Arrhythmogenic actions of antiarrhythmic drugs.
Arrhythmogenic actions of antiarrhythmic drugs.
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抗心律失常药物的致心律失常作用。
DOI：
10.1016/0002-9149(87)90196-2
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Wit,AL
中科院分区：
文献类型：
--
作者：
Rosen,MR;Wit,AL
心律失常可由脉冲传播异常或脉冲起始异常引起。当抗心律失常药物引发心律失常时，最常见的机制似乎是（1）传导阻滞或折返，以及（2）异常冲动起始，可能由后去极化触发。药物对传导的影响可能是由于它们对快钠通道、慢钙通道的作用或它们延长复极的能力。抑制快速钠或缓慢钙进入的药物发挥毒性作用的程度在很大程度上取决于其与通道受体位点的结合特性。这种毒性代表了这些药物治疗效果的连续性。控制药物进入结合位点的因素，包括脂溶性，分子大小和电离程度，进行审查，因为是药物引起的复极变化的传导异常的贡献。药物诱导冲动启动异常的机制仍然是一个猜测的问题。显然，增加内向平台电流或减少复极钾离子电流的药物会增加风险。此外，有证据表明继发于延长复极的早期后除极可能是心律失常（包括尖端扭转型室性心动过速）的原因。抗心律失常药物可能有助于这种类型的快速性心律失常的机制进行了审查。
Cardiac arrhythmias may result from abnormalities of impulse propagation or abnormalities of impulse initiation. When arrhythmias are initiated by antiarrhythmic drugs, the most common mechanisms appear to be (1) conduction block or reentry, and (2) abnormal impulse initiation, which may be triggered by afterdepolarizations. The effects of drugs on conduction may result from their actions on the fast sodium channel, the slow calcium channel or their ability to prolong repolarization. The extent to which a drug that depresses fast sodium or slow calcium entry will exert its toxic effects depends in large part on its binding characteristics to its channel receptor site. Such toxicity represents a continuum for the therapeutic effects of these drugs. The factors that control drug access to binding sites, including lipid solubility, molecular size and extent of ionization, are reviewed, as are the contributions to conduction abnormalities of drug-induced changes in repolarization. The mechanisms whereby drugs induce abnormalities of impulse initiation are still a matter of conjecture. Apparently, drugs that increase inward plateau currents or decrease repolarizing potassium ion currents carry increased risk. Moreover, there is evidence for the role of early after depolarizations occurring secondary to prolonged repolarization as a possible cause of arrhythmias, including torsades de pointes. The mechanisms whereby antiarrhythmic drugs may contribute to this type of tachyarrhythmia are reviewed.