Schotborgh C E, Wilde A A
Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Netherlands.
Cardiovasc Res. 1997 Apr;34(1):73-80. doi: 10.1016/s0008-6363(97)00036-9.
Sulfonylurea derivatives are hypoglycemic drugs frequently used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). In the beta-cell sulfonylureas act by blocking ATP-sensitive potassium channels (K.ATP channels). In several organ systems, including the cardiovascular system, sulfonylurea receptors and functional K.ATP channels have been identified. In the heart their role is not clear: an endogenous cardioprotective effect has been suggested. There is no doubt that K.ATP channels are effectively blocked by sulfonylureas. In the last decade sulfonylureas have been widely used as a pharmacological tool in experimental (cardiac) research. Blockade of K.ATP channels is the proposed cellular mechanism of action for all sulfonylurea-related effects. However, other membrane currents are affected as well. In addition, myocardial metabolism is modified by sulfonylurea pretreatment. Hence, it should seriously be questioned whether these drugs are suitable in assessing involvement of cardiac K.ATP channels in, for example, ischemia-related events. The detrimental effects of sulfonylureas in experimental studies on myocardial ischemia have led to speculation whether the widespread use of these drugs in patients with NIDDM, most often suffering from accompanying ischemic heart disease, should be reconsidered. However, a review of the clinical literature reveals that the most consistent finding is a lower incidence of ventricular arrhythmias associated with the use of glibenclamide, while no excess mortality has been shown for this agent in NIDDM with ischemic heart disease. Despite some direct effects on systemic and coronary vasculature, there are, at present, no firm clinical data on the basis of which sulfonylurea derivatives should be withheld from the cardiac patient.
磺脲类衍生物是常用于治疗非胰岛素依赖型糖尿病（NIDDM）的降糖药物。在β细胞中，磺脲类药物通过阻断ATP敏感性钾通道（K.ATP通道）发挥作用。在包括心血管系统在内的多个器官系统中，已鉴定出磺脲类受体和功能性K.ATP通道。在心脏中它们的作用尚不清楚：有人提出存在内源性心脏保护作用。毫无疑问，磺脲类药物可有效阻断K.ATP通道。在过去十年中，磺脲类药物已被广泛用作实验性（心脏）研究中的药理学工具。阻断K.ATP通道是所有磺脲类相关效应的拟议细胞作用机制。然而，其他膜电流也会受到影响。此外，磺脲类药物预处理会改变心肌代谢。因此，这些药物是否适合用于评估心脏K.ATP通道在例如缺血相关事件中的参与情况，应受到严重质疑。磺脲类药物在心肌缺血实验研究中的有害作用引发了人们的猜测，即对于NIDDM患者（大多数常伴有缺血性心脏病）广泛使用这些药物是否应重新考虑。然而，对临床文献的回顾显示，最一致的发现是使用格列本脲与室性心律失常发生率较低相关，而在伴有缺血性心脏病的NIDDM患者中，未显示该药物有额外死亡率。尽管对全身和冠状动脉血管有一些直接影响，但目前尚无确凿的临床数据表明应不给心脏病患者使用磺脲类衍生物。
