每日一题_2022.06.22

A 76-year-old man develops right ventricular failure on postoperative day three after implantation of a left ventricular assist device. Furosemide, 120 mg IV every 6 hours, is administered and, initially, the patient’s response is vigorous, but after four days, his response is significantly diminished.

Which of the following most likey explains the patient’s decreased response to the furosemide?

A. Atrophy of cells in the distal convoluted tubule

B. Increased protein binding of furosemide

C. Competitive inhibition of furosimide transport

D. Decreased stimulation of the renin-angiotensin-aldosterone system

答案解析：

袢利尿剂抵抗是充血性心力衰竭长期治疗的常见并发症。呋塞米可有效减弱髓袢升支粗段对钠和水的重吸收，但这可使远曲小管(DCT)的管腔钠浓度更高。DCT中的细胞对这种钠浓度增加的反应发生肥大，并吸收更多的钠和水，从而降低了呋塞米的有效性。

髓袢利尿剂作用于髓袢升支粗段管腔侧的靶点。为了达到其靶点，呋塞米必须在肾小球滤过，然后通过有机离子转运蛋白分泌到肾小管腔内。血尿素氮和其他有机酸竞争该转运蛋白上的结合位点，使呋塞米分泌效率降低。

有效利尿引起的血浆容量减少导致肾-血管紧张素-醛固酮系统和交感神经系统激活。这降低了肾小球滤过率，导致肾小管流量减少，钠和水的重吸收增加。

呋塞米与血浆蛋白结合可增加药物的有效性，因为分泌至肾小管腔内需要血浆结合。低白蛋白血症常见于心力衰竭，可增强呋塞米转化为其非活性形式。血浆蛋白结合率增加而不是降低呋塞米作为袢利尿剂的有效性，这就是呋塞米与白蛋白联合给药已被证实可改善肝硬化和肾病综合征患者对利尿剂反应的原因。

正确答案：C