延长,虽然发生率不高,但潜在危险性大,严重的可诱发室性心律失常甚至猝死。2005年5月,人用药品注册技术要求国际协调会正式颁布了《非抗心律失常药物潜在导致QT/QTc间期延长和心律失常的临床评价指南》(E14)。本文根据该指南及从大量已完成的研究中总结的经验讨论全面QT研究的临床试验设计要点,以期对今后中国的相关研究提供有益的指导。