DiureticsandDehydrants利尿藥和脫水藥Chapter211第二十一章利尿藥和脫水藥objective掌握

呋塞米、氫氯噻嗪、螺內(nèi)酯、氨苯蝶啶的藥理作用、主要不良反應(yīng)及藥物的相互作用。熟悉利尿藥的概念與分類，泌尿生理及藥物作用部位,脫水藥的概念。甘露醇的作用、應(yīng)用及不良反應(yīng)。。了解其它利尿藥、脫水藥的作用特點(diǎn)。2第二十一章利尿藥和脫水藥High-ceilingdiureticsorloopdiureticFursosemide呋塞米,bumetanide布美他尼,Torasemide特拉塞米,etacrynicacid依他尼酸

THIAZIDESchlorothiazide氯噻嗪,hydrochlorothiazide

氫氯噻嗪,cyclopenthiazide環(huán)戊甲噻嗪,bendrofluazide芐氟噻嗪Potassium-sparingdiuretic(保鉀類利尿藥）Spironolactone

螺內(nèi)酯,triamterene氨苯蝶啶,

Amilorine

阿米洛利CarbonicanhydraseinhibitorsAcetazolamide乙酰唑胺

3第二十一章利尿藥和脫水藥§1Diuretics【definition】actingonkidney→excretionofwaterandelectrolyte↑→urinevolume↑

Clinicalusefor

edemaandunedemadiseases.4第二十一章利尿藥和脫水藥腸系膜上神經(jīng)節(jié)交感神經(jīng)節(jié)腹腔神經(jīng)節(jié)主動脈叢腎叢腸系膜下神經(jīng)節(jié)5第二十一章利尿藥和脫水藥腎髓質(zhì)、腎皮質(zhì)、腎單位6第二十一章利尿藥和脫水藥【Renalphysiology】kidneyNephron腎單位腎小球腎小管近曲小管髓袢遠(yuǎn)曲小管collectingtube集合管glomerularfiltration180L/dfinalurine1.8L/d99%reabsorption7第二十一章利尿藥和脫水藥血液流經(jīng)腎小球?yàn)V過而形成原尿。凡能增加腎血流量及有效濾過壓的藥物當(dāng)可利尿。如氨茶堿，通過增加心肌收縮性，增加腎血流量及腎小球?yàn)V過率而利尿。但其利尿作用很弱。8第二十一章利尿藥和脫水藥9第二十一章利尿藥和脫水藥GlomerularfiltrationCommonlyGFR125ml/min

原尿125ml×60×24=180L/d

終尿1.8L/d

99%reabsorption↑GFR10%

原尿198L/d;終尿

1.98L/d

↓reabsorption1%

原尿180L/d;終尿

3.6L/d

10第二十一章利尿藥和脫水藥1.proximaltubules

(近曲小管

)Reabsorptionby:H+-Na+exchangeCO2+H2OCAH++HCO3

-Diamox乙酰唑胺

㈠H+-Na+exchange↓Na+reabsorption↓→urine↑lowefficacy11第二十一章利尿藥和脫水藥2.loopofHenle

(髓袢)reabsorptionofNa+

≈35%

Na+-K+-2Cl-

cotransporterfurosemide㈠稀釋濃縮12第二十一章利尿藥和脫水藥★

furosemide

㈠髓袢升支粗段皮質(zhì)部、髓質(zhì)部

Na+-K+-2Cl-cotransporter→NaClreabsorption↓→thedilutionandconcentrationall↓→urinevolume↑;★↑renalPGssynthesis→bloodstream↑.1.Highefficacydiuretics;2.Na+,K+,Cl-,Ca2+,Mg2+excretionincrease.Notice13第二十一章利尿藥和脫水藥3.distaltubules(遠(yuǎn)曲小管)reabsorbsNa+≈10%(filtratedNa+)ByNa+-Cl-cotransporter;

impermeabletowater;

Ca2+reabsorption(parathyroidhormone甲狀旁腺素,PTHregulation)14第二十一章利尿藥和脫水藥Thiazides

(噻嗪類)

actingon

theinitialpartofdistaltubule

(遠(yuǎn)曲小管近端）

InhibitNa+-Cl-cotransporter

NaClreabsorption

thedilutefunction↓;

Ca2+reabsorption;

tubularlumen[Na+]

Na+-K+exchangeHypokalemia(低血鉀)moderateefficacydiuretics15第二十一章利尿藥和脫水藥4.CollectingtubereabsorbsNa+2%~5%(filtratedNa+)byNa+-K+exchangeregulatedbyaldosterone（醛固酮）;reabsorptionofwater----urineconcentrationbyADH(vasopressin)regulation.16第二十一章利尿藥和脫水藥Triamterene氨苯蝶啶Spironolactone螺內(nèi)酯㈠Na+-K+exchangeantagonizealdosteroneNa+reabsorption↓，K+excretion↓lowefficacydiuretics;2.sparingK+

Notice17第二十一章利尿藥和脫水藥

Usualdrugs

一.highefficacydiuretics

furosemide

（呋噻米、速尿）

ethacrynicacid

（依他尼酸、利尿酸）

bumetanide

（布美他尼）18第二十一章利尿藥和脫水藥【characteristics】

1.Rapidly,strong,shortly;

2.

renalbloodflow;3.electrolytedisordersmayoccur;

Na+、Cl-、K+、Ca2+excretion↑19第二十一章利尿藥和脫水藥ReasonsofK+excretion↑

：

1）Na+excretion↑→distaltubule

andcollectingtubuleNa+-K+

exchange↑2）diuresis→blood

volume↓→RAAS（+）

→aldosterone↑→K+excretion↑ReasonofCa2+excretion↑:

furosemide

→㈠

Ca2+reabsorption20第二十一章利尿藥和脫水藥

Na+-K+-2Cl-共同轉(zhuǎn)運(yùn)載體蛋白呋噻米管腔膜面（原尿）近曲小管腎小管上皮細(xì)胞基側(cè)膜面（組織間液）Na+2Cl-（+）Cl-ATPK+Na+K+Ca2+,Mg2+K+K+K+反向擴(kuò)散驅(qū)使二價陽離子重吸收21第二十一章利尿藥和脫水藥【clinicaluses】

1.Acutepulmonaryedema

(急性肺水腫):

iv-mainindicationfurosemide強(qiáng)利尿→血容量↓→回心血量↓擴(kuò)小A→外阻↓→左心負(fù)荷↓肺水腫改善Brainedema(腦水腫)

notfirstchoice

22第二十一章利尿藥和脫水藥2.Otherseriousedema;

cirrhoticascites(肝硬化腹水),CHF,nephroticedema(腎性水腫)3.Acuteorchronicrenalfailure;4.Hypercalemia;5.Expeltoxin.23第二十一章利尿藥和脫水藥【adversereaction】1.Waterandelectrolytedisturbance

Hypovolemia(低血容量)

Hyponatremia(低血鈉)

Hypokalemia(低血鉀)

Hypomeganesemia(低血鎂)Metabolicalkalosis(代謝性堿血癥)

Hyperurecemia(高尿酸血癥)24第二十一章利尿藥和脫水藥2、Ototoxicity

(耳毒性)

tinnitus(耳鳴），hearingloss……

with

renalinsufficiency-----morecommonnoticeDon’tusedwith

aminoglycoside（氨基糖苷類）andcephalosporins(頭孢菌素類）

3.OtherGIreactions;hypersensitivereaction….25第二十一章利尿藥和脫水藥Usualdrugs二.moderateefficacydiuretics----thiazides

(噻嗪類)【commoncharacteristics】

1.

Sitesofactionaresame;

2.

Diureticefficacy(效能)

aresame;

3.

Have

differentpotency(效價強(qiáng)度).26第二十一章利尿藥和脫水藥hydrochlorothiazide（DCT,氫氯噻嗪)【actionsanduses】

1.Diureticaction

moderateefficacy

clinicalusefor:

edemaduetoCHF;edemaofliverdisease;nephroticedema…

27第二十一章利尿藥和脫水藥2.Antidiureticaction

腎性尿崩癥,ADH無效的尿崩癥.3.hypotensiveactionearly:diuretic→bloodvolume↓→Bp↓;

longtermused:vasodilation→Bp↓

basicantihypertensivedrugs

(aloneorcombinationwithotherdrugs)28第二十一章利尿藥和脫水藥【adversereaction】

1.Electrolytedisturbance

Hypokalemia低鉀血;Hyponatremia低鈉血癥;Hypomagnesemia低鎂血癥;Metabolicalkalosis代謝性堿中毒…

29第二十一章利尿藥和脫水藥2.Metabolismchanges

Hyperuricemia(高尿酸血癥),

Hyperglycemia(高血糖),

hyperlipidemia(高血脂).Hypersensitivereaction

cross-irritabilitywithsulfonamide.(交叉過敏性)(磺胺類)30第二十一章利尿藥和脫水藥Usualdrugs三.Lowefficacydiureticsspironolactone(螺內(nèi)酯)

(antisterone安體舒通)itsstructuresimilartoaldosterone,

competitiveblocksaldosteronereceptor

sparingK+(保Ｋ+）andextrudingNa+（排Na）

31第二十一章利尿藥和脫水藥【characteristics】Weaker,slowly,forlongtime;Diuresisdependsonaldosteronelevels;Clinicaluses:primaryhyperaldosteronism

(原發(fā)性醛固酮增多癥);

cirrhosisandnephroticsyndrome

(肝硬化和腎病綜合征);32第二十一章利尿藥和脫水藥

hypertensionandCHF;usuallycombinationwithotherdrugs.Longtermtherapy

hyperkalemia(高血鉀);

especially

renalfunctionimpaired;sexualdysfunction(性激素失調(diào))…33第二十一章利尿藥和脫水藥

Triamterene(氨苯蝶啶)

Amiloride

(阿米洛利)

actondistaltubuleandcollectingduct

blockNa+channel

Na+reabsorptionluminalnegativeelectricpotentialK+secretion.

potassium-

sparingdiuretics

Oftencombinewiththiazidesorloopdiuretics

forfrowardedema(頑固性水腫).34第二十一章利尿藥和脫水藥Therapeuticprinciples對因治療臥床休息低鹽飲食間歇療法聯(lián)合用藥35第二十一章利尿藥和脫水藥§2

Dehydrantagents脫水藥Also

called

osmotic

(滲透性）diuretics;

mannitol

甘露醇sorbitol

山梨醇hypertonicglucose高滲葡萄糖36第二十一章利尿藥和脫水藥【commoncharacters】

1.Afteriv.intertissuepoorly;2.freelyfilteredattheglomerulus;3.limitedreabsorption