CLINICAL PHARMACOLOGY OF LOOP DIURETICS

袢利尿剂的临床药理学

• 批准号: 6200550
• 负责人: D CRAIG BRATER
• 金额: $ 28.27万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6200550
• 关键词: acetazolamide; cardiovascular disorder chemotherapy; chlorothiazide; clinical research; congestive heart failure; diuretics; drug interactions; furosemide; human subject; human therapy evaluation; longitudinal human study; pharmacokinetics; renal tubular transport; sodium; spironolactone; sulfonamides

DESCRIPTION: (adapted from Investigator's abstract) During the past grant period, the investigators performed a variety of studies asking clinically pertinent questions about more effective uses of diuretics. In the current proposal, they propose two large new studies that logically extend their previous work. The aim of the first study is to delineate the mechanism of the pharmacodynamic resistance to loop diuretics that occurs in patients with congestive heart failure (CHF). This resistance could occur by increased proximal tubular reabsorption of sodium, increased distal reabsorption of sodium and/or a change in the dynamics of the interaction of the loop diuretic with the Na-K-2Chl transporter of the loop of Henle. The answers to these questions should illuminate the mechanisms of sodium retention in CHF and thus allow more rational and effective use of diuretic combinations. This study will entail using diuretics with sites of action at different portions of the nephron as probes of this pathophysiology. They will employ methods familiar to them in clinical studies designed to systematically examine the role of different nephron sites in causing diuretic resistance. They will also perform a clinic-based study in which they will attempt to define causes for clinical deterioration in patients with CHF. This study will utilize a unique electronic medical record at the University of Indiana, the Regenstreif Medical Record System (RMRS). This system captures a wealth of clinical data that will be extracted and linked with compliance data, plasma renin and aldosterone activity and quality of life assessments obtained during this study to answer a series of focused questions. Each patient studied will be followed for at least one year. The investigators will perform multivariate analyses to determine causes of clinical deterioration. These data will provide insights into the causes and pathophysiology of decompensation in patients with CHF, thus enhancing our understanding of this increasingly prevalent disease and leading to better therapeutic strategies.

描述：（根据调查员的摘要改编）在过去的赠款期间 时期，研究人员进行了各种研究，要求临床 关于利尿剂的更有效用途的相关问题。在电流中 提案，他们提出了两项​​大型新研究，从逻辑上扩展了他们的 以前的工作。第一项研究的目的是描述 在患者患者中，对环循环利尿剂的药效动力学性 充血性心力衰竭（CHF）。这种阻力可能会增加 钠的近端管状重吸收，远端重吸收的远端重吸收 钠和/或环路相互作用的动力学变化 带有Henle循环的NA-K-2CHL转运蛋白。这些答案 问题应阐明CHF中钠保留的机制，从而 允许更多理性和有效地利用利尿剂组合。这项研究会 在使用利尿剂与在不同部分的不同部分使用利尿剂 肾单位作为这种病理生理学的探针。他们将采用熟悉的方法 它们在旨在系统地检查的临床研究中 引起利尿剂抗性的不同肾单位位点。 他们还将进行基于诊所的研究，他们将尝试 定义CHF患者临床恶化的原因。这项研究会 在印第安纳大学利用独特的电子病历， Regenstreif病历系统（RMR）。该系统捕获了很多 将提取并与合规性数据链接的临床数据，等离子体 肾素和醛固酮的活动以及在期间获得的生活质量评估 这项研究回答了一系列集中问题。每个研究的患者将 遵循至少一年。调查人员将执行多变量 分析以确定临床恶化的原因。这些数据将提供 对患者的代偿性原因和病理生理的见解 CHF，从而增强了我们对这种日益普遍疾病的理解 并导致更好的治疗策略。