Brater D C
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5124, USA.
Am J Med Sci. 2000 Jan;319(1):38-50. doi: 10.1097/00000441-200001000-00004.
The diuretics in our therapeutic armamentarium have predictable effects based on their nephron sites of action. All but spironolactone must reach the lumen or urinary side of the nephron to exert their effects. Thus, in settings of decreased renal function, doses must be increased to deliver more diuretic into the urine. In other edematous disorders, such as congestive heart failure (CHF) and cirrhosis, adequate amounts of diuretic reach the site of action if renal function is satisfactory. Diminished response in these conditions is caused by a decrease in the sensitivity of the nephron to the diuretic, the mechanism of which is unknown. Rather than using large single doses of diuretic in CHF and cirrhosis, multiple doses and/or combinations of diuretics should be used. Therefore, thiazide diuretics coupled with loop diuretics are most logical because they affect different nephron sites and the thiazide counteracts distal nephron hypertrophy that may occur with loop diuretics alone. Ample studies have shown that such combinations can result in a truly synergistic response. Using pharmacokinetics and pharmacodynamics of diuretics, we can design therapeutic regimens in which satisfactory control of fluid and electrolyte homeostasis can be achieved in the vast majority of patients.
我们治疗药物中的利尿剂根据其在肾单位的作用部位会产生可预测的效果。除螺内酯外，所有利尿剂都必须到达肾单位的管腔或尿液侧才能发挥作用。因此，在肾功能下降的情况下，必须增加剂量以便将更多利尿剂输送到尿液中。在其他水肿性疾病中，如充血性心力衰竭（CHF）和肝硬化，如果肾功能良好，足量的利尿剂会到达作用部位。这些情况下反应减弱是由于肾单位对利尿剂的敏感性降低，其机制尚不清楚。在CHF和肝硬化中，不应使用大剂量单一利尿剂，而应使用多次剂量和/或联合使用利尿剂。因此，噻嗪类利尿剂与襻利尿剂联用最为合理，因为它们作用于不同的肾单位部位，且噻嗪类药物可对抗单独使用襻利尿剂时可能出现的远端肾单位肥大。大量研究表明，这种联合使用可产生真正的协同反应。利用利尿剂的药代动力学和药效学，我们可以设计出治疗方案，从而在绝大多数患者中实现对液体和电解质稳态的满意控制。
