21 第二十一章 利尿药和脱水药.ppt

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1、Diuretics and DehydrantsChapter 211 1objective掌掌握握 呋塞塞米米、氢氯噻嗪、螺螺内内酯、氨氨苯苯蝶蝶啶的的药理理作作用用、主主要要不不良良反反应及及药物物的的相相互作用。互作用。熟熟悉悉 利利尿尿药的的概概念念与与分分类，泌泌尿尿生生理理及及药物物作作用用部部位位,脱脱水水药的的概概念念。甘甘露露醇醇的的作作用用、应用及不良反用及不良反应。了解了解 其它利尿其它利尿药、脱水、脱水药的作用特点。的作用特点。2 2High-ceiling diuretics or loop diureticFursosemide 呋塞米呋塞米 ,bumetanide

2、 布美他尼布美他尼 ,Torasemide 特拉塞米特拉塞米 ,etacrynic acid 依他尼酸依他尼酸 THIAZIDESchlorothiazide氯噻嗪氯噻嗪,hydrochlorothiazide 氢氯噻嗪氢氯噻嗪,cyclopenthiazide 环戊甲噻嗪环戊甲噻嗪,bendrofluazide 苄氟噻嗪苄氟噻嗪Potassium-sparing diuretic(保钾类利尿药）保钾类利尿药）Spironolactone 螺内酯螺内酯,triamterene 氨苯蝶啶氨苯蝶啶,Amilorine 阿米洛利阿米洛利 Carbonic anhydrase inhibitorsAc

3、etazolamide 乙酰唑胺乙酰唑胺 3 3 1 Diuretics【definition】acting on kidney excretion of water and electrolyte urine volume Clinical use for edema and unedema diseases.4 4肠系膜上神经节肠系膜上神经节交感神经节交感神经节腹腔神经节腹腔神经节主动脉丛主动脉丛肾丛肾丛肠系膜下神经节肠系膜下神经节5 5肾肾髓髓质质、肾肾皮皮质质、肾肾单单位位6 6【Renal physiology】kidneyNephron肾单位肾单位肾小球肾小球肾小管肾小管近曲小管近

4、曲小管髓袢髓袢远曲小管远曲小管collecting tube集合管集合管glomerular filtration 180L/dfinal urine 1.8L/d99%reabsorption7 7血液流经肾小球血液流经肾小球 滤过而形成原尿。滤过而形成原尿。凡能增加肾血流量凡能增加肾血流量及有效滤过压的药及有效滤过压的药物当可利尿。如氨物当可利尿。如氨茶碱，通过增加心茶碱，通过增加心肌收缩性，增加肾肌收缩性，增加肾血流量及肾小球滤血流量及肾小球滤过率而利尿。但其过率而利尿。但其利尿作用很弱利尿作用很弱。8 89 9Glomerular filtrationCommonly GFR 125m

5、l/min 原尿原尿 125ml60 24=180 L/d 终尿终尿 1.8 L/d 99%reabsorption GFR 10%原尿原尿198L/d;终尿终尿 1.98L/d reabsorption 1%原尿原尿180L/d;终尿终尿 3.6L/d 10101.proximal tubules(近曲小管近曲小管)Reabsorption by:H+-Na+exchangeCO2+H2OCAH+HCO3-Diamox乙酰唑胺乙酰唑胺 H+-Na+exchangeNa+reabsorption urine low efficacy11112.loop of Henle(髓袢髓袢)reabso

6、rption of Na+35%Na+-K+-2Cl-cotransporterfurosemide 稀稀释释浓浓缩缩1212 furosemide 髓袢升支粗段髓袢升支粗段皮皮质部、部、髓髓质部部 Na+-K+-2Cl-cotransporter NaCl reabsorption the dilution and concentration all urine volume;renal PGs synthesis blood stream.1.High efficacy diuretics;2.Na+,K+,Cl-,Ca2+,Mg 2+excretion increase.Notice13

7、133.distal tubules(远曲小管远曲小管)reabsorbs Na+10%(filtrated Na+)By Na+-Cl-cotransporter;impermeable to water;Ca2+reabsorption (parathyroid hormone甲甲 状状 旁旁 腺腺 素素,PTH regulation)1414Thiazides(噻嗪类噻嗪类)acting on the initial part of distal tubule (远曲小管近端）远曲小管近端）Inhibit Na+-Cl-cotransporter NaCl reabsorption th

8、e dilute function;Ca2+reabsorption;tubular lumen Na+Na+-K+exchange Hypokalemia(低血低血钾)moderate efficacy diuretics15154.Collecting tubereabsorbs Na+2%5%(filtrated Na+)by Na+-K+exchange regulated by aldosterone（醛固固酮）;reabsorption of water-urine concentration by ADH(vasopressin)regulation.1616Triamteren

9、e氨苯蝶啶氨苯蝶啶Spironolactone螺内酯螺内酯Na+-K+exchangeantagonize aldosteroneNa+reabsorption，K+excretion1.low efficacy diuretics;2.2.sparing K+Notice1717 Usual drugs 一一.high efficacy diuretics furosemide（呋噻米（呋噻米、速尿速尿）ethacrynic acid（依他尼酸（依他尼酸、利尿酸利尿酸）bumetanide（布美他尼（布美他尼）1818【characteristics】1.Rapidly,strong,sho

10、rtly;2.renal blood flow;3.electrolyte disorders may occur;Na+、Cl-、K+、Ca2+excretion1919Reasons of K+excretion ：1）Na+excretion distal tubule and collecting tubule Na+-K+exchange 2）diuresis blood volume RAAS（+）aldosterone K+excretion Reason of Ca2+excretion:furosemide Ca2+reabsorption2020 Na+-K+-2Cl-共同

11、转运载体蛋白共同转运载体蛋白呋噻米呋噻米管腔膜面管腔膜面（原尿）（原尿）近曲小管近曲小管肾小管上皮细胞肾小管上皮细胞基侧膜面基侧膜面（组织间液）（组织间液）Na+2Cl-（+）Cl-ATPK+Na+K+Ca2+,Mg2+K+K+K+反向扩散反向扩散驱使二价阳驱使二价阳离子重吸收离子重吸收2121【clinical uses】1.Acute pulmonary edema(急性肺水肿急性肺水肿):iv-main indicationfurosemide强利尿利尿血容量血容量回心血量回心血量扩小小A外阻外阻左心左心负荷荷肺水肿改善肺水肿改善Brain edema(脑水水肿)not first ch

12、oice 22222.Other serious edema;cirrhotic ascites(肝硬化腹水肝硬化腹水),CHF,nephrotic edema(肾性水性水肿)3.Acute or chronic renal failure;4.Hypercalemia;5.Expel toxin.2323【adverse reaction】1.Water and electrolyte disturbance Hypovolemia(低血容量低血容量)Hyponatremia(低血低血钠)Hypokalemia(低血低血钾)Hypomeganesemia(低血低血镁)Metabolic al

13、kalosis(代代谢性碱血症性碱血症)Hyperurecemia(高尿酸血症高尿酸血症)24242、Ototoxicity(耳毒性耳毒性)tinnitus(耳耳鸣），），hearing losswith renal insufficiency-more commonnoticeDont used with aminoglycoside（氨基糖苷氨基糖苷类）and cephalosporins(头孢菌素菌素类）3.Other GI reactions;hypersensitive reaction.2525Usual drugs二二.moderate efficacy diuretics -t

14、hiazides(噻嗪类)【common characteristics】1.Sites of action are same;2.Diuretic efficacy(效能效能)are same;3.Have different potency(效价效价强度度).2626hydrochlorothiazide（DCT,氢氯噻嗪)【actions and uses】1.Diuretic action moderate efficacy clinical use for:edema due to CHF;edema of liver disease;nephrotic edema 27272.An

15、tidiuretic action 肾性尿崩症性尿崩症,ADH无效的尿崩症无效的尿崩症.3.hypotensive action early:diureticblood volume Bp;long term used:vasodilation Bp basic antihypertensive drugs (alone or combination with other drugs)2828【adverse reaction】1.Electrolyte disturbanceHypokalemia低钾血;Hyponatremia低钠血症;Hypomagnesemia低镁血症;Metaboli

16、c alkalosis代谢性碱中毒 29292.Metabolism changesHyperuricemia(高尿酸血症高尿酸血症),Hyperglycemia(高血糖高血糖),hyperlipidemia(高血脂高血脂).).3.Hypersensitive reaction cross-irritability with sulfonamide.(交叉交叉过敏性敏性)(磺胺磺胺类)3030Usual drugs三三.Low efficacy diuretics spironolactone(螺内螺内酯)(antisterone 安体舒通安体舒通)its structure similar

17、 to aldosterone,competitive blocks aldosterone receptor sparing K+(保保+）and extruding Na+（排（排Na）3131【characteristics】1.Weaker,slowly,for long time;2.Diuresis depends on aldosterone levels;3.Clinical uses:primary hyperaldosteronism (原原发性性醛固固酮增多症增多症););cirrhosis and nephrotic syndrome (肝硬化和肝硬化和肾病病综合征合征

18、););3232 hypertension and CHF;usually combination with other drugs.4.Long term therapy hyperkalemia(高血高血钾););especially renal function impaired;sexual dysfunction(性激素失性激素失调)3333 Triamterene(氨苯蝶氨苯蝶啶)Amiloride(阿米洛利阿米洛利)act on distal tubule and collecting duct block Na+channel Na+reabsorption luminal n

19、egative electric potential K+secretion .potassium-sparing diuretics Often combine with thiazides or loop diuretics for froward edema(顽固性水固性水肿).).3434四四.Therapeutic principles对因对因治疗治疗卧床卧床休息休息低盐低盐饮食饮食间歇间歇疗法疗法联合联合用药用药35352 Dehydrant agents脱水药 Also called osmotic(渗透性渗透性）diuretics;mannitol 甘露醇甘露醇 sorbito

20、l 山梨醇山梨醇 hypertonic glucose 高渗葡萄糖高渗葡萄糖3636【common characters】1.After iv.inter tissue poorly;2.freely filtered at the glomerulus;3.limited reabsorption by the renal tubule;osmotic pressure of tubular liquid dehydration(脱水作用脱水作用);diuretic action(利尿作用利尿作用)3737 Mannitol【actions uses】1.Dehydration cerebr

21、al edema(脑水水肿)-first choice;glaucoma(青光眼青光眼)(intraocular pressure);2.Diuretic action acute renal failure prevention GFR;renal vasodilation renal blood flow .3838【contraindications】congestive heart failure(CHF);活活动性性颅内出血内出血.others:sorbitol山梨糖醇,hypertonic glucose高渗葡萄糖 393940401 1、Please describe the classes of diuretics,their site of action、mechanism of action、indications and major adverse effects.2 2、Distinguish between diuretics and dehydrants.4141