利尿药Diuretics的课件

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,*,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的课件,尿的生成和排出,肾小球滤过; 肾小管和集合管的重吸收及分泌,肾小球滤过液(原尿)约180,L/,每天, 尿量12,L.,排出代谢终产物及进入体内的异物,调节细胞外液量和渗透压,维持电解质平衡,机制,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,H,+,+ HCO,3,-,H,2,CO,3,CO,2,+H,2,O,Na,+,乙酰唑胺（弱效）,碳酸酐酶抑制剂,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,2,20,30,50,80,30,40,60,90,100,100,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,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,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】,【临床应用】,水和电解质紊乱:,耳毒性:,高尿酸血症:,【不良反应】,严重水肿：,急性肺水肿和脑水肿：,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,),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。,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,+,*,吸收与分泌受机体平衡状况调节,Ca,2+,Na,+,Ca,2+,K,+,K,+,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：,特点, 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),Thiazides:,抗尿崩症作用:,主要用于肾性尿崩症及加压素无效的尿崩症.,抑制磷酸二酯酶远曲小管和集合管细胞内,cAMP,远曲小管对水的通透性,NaCl,的排出,造成负盐平衡血浆渗透压,减轻口渴干和减少饮水量胞外容量和尿量,.,【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：,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.氯噻嗪 (Chlorothiazide),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,1,Na,+,3,2,4,浓缩,稀释,浓缩,逆流倍增机制,5,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,+,乙酰唑胺（弱效）,碳酸酐酶抑制剂,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,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,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 problems.,Lupus,狼疮.,Gout,痛风,or high risk for developing gout.,月经,期,problems：Potassium-sparing diuretics can make these problems worse.,What else should doctor notice?,Interacting Drugs,Potential Interactions,ACE Inhibitors / K,+,- Sparing Diuretics,Increased hyperkalemia,Cardiac problems (monitor serum K,+,closely),Aminoglycosides /Loop Diuretics,Ototoxicity and nephrotoxicity.(monitor hearing and serum creatinine closely),Digoxin / Thiazide & Loop D.,Hypokalemia,Increased digoxin binding & toxicity. Monitor K,+,and cardiac function),- Blockers /Thiazide Diuretics,Hyperglycemia, hyperlipidemia, hyperuricemia.,Steroids /Thiazide & Loop D.,Increased risk of hypokalemia(monitor K+ closely,),Carbamazepine or Chlorpropamide / Thiazide,Increased risk of hyponatremia (monitor Na,+),Interactions,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:,降压药的联合应用,比较合理的配伍为：,1、ACE-I（或血管紧张素II受体拮抗剂）与利尿药；,2、利尿药与-阻滞剂；,北京降压0号,Beijing Hypotensive No. 0,(复方降压平片),氢氯噻嗪Hydrochlorothiazide: 排钠、钾, 导致低钾,氨苯喋啶Triamterene: 留钾,利眠宁Librium：,镇静、抗焦虑、肌肉松弛。,硫酸双肼屈嗪,Dihydralazine:,松弛小动脉平滑肌,Diastolic BP降低较多；Systolic BP降低较少,利血平 Reserpine:,交感神经节后纤维末梢NE耗竭,Diastolic BP降低较少；Systolic BP降低较多,*,水钠潴流,基础降压药功效相承，互相弥补,利尿药协同降压、提高降压作用，降低基础降压药用药剂量，减轻副作用,镇静药调节中枢神经，缓解症状，辅助降压,降压作用平稳、显著,能明显降低脑卒中及冠心病发病率与死亡率,