Huupponen R
Med Toxicol. 1987 May-Jun;2(3):190-209. doi: 10.1007/BF03259864.
Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.
磺脲类药物广泛应用于糖尿病的治疗。自大学组糖尿病项目(UGDP)结果公布以来,关于其可能的心血管副作用的讨论一直很热烈,有时甚至很激烈。UGDP关于甲苯磺丁脲对心血管系统不良影响的初步研究结果受到了批评,特别是在研究设计方面存在缺陷。迄今为止发表的其他关于磺脲类药物对心血管发病率和死亡率影响的流行病学研究结果相互矛盾。这是可以理解的,因为涉及的因素非常复杂。这些研究大多只使用了甲苯磺丁脲,其结果不一定能直接外推到其他磺脲类药物。只有进行得当的前瞻性研究才能提供关于这个问题的更多信息。在体外动物模型中,几种磺脲类药物的高浓度可能对心肌有正性肌力作用,但体内人体研究并不支持磺脲类药物具有临床上显著正性肌力作用的观点。高浓度的甲苯磺丁脲或格列本脲(优降糖)可能影响离体器官的心肌代谢,但这些发现的潜在临床意义仍不清楚。一些流行病学和实验研究将口服降糖治疗与心律失常的发生或洋地黄毒性增加联系起来。只有少数结果可供参考,在这方面不同磺脲类药物之间可能存在差异。一些磺脲类药物被认为具有抗聚集特性。特别是格列齐特已被研究,但该类别的其他一些化合物在短期研究中也有效果。如果得到证实,这些对止血的作用将值得关注。在过去几年里,磺脲类药物对血脂,尤其是对高密度脂蛋白胆固醇的影响得到了广泛讨论。有人认为高密度脂蛋白胆固醇浓度降低与磺脲类药物治疗有关。然而,最近使用不同磺脲类药物进行的横断面和纵向研究并未证实这些发现。氯磺丙脲,在较小程度上还有甲苯磺丁脲,可能导致稀释性低钠血症并加重现有的心力衰竭。格列本脲可能增加肾脏对水的清除率。