Clinical features and basic mechanisms of quinidine-induced arrhythmias.
Clinical features and basic mechanisms of quinidine-induced arrhythmias.
复制标题
奎尼丁诱发心律失常的临床特征和基本机制。
DOI：
10.1016/s0735-1097(86)80032-8
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发表时间：
1986
影响因子：
24
通讯作者：
Woosley,RL
中科院分区：
文献类型：
--
作者：
Roden,DM;Thompson,KA;Hoffman,BF;Woosley,RL
奎尼丁治疗是获得性长QT综合征和形态学上独特的快速性心律失常尖端扭转型室性心动过速的最常见原因之一。我们机构和其他机构的临床数据显示了一些特征性特征：奎尼丁血浆浓度通常较低，不存在明显的QRS延长，低钾血症频繁发生，在发作开始前心率突然减慢几乎不变。血浆奎尼丁浓度和这种不良药物作用之间缺乏相关性，这可能是外部因素（例如，低钾血症）调节奎尼丁在体内的反应或一个或多个未测量的活性代谢物发挥作用。因此，在犬浦肯野纤维中检查了细胞外钾和刺激率的改变对奎尼丁电生理效应的影响。有人发现，触发自律性的一种形式，早期后去极化，可靠地产生奎尼丁的存在时，细胞外钾降低，刺激速率减慢。最近，许多奎尼丁代谢物以及常见杂质二氢奎尼丁的作用在犬浦肯野纤维中以类似的方式进行了表征。虽然奎尼丁是最有效的物质测试，二氢奎尼丁和3-羟基奎尼丁延长动作电位，并产生早期后去极化奎尼丁在长周期length. Quinidine诱导的尖端扭转型室性心动过速是一种潜在的致命的药物不良反应，发生在1至3%的患者。低钾血症和心率减慢通常在临床环境中观察到，在组织浴中，当细胞外钾降低和刺激速率减慢时，奎尼丁及其几种代谢产物诱导异常自动行为。它的结论是早期后除极，触发自律性的一种形式，可能是负责诱导奎尼丁诱导的心律失常在人类。
Quinidine therapy is one of the most common causes of the acquired long QT syndrome and the morphologically distinctive tachyarrhythmia torsade de pointes. Clinical data from our institution and others have revealed a number of characteristic features: quinidine plasma concentrations are generally low, marked QRS prolongation is absent, hypokalemia is frequent and abrupt heart rate slowing just before the initiation of a paroxysm is almost invariable. The lack of correlation between plasma quinidine concentrations and this adverse drug effect raises the possibility either that external factors (for example, hypokalemia) modulate the response to quinidine in vivo or that one or more unmeasured active metabolites play a role.Therefore, the effects of alterations in extracellular potassium and stimulation rate on the electrophysiologic effects of quinidine were examined in canine Purkinje fibers. It was found that a form of triggered automaticity, early afterdepolarizations, is reliably produced in the presence of quinidine when extracellular potassium is lowered and the stimulation rate is slowed. More recently, the effects of a number of quinidine metabolites, as well as the commonly found impurity dihydroquinidine, were characterized in canine Purkinje fibers in a similar fashion. Although quinidine was the most potent of the substances tested, both dihydroquinidine and 3-hydroxyquinidine prolonged action potential and produced early afterdepolarizations as did quinidine at long cycle lengths.Quinidine-induced torsade de pointes is a potentially lethal adverse drug effect, occurring in 1 to 3% of patients. Hypokalemia and slow heart rates are commonly observed in a clinical setting and, in the tissue bath, quinidine and several of its metabolites induce abnormal automatic behavior when extracellular potassium is lowered and stimulation rate is slowed. It is concluded that early afterdepolarizations, a form of triggered automaticity, may be responsible for induction of quinidineinduced arrhythmias in humans.