利尿药-Diuretics

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,利尿药,Diuretics,作用机制,:,离子转运抑制剂,作用环节,:,肾小管与集合管的重吸收,张永鹤,E-mail:,复习肾脏生成尿的生理基础,利尿药的分类、作用特点和作用部位。,利尿药的作用机制、临床应用、不良反应。,学习提要,NaHCO3,NaCl,NaCl,K,+,K,+,Mg,2+,H,2,O,2Cl,-,Ca,2+,Ca,2+,(+PTH),Na,+,NaCl,醛固酮,K,+,H,2,O,(+ADH),H,+,K,+,2Cl,-,Na,+,皮质部,髓质部,近曲小管,髓袢,远曲小管,集,合,管,PTH:,甲状旁腺激素,ADH:,抗利尿激素,肾小管各段功能及利尿药作用部位,H,2,O,5,Na,+,2,1,3,浓缩,稀释,浓缩,逆流倍增机制,4,Na,+,Na,+,逆流交换模式图,H,2,O,H,2,O,H,2,O,H,2,O,Na,+,H,2,O,NaCl,NaCl,NaCl,Na,+,2Cl,-,K,+,皮质,内髓,外髓,H,2,O,NaCl,尿素,尿素,尿素,尿素,浓缩,浓缩,稀释,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,NaHCO3,NaCl,NaCl,K,+,K,+,Mg,2+,H,2,O,2Cl,-,Ca,2+,Ca,2+,(+PTH),Na,+,NaCl,醛固酮,K,+,H,2,O,(+ADH),H,+,K,+,2Cl,-,Na,+,皮质部,髓质部,近曲小管,髓袢,远曲小管,集,合,管,PTH:,甲状旁腺激素,ADH:,抗利尿激素,肾小管各段功能及利尿药作用部位,H,2,O,5,Na,+,2,1,3,浓缩,稀释,浓缩,逆流倍增机制,4,髓袢升支粗段,roximal,convoluted tubule,间液,管腔,肾小管细胞,K,+,2Cl,-,Na,+,Na,+,Cl,-,K,+,K,+,Furosemide,速尿,肾的稀释功能,浓缩功能,Ca,2+,Mg,2+,ATP,35%Na+,重吸收,常用利尿药,袢利尿药,(,高效,),呋塞米,furosemide,(,速尿,呋喃苯胺酸,),口服：,1,小时血药浓度达高峰,【,作用特点,】,迅速，强大，短暂,【,体内过程,】,Decreased,urinary,secretion,Increased,urinary,secretion,Loop diuretics,Na,+,K,+,Ca,+,Volume of urine,【,临床应用,】,水和电解质紊乱,:,低镁血症,耳毒性,:,高尿酸血症,:,【,不良反应,】,严重水肿：急性肺水肿、脑水肿,高钙血症：,高血钾症：,急慢性肾功能衰竭：,高血压危象的辅助治疗,新型降压利尿药,托拉塞米,(,Torasemide,),比利时,Christtiaens,（,Nycomed,）研制,德国贝林格尔曼海姆公司,(1993,年,),用于治疗高血压、心力衰竭、各种水肿及尿崩症等。,特点：,属于髓袢利尿药，利尿作用强大。,具有保钾的特点。,非肾脏清除,国家级化学医药新产品开发指南,第三辑的推荐品种,NaHCO3,NaCl,NaCl,K,+,K,+,Mg,2+,H,2,O,2Cl,-,Ca,2+,Ca,2+,(+PTH),Na,+,NaCl,醛固酮,K,+,H,2,O,(+ADH),H,+,K,+,2Cl,-,Na,+,皮质部,髓质部,近曲小管,髓袢,远曲小管,集,合,管,PTH:,甲状旁腺激素,ADH:,抗利尿激素,肾小管各段功能及利尿药作用部位,H,2,O,5,Na,+,2,1,3,浓缩,稀释,浓缩,逆流倍增机制,4,远曲小管,Distal convoluted tubule,间液,管腔,肾小管细胞,2Cl,-,Na,+,Na,+,Cl,-,K,+,Thiazides,(,中效,):,肾功低下效降低,ATP,重吸收：,Na,+,、,Cl,-,:12%,；,分泌,:K,+,、,H,+,*,吸收与分泌受 甲状旁腺激素,(PTH),和机体平衡状况调节,Ca,2+,Na,+,Ca,2+,K,+,K,+,PTH,Decreased,urinary,secretion,Increased,urinary,secretion,Thiazide,diuretics,Na,+,K,+,Ca,+,Volume of urine,Thiazides,and related agents,A.,氢氯噻嗪,(Hydrochlorothiazide),【,药理作用,】,利尿作用：,温和而持久,;,长期应用可致低血,K,+,;,减少尿,Ca,2+,排出,.,降压作用：降低外周阻力,抗利尿作用,:,尿崩症,:,内分泌代谢障碍,下丘脑,-,垂体受损,-,抗利尿激素,(,antidiuretic,hormone,ADH),分泌减少或缺乏,-,肾小管上皮细胞对,ADH,的敏感性降低,(,即肾源性尿崩症,),【,临床应用,】,1.,水肿,:,1),轻,中度心脏性水肿，注意强心苷中毒,2),肾性水肿：,3),肝硬化腹水：与螺内酯合用。,应注意补,K,+,2,高血压病：,3,尿崩症：特发性高尿钙伴有尿结石者。,低血钾、低血镁、低血钠、低氯性碱血症,高尿酸血和高钙血症,:,3.,抑制胰岛素释放及葡萄糖的利用,;,4.,增加血脂及低密度脂蛋白、胆固醇量,5.,低血容量,【,不良反应及防治,】,【,体内过程,】,口服吸收迅速,1-2,小时起效,.,B.,苄氟噻嗪,(,Bendrofluazide,),氯噻酮,Chlortalidon,氢氯噻嗪,Hydrochlorothiazide,噻嗪类,Thiazides,NaHCO3,NaCl,NaCl,K,+,K,+,Mg,2+,H,2,O,2Cl,-,Ca,2+,Ca,2+,(+PTH),Na,+,NaCl,醛固酮,K,+,H,2,O,(+ADH),H,+,K,+,2Cl,-,Na,+,皮质部,髓质部,近曲小管,髓袢,远曲小管,集,合,管,PTH:,甲状旁腺激素,ADH:,抗利尿激素,肾小管各段功能及利尿药作用部位,H,2,O,5,Na,+,2,1,3,浓缩,稀释,浓缩,逆流倍增机制,4,抗醛固酮利尿药,(,Antisterone,),螺内酯,(,排钠留钾,),醛固酮,Potassium-sparing diuretics(,低效,),A.,螺内酯,(,Spironolactone,antisterone,),Decreased,urinary,secretion,Increased,urinary,secretion,Potassium-sparing diuretics,Na,+,K,+,Ca,+,Volume of urine,2.Actions:,留钾利尿,.,3.Therapeutic uses:,与醛固酮升高有关的水肿,.,4.Adverse effects:,低钠血症、高钾血症,Mechanism:,竞争醛固酮受体,NaHCO3,NaCl,NaCl,K,+,K,+,Mg,2+,H,2,O,2Cl,-,Ca,2+,Ca,2+,(+PTH),Na,+,NaCl,醛固酮,K,+,H,2,O,(+ADH),H,+,K,+,2Cl,-,Na,+,皮质部,髓质部,近曲小管,髓袢,远曲小管,集,合,管,PTH:,甲状旁腺激素,ADH:,抗利尿激素,肾小管各段功能及利尿药作用部位,H,2,O,5,Na,+,2,1,3,浓缩,稀释,浓缩,逆流倍增机制,4,B.,氨苯蝶啶及阿米洛利,Triamterene,and,amiloride,阿米洛利,氨苯蝶啶,H,+,+HCO,3,-,H,2,CO,3,CO,2,+H,2,O,Na,+,HCO,3,-,+H,+,H,2,CO,3,H,2,O+CO,2,Na,+,Na,+,Blood,Lumen,HCO,3,-,近曲小管,Proximal convoluted tubule,CA,CA,重吸收：,Na,+,、,Cl,-,、,K,+,、,H,2,O,：,65%,；,HCO,3,-,：,85%,；,Glucose,、,aa,：,100%,CA,:Carbonic,anhydrase,肾小管上皮细胞,CO,2,ATP,Na,+,K,+,乙酰唑胺（弱效）,碳酸酐酶抑制剂,碳酸酐酶,:,分布,:,眼睛睫状体上皮细胞、肾脏肾小管上皮细胞、胃粘膜上皮细胞和大脑细胞等,.,抑制眼睫状体上皮细胞中碳酸酐酶的活性,抑制大脑细胞中碳酸酐酶的活性,抑制胃粘膜上皮细胞碳酸酐酶的活性,乙酰唑胺,:,分子克隆,Peter,Agre,分布：肾、汗腺、脑脉络膜丛、唾液腺、肺,支气管、生殖系统、眼前房,AQPs,：,10,种亚型,AQP1,：近曲小管和髓袢降支细段上皮细胞顶质膜,AQP2,：集合管上皮细胞,功能的异常,肾源性尿崩症,水通道（,water channel,）蛋白,水孔蛋白（,aquaporin,AQP,）,The function of,vassopressin,on water transportation in the collection duct by AQP water channels.,Summary of relative changes in urinary composition induced by diuretic drugs,Decrease,Increased,Decreased,Increase,Na,+,K,+,Ca,+,HCO,3,-,Na,+,K,+,Ca,+,Volume of urine,Volume of urine,Na,+,K,+,Ca,+,Volume of urine,Na,+,K,+,Ca,+,Volume of urine,Loop diuretics,Acetazolamide,Potassium-sparing diuretics,Thiazide,diuretics,Volume of urine,Ca,+,excretion,K,+,excretion,Na,+,excretion,乙酰唑胺,Acetazolamide,袢利尿药,Loop Diuretics,噻嗪类利尿药,Thiazide,diuretics,留钾利尿药,K,+,-Sparing diuretics,Summary of relative changes in urinary composition induced by diuretic drugs,Decrease,Increased,Decreased,Increase,消除水肿的方法：,1.,对因治疗：去除病因,.,2.,减少钠盐摄入：低盐或无盐膳食,.,3.,采用利尿药抑制肾小管对钠的再吸收,.,4.,补充蛋白质，提高血浆胶体渗透压,.,一、心脏性水肿：强心甙为主要治疗药物；,氢氯噻嗪,:,辅助治疗,急性左心衰所致肺水肿：合用高效利尿药,右心衰：回心血量减少，心室充盈压下降,严重心衰：注意代谢性碱中毒,低血钾：强心苷中毒，与留钾利尿药,利尿药的临床应用,二、肾性水肿：,肾炎、慢性肾炎及肾病综合征：,限盐，限水,噻嗪类加留钾利尿药,急性肾衰早期及慢性肾衰：高效利尿药；,三、肝性水肿：,肝硬化,:,高效利尿药易引起电解质紊乱,加速肝衰竭和诱,发肝昏迷,.,一般先单用留钾利尿药或与噻嗪类利尿药合用,长期应用：心律失常、动脉硬化、冠心病,脑中风、,肠癌和糖尿病等。,缺镁、钾是导致心律失常的主要原因,利尿药所致低血钾时，往往同时伴有低血镁，倘若单纯补钾不能纠正低血钾时，补镁（静注硫酸镁）后则易于纠正。,利尿药的潜在危险,Allergies to other medicines.,Pregnant,or breast feeding baby.,Diabetes.dehydrated easily.,Pancreatitis,医,胰腺炎,.,Kidney pro