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1、第23章 利尿药和脱水药 Diuretics and Dehydrate agents,华中科技大学同济医学院药理学系,授课教师 金满文,2009年10月,本次课要求掌握的主要内容,1.利尿药的分类及代表药 2.各类利尿药的作用部位和作用机制 3.噻嗪类利尿药的临床应用和不良反应 4.呋塞米的临床应用和不良反应 5.螺内酯的临床应用和不良反应 6.甘露醇的临床应用,中文：利尿药是直接作用于肾脏，增加电解质和水的排出，使尿量增多的药物。,2,定义(本版教科书)：,第一节 利尿药,英文：Diuretics are drugs that increase the rate of urine flow
2、 and sodium excretion.,很准确！,欠准确！,？,但是，并非增加尿量的药物都是利尿药，如强心苷改善心衰，增加心排量，也使尿量增加，但其不作为利尿药。,Some drugs can increase urine flow by nonrenal mechanisms (e.g. by increasing cardiac output in a patient with congestive heart failure), but these drugs are not generally regarded as diuretics.,3,利尿药 增加尿量和排钠，在用高血压、
3、心衰、肾衰、肾病综合征和肝硬化等病变时，来调节体液的量和/或成份。,Diuretics increase the rate of urine flow and sodium excretion and are used to adjust the volume and/or composition of body fluids in a variety of clinical situations, including hypertension, heart failure, renal failure, nephrotic syndrome, and cirrhosis. GG 11th,
4、2006,陈述其功能，正确。,4,Diuretics are drugs that increase the rate of urine flow and sodium excretion.,利尿药是直接作用于肾小管上皮细胞、增加尿液形成率的物质。,Diuretics are agents that act directly on the tubular epithelial and increased rate of urine formation.,5,Goodman and Gilmans The Pharmacological Basis of Therapeutics, (GG 8t
5、h，1990),利尿药是一类促进钠和水排泄、使尿量增加的药物。,Diuretics are drugs that promote a net loss of sodium (Na+) and water from the body, the net result being an increase in urine flow.,GG 10th, 2001,6,利尿药 用于高血压、心衰、肾衰、肾病综合征和肝硬化等病变时，调节体液的量和/或成份。,Diuretics increase the rate of urine flow and sodium excretion and are used
6、to adjust the volume and/or composition of body fluids in a variety of clinical situations, including hypertension, heart failure, renal failure, nephrotic syndrome, and cirrhosis. GG 11th, 2006,利尿药的适应症,Indications of diureics,临床用于：治疗各种水肿、高血压、尿崩症、肾结石等。,8,本版教科书：,利尿药的适应症,对利尿药作用机制的认识、新的利尿药的研发，均基于对肾脏泌尿生
7、理的了解。,Renal Anatomy and Physiology,9,Na+,channel,Figure 28-5 NaHCO3 reabsorption in proximal tubule. A, antiporter; S, symporter; CH, ion channel. (The actual reaction catalyzed by carbonic anhydrase is OH- + CO2HCO3-; however, H2O OH- + H+, and HCO3- + H+ H2CO3, so the net reaction is H2O + CO2 H2C
8、O3.) Numbers in parentheses indicate stoichiometry. BL and LM indicate basolateral and luminal membranes, respectively.,S, symporter; CH, ion channel. Numbers in parentheses indicate stoichiometry. Designated voltages are the potential differences across the indicated membrane or cell. The mechanism
9、s illustrated here apply to the medullary, cortical, and post macular segments of the thick ascending limb. BL and LM indicate basolateral and luminal membranes, respectively. GG 11th，2006,11,Figure 28-7. NaCl reabsorption in distal convoluted tubule,S, symporter; CH, ion channel. Numbers in parenth
10、eses indicate stoichiometry. BL and LM indicate basolateral and luminal membranes, respectively.,Figure 28-8. Na+ reabsorption in late distal tubule and collecting duct. Cl- reabsorption (not shown) occurs both paracellularly and transcellularly, and the precise mechanism of Cl- transport appears to
11、 be species-specific. A, antiporter; CH, ion channel; CA, carbonic anhydrase. Numbers in parentheses indicate stoichiometry. Designated voltages are the potential differences across the indicated membrane or cell. BL and LM indicate basolateral and luminal membranes, respectively.,AIP, aldosterone-i
12、nduced proteins; ALDO, aldosterone; MR, mineralocorticoid receptor; CH, ion channel; activation of membrane-bound Na+channels; redistribution of Na+ channels from cytosol to membrane; de novo synthesis of Na+ channels; activation of membrane-bound Na+, K+-ATPase; redistri-bution of Na+,K+-ATPase fro
13、m cytosol to membrane; de novo synthesis of Na+,K+-ATPase; changes in permeability of tight junctions; increased mito-chondrial production of ATP. BL and LM indicate basolateral and luminal membranes, respectively.,Figure 28-9. Effects of aldosterone on late distal tubule and collecting duct,Renal A
14、natomy and Physiology,15,Na+,channel,The volume of plasma filtered by the kidney is termed the glomerular rate (GFR) and is equal to approximately 180 L/day for a person weighing 70 kg.,Approximately 125 ml of glomerular ultrafiltrate is formed each minute, yet only 1 ml/min of urine is produced. Th
15、erefore, greater than 99% of the glomerular ultrafiltrate is reabsorbed.,16,1.高效利尿药 high efficacy (ceiling) diuretics 袢利尿药 Loop diuretics 钠钾氯同向转运抑制剂 (Inhibitor of Na+-K+-2Cl- symport),二、利尿药的分类(Classification of diuretics),18,代表药：呋塞米(furosemide) 其它：依他尼酸、布美他尼、阿佐塞米等,2.中效利尿药 moderate efficacy diuretics
16、抑制Na+-Cl- 同向转运(symport)， 也称噻嗪类利尿药 代表药：氢氯噻嗪 非噻嗪类：氯噻酮、吲达帕胺等,19,3.低效利尿药 Low efficacy diuretics 醛固酮拮抗剂(aldosterone antagonist)：螺内酯(speronolactone)、Eplerenon,肾小管上皮细胞Na+通道抑制药 (inhibitors of epithelial Na+ channel)：氨苯蝶啶(triamterene)、阿米洛利(amiloride),碳酸酐酶抑制剂 (inhibitors of carbonic anhydrase)：乙酰唑胺（醋唑磺胺）,注：&:留钾利尿药（K+ sparing diuretics）,20,21,常用利尿药的主要作用部位及机制,21,.高效利尿药 呋塞米(furosemide, 速尿，呋喃苯胺酸） 依他尼酸(etacrynic acid，利尿酸) 已少用 布美他尼(bumetanide，丁苯氧
