吡咯他尼及其他三种“袢”利尿剂的肾脏作用

Renal actions of piretanide and three other "loop" diuretics.

作者信息

McNabb W R, Noormohamed F H, Brooks B A, Lant A F

出版信息

Clin Pharmacol Ther. 1984 Mar;35(3):328-37. doi: 10.1038/clpt.1984.38.

DOI:10.1038/clpt.1984.38

Abstract

Thirty-nine clearance studies were performed in 17 healthy subjects under conditions of maximal hydration or hydropenia to compare the effects on renal solute and water handling of three sulfamoylbenzoic acid derivatives-piretanide, bumetanide, and furosemide-and the phenoxyacetic acid diuretic ethacrynic acid. Except for furosemide, which caused a 7% fall in effective renal plasma flow (ERPF), and ethacrynic acid, which reduced both the glomerular filtration rate (16%) and ERPF (23%) during maximal hydration, changes in hemodynamics were insignificant. At peak saluresis piretanide induced a mean reduction of -18.3% +/- 4.9% in fractional free-water clearance during hydration and -73.2% +/- 5.9% in fractional free-water reabsorption during hydropenia. The other sulfamoylbenzoates lowered fractional clearance and reabsorption of free water to similar extents, implying a major site of action within the medullary portion of the ascending limb. Ethacrynic acid reduced fractional free-water clearance to a greater degree than did the sulfamoylbenzoates. The mean reduction in fractional free-water reabsorption after ethacrynic acid (71.4% +/- 8.2%) was of the same order as that caused by the sulfamoylbenzoates. Similar excretory maxima for sodium, chloride, potassium, calcium, and magnesium were achieved for all four diuretics. Except for piretanide under hydropenia, sulfamoylbenzoate action did not change urinary pH. Ethacrynic acid consistently lowered urinary pH. During hydration piretanide induced phosphaturia (35.3% +/- 8.8%) and uricosuria (40.9% +/- 9.1%). Both bumetanide and piretanide increased fractional urate clearance during hydropenia (16.7% +/- 5.6% and 34.2% +/- 10.5%). There were no changes in phosphate or urate excretion after ethacrynic acid. Our data support the view that sulfamoylbenzoate diuretics exert additional effects on proximal tubular segments that are not shared by ethacrynic acid. Renal responses to piretanide most closely resemble those to bumetanide.

摘要

在17名健康受试者处于最大水合状态或缺水状态下进行了39项清除率研究，以比较三种氨磺酰苯甲酸衍生物（吡咯他尼、布美他尼和呋塞米）以及苯氧乙酸类利尿剂依他尼酸对肾脏溶质和水代谢的影响。除了呋塞米使有效肾血浆流量（ERPF）下降7%，以及依他尼酸在最大水合状态下使肾小球滤过率降低16%、ERPF降低23%外，血流动力学变化不显著。在利尿峰值时，吡咯他尼在水合状态下使自由水清除分数平均降低-18.3%±4.9%，在缺水状态下使自由水重吸收分数降低-73.2%±5.9%。其他氨磺酰苯甲酸类药物使自由水清除分数和重吸收分数降低到相似程度，这意味着其主要作用部位在髓袢升支髓质部。依他尼酸比氨磺酰苯甲酸类药物更能降低自由水清除分数。依他尼酸后自由水重吸收分数的平均降低（71.4%±8.2%）与氨磺酰苯甲酸类药物所致的降低程度相当。所有四种利尿剂对钠、氯、钾、钙和镁的排泄最大值相似。除了缺水状态下的吡咯他尼外，氨磺酰苯甲酸类药物的作用不改变尿液pH值。依他尼酸持续降低尿液pH值。在水合状态下，吡咯他尼引起磷酸盐尿（35.3%±8.8%）和尿酸尿（40.9%±9.1%）。在缺水状态下，布美他尼和吡咯他尼均增加尿酸清除分数（分别为16.7%±5.6%和34.2%±10.5%）。依他尼酸后磷酸盐或尿酸排泄无变化。我们的数据支持以下观点，即氨磺酰苯甲酸类利尿剂对近端肾小管节段有依他尼酸所没有的额外作用。肾脏对吡咯他尼的反应与对布美他尼的反应最为相似。