藥物對(duì)腎臟的影響課件

Kidney

and

Drugs

腎臟與藥物KidneyandDrugs

腎臟與藥物Kidney,Drugs,andMedication

MiscellaneoustalksaboutdrugsandthekidneysUnderstandhowadrugisconnectedwiththekidneyandthewholebodyKidney,Drugs,andMedication

KidneyandMedicationKnowtheactionsiteofdiureticsUnderstandtheroleofthekidneyintheactionandmetabolismofcommonlyuseddrugsUnderstandtheantibioticdistribution,eliminationanddrugchoicesKnowthecommondrug-relatedrenaldamageKnowtheroleofthekidneyinbloodpressurecontrol,pharmacologyofantihypertensivedrugswhichactthroughorrelatedwiththekidneyandclinicaluse

KidneyandMedicationKnowthDiuretics,osmoticdiuretics

Thiazides,Loopdiuretics,K+-sparingdiuretics

mannitol

利尿藥與滲透性利尿藥:噻嗪類

袢利尿劑保鉀利尿劑

甘露醇CollectingtubuleThiazidesInhibitactiveexchangeofCl-NainthecorticaldilutingsegmentoftheascendingloopofHenleK+-sparingInhibitreabsorptionofNainthedistalconvolutedandcollectingtubuleLoopdiureticsInhibitexchangeofCl-Na-KinthethicksegmentoftheascendingloopofHenlemannitolmannitolmannitolmannitolmannitolmannitolmannitolDiuretics,osmoticdiuretics

T

Hematuria?

Hematuria?

Renaleliminationofendogenousmetabolites

andforeign

substancesEndogenousmetabolicproducts&foreignsubstanceseliminatedbythekidneys:UreafromaminoacidmetabolismUricacidfromnucleicacidsCreatininefrommusclesEndproductsofhemoglobinmetabolismHormones&theirmetabolitesForeignsubstances(e.g.,drugs,pesticides,&otherchemicalsingestedinthefood)

Renaleliminationofendogeno

Rifampin利福平Upto30%ofadoseofthedrugisexcretedintheurineand60%to65%inthefeces;lessthanhalfofthismaybeunalteredantibiotic.Adjustmentofdosageisnotnecessaryinpatientswithimpairedrenalfunction.

Rifampinisdistributedthroughoutthebodyandispresentineffectiveconcentrationsinmanyorgansandbodyfluids,includingtheCSF.Thisisperhapsbestexemplifiedbythefactthatthedrugmayimpartanorange-redcolortotheurine,feces,saliva,sputum,tears,andsweat;patientsshouldbesowarned.告知患者Patienturinesample應(yīng)預(yù)先告知患者

Rifampin利福平Upto30%ofado

UnderstandhowadrugisconnectedwiththekidneysandothersystemsaswellasotherdrugsKnowtheurinarysystemFunctionalanatomyConnectionwithothersystemsRoleindrugmetabolismKnowthedrugpharmacologyMetabolismActionApplicationUnwantedeffectKnowthewayofconnectingpharmacologywiththekidneyisimportanttothecareandattendingofapatient

UnderstandhowadrugisconnPyelonephritisandMedication

Acommonandtreatableinfectiousdisease

腎盂腎炎是一種常見(jiàn)的感染性疾病Ascendingurinarytract

infection逆行尿路感染Effectiveantibactericidalmedicationisimportantaswellaseliminationofinfectionsource.消除導(dǎo)致感染的原因大多數(shù)腎臟疾病是可治療和可治愈的PyelonephritisandMedication

Antibiotics抗生素:distribution,eliminationanddrugchoicesAntimicrobialsthatappearinhighconcentrationsinurineoreliminatedmainlythroughthekidneys:Aminoglycosides氨基糖苷類effectiveforurinaryinfectionbutwithunwantedeffects,tendtoresultinrenaldysfunctioninoldpatientsandpatientswithrenaldamagePenicillins,someβ-lactamantibiotics青霉素類與β內(nèi)酰胺類eliminatedintheurineandarethedrugsofchoicewithsensitivebacteriainfectionQuinolones

喹諾酮類lesssideeffects,effectiveforinfectionofthemostorgansandtissuesespeciallytheurinaryandthelungRifampin

利福平

Antibiotics抗生素:distribution,Howthe

kidneyisconnectedwiththeothersystemsThekidneyisintimatelyconnectedwiththecirculationsystembymanywaysAnatomyconnectionFunctionalconnectionDiseaseconnectionMedicationconnectionTakingrifampinasanexampleHowthekidneyisconnectedwi

Rifampinis

ahepaticmicrosomalenzymeinducer利福平為肝藥酶誘導(dǎo)劑Followingabsorptionfromthegastrointestinaltract,rifampiniseliminatedrapidlyinthebile,andanenterohepaticcirculationensues.Duringthistime,thedrugisprogressivelydeacetylated,suchthatafter6hours,nearlyalloftheantibioticinthebileisinthedeacetylatedform,whichretainsessentiallyfullantibacterialactivity.Thehalf-lifeofrifampinvariesfrom1.5to5hoursandisincreasedbyhepaticdysfunction.Thehalf-lifeofrifampinisprogressivelyshortenedbyabout40%duringthefirst14daysoftreatment,owingtoinductionofhepaticmicrosomalenzymesthatacceleraterifampindeacetylation.

RifampinisahepaticmicrosoIfthepatientwithchronickidneydiseasewhoseBPisundercontrolonantihypertensivemedication(amloidipine,bisoprolol)reportspoorbloodpressurewhenhebegintotakerifampinforlungtuberculosis,whatwouldyouconsider?Rifampinenhancesthelivermetabolismofantihypertensiveagents,whichleadstoshortenthet1/2ofantihypertensivesandweakentheirBPloweringeffects.Theresultingelevatedpressuremayfurtheracceleraterenaldysfunction.Doesrifampinimpairrenalfunction?-Yes，interstitialnephritisCombinedMedicationCase

Knowhowadrugisconnected

withthekidneyandotherdrugsIfthepatientwithchronicki

Thedrug-relatedrenaldamage

Antimicrobials&

Cyclosporine

抗微生物藥與環(huán)孢素的腎損害Aminoglycosides氨基糖苷類

RenaldamageincludingtubularandglomerulartoxicitySulfonamides磺胺類Crystalformationinthetubule腎小管內(nèi)結(jié)晶損害Rifampin

利福平InterstitialnephritisVancomycin萬(wàn)古霉素InterstitialnephritisCyclosporine環(huán)孢素Nephrotoxicityoccursinthemajorityofpatientstreatedwithcyclosporine.(Hypertensionisalsofrequentlyseen.)Shouldbeavoidedinpatientswithreducedrenalfunction.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Sulfonamides磺胺類腎損害DisturbancesoftheurinarytractbysulfonamidesAlthoughtheriskofcrystalluriawasrelativelyhighwiththeolder,lesssolublesulfonamides,theincidenceofthisproblemisverylowwithmoresolubleagentssuchassulfisoxazole.Crystalluriahasoccurredindehydratedpatientswiththeacquiredimmunedeficiencysyndrome(AIDS)whowerereceivingsulfadiazineforToxoplasmaencephalitis.Fluidintakeshouldbesufficienttoensureadailyurinevolumeofatleast1200ml(inadults).AlkalinizationoftheurinemaybedesirableifurinevolumeorpHisunusuallylowbecausethesolubilityofsulfisoxazoleincreasesgreatlywithslightelevationsofpH.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷類腎損害Approximately8%to26%ofpatientswhoreceiveanaminoglycosideformorethanseveraldayswilldevelopmildrenalimpairmentthatisalmostalwaysreversible.Theelderlyandpatientswithunderlyingrenaldiseasearepronetotheaminoglycosiderenaldamage.Thetoxicityresultsfromaccumulationandretentionofaminoglycosideintheproximaltubularcells.Theinitialmanifestationofdamageatthissiteisexcretionofenzymesoftherenaltubularbrushborder.Afterseveraldays,thereisadefectinrenalconcentratingability,mildproteinuria,andtheappearanceofhyalineandgranularcasts.Theglomerularfiltrationrateisreducedafterseveraladditionaldays.Thenonoliguricphaseofrenalinsufficiencyisthoughttobeduetotheeffectsofaminoglycosidesonthedistalportionofthenephronwithareducedsensitivityofthecollecting-ductepitheliumtoendogenousantidiuretichormone.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷類腎損害Whilesevereacutetubularnecrosismayoccurrarely,themostcommonsignificantfindingisamildriseinplasmacreatinine.Theimpairmentinrenalfunctionisalmostalwaysreversiblebecausetheproximaltubularcellshavethecapacitytoregenerate.

ThemechanismofrenaldamageThebiochemicaleventsleadingtotubularcelldamageandglomerulardysfunctionarepoorlyunderstoodbutmayinvolveperturbationsofthestructureofcellularmembranes.Aminoglycosidesinhibitvariousphospholipases,sphingomyelinases,andATPases,andtheyalterthefunctionofmitochondriaandribosomes.Becauseoftheabilityofcationicaminoglycosidestointeractwithanionicphospholipids,thesedrugsmayimpairthesynthesisofmembrane-derivedautacoidsandintracellularsecondmessengerssuchasprostaglandins,inositolphosphates,anddiacylglycerol.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷類腎損害Derangementsofprostaglandinmetabolismmayexplaintherelationshipbetweentubulardamageandreductioninglomerularfiltrationrate.Othershaveobservedmorphologicalchangesinglomerularendothelialcells(decreasednumberofendothelialfenestrations)andreductionintheglomerularcapillaryultrafiltrationcoefficientinanimalsreceivingaminoglycosides.Ca2+hasbeenshowntoinhibittheuptakeandbindingofaminoglycosidestotherenalbrush-borderluminalmembraneinvitro,andsupplementarydietaryCa2+attenuatesexperimentalnephrotoxicity.Aminoglycosideseventuallyareinternalizedbypinocytosis.Morphologically,thereisclearevidenceofaccumulationofdruginliposomes,ameansbywhichaminoglycosidesaretrapped,concentrated(upto50timestheplasmaconcentration),andpreparedforextrusionintotheurineasmultilamellarphospholipidstructurescalledmyeloidbodies.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

ACEIsandARBsACEIs及ARBs腎損害

ACEIsandARBsPatientswithseverebilateralrenalarterystenosispredictablydeveloprenalfailureonACEIs,becauseglomerularfiltrationisnormallymaintained,inthefaceoflowafferentarteriolarpressure,byangiotensinII,whichselectivelyconstrictsefferentarterioles;hyperkalaemiamaybesevereowingtoreducedaldosteronesecretion.SuchrenalfailureisreversibleprovidedthatitisrecognisedpromptlyandtreatmentwithACEIdiscontinued.ACEIsandARBsarenotrecommendedtousesimultaneouslyinpatientswithrenaldysfunction.腎功能障礙者建議避免使用ACEIs及ARBs

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

AspirinAspirin阿司匹林Saltandwaterretention

Edema,worseningofrenalfunctioninrenal/cardiacpatientsDecreasedeffectivenessofantihypertensivesDecreasedeffectivenessofdiuretics

DecreasedurateexcretionHyperkalemiaUseoflong-termaspirin(asanantipletemedication)shouldbecautiousinpatientswithrenaldisease

Thedrug-relatedrenaldamageProstaglandins

(PGE2andPGI2)

aslocalvasodilators前列腺素是腎臟內(nèi)源性保護(hù)因素Prostaglandins(PGE2andPGI2)：actaslocalvasodilators,areproducedinresponsetosympatheticstimulationandAngII腎臟局部擴(kuò)血管的前列腺素系統(tǒng)對(duì)交感興奮及血管緊張素II具有一定的拮抗作用NSAIDsinhibitprostaglandinbiosynthesis.Sinceprostaglandinsareoneofthefactorsthatcounteracttheconstrictionofrenalarterioles,especiallyafferentarterioles,NSAIDsmaybedetrimentaltothekidneybloodflow,leadingtoacuteischemicrenalfailure.非甾體類抗炎藥抑制腎臟前列腺素的生成可能減少腎血流導(dǎo)致腎臟缺血Itisespeciallysoinpatientswithheartfailureandliverdisease,glomerularfiltrationdependcriticallyonprostaglandinbiosynthesis.Prostaglandins(PGE2andPGI2)Vasculardisordersofthekidneyandantihypertensives腎血管疾病與抗高血壓藥ACEIsandARBs-Acase一個(gè)臨床案例Cardiaccatheterization心導(dǎo)管檢查revealednormalcoronaryarteriesinanelderlypatientwithheartfailure,butafterinitiationoftherapywithanACEIandspironolactone,progressivekidneydiseasewithhyperkalemiaandpoorbloodpressurecontrolensued.開(kāi)始用ACEI及螺內(nèi)酯后出現(xiàn)進(jìn)展性腎功能障礙、高血鉀，高血壓難以控制

RenalDopplerultrasonographysuggestedbilateralrenalarterystenosis,asconfirmedbyangiography.多普勒血流顯示雙側(cè)腎動(dòng)脈狹窄，血管造影證實(shí)Thepatientunderwentsuccessfulpercutaneous經(jīng)皮revascularizationinstagesleadingtoareturntonormalleftventricularfunctionandimprovedbloodpressurecontrol.血管成形術(shù)后心衰及血壓得到改善VasculardisordersofthekidnVasculardisordersofthekidneyandantihypertensives腎血管疾病與抗高血壓藥ACEIsandARBs-AcaseCardiaccatheterizationrevealednormalcoronaryarteriesinanelderlypatientwithheartfailure,butafterinitiationoftherapywithanACEIandspironolactone,progressivekidneydiseasewithhyperkalemiaandpoorbloodpressurecontrolensued.RenalDopplerultrasonographysuggestedbilateralrenalarterystenosis,asconfirmedbyangiography.Thepatientunderwentsuccessfulpercutaneousrevascularizationinstagesleadingtoareturntonormalleftventricularfunctionandimprovedbloodpressurecontrol.VasculardisordersofthekidnRAASblockadeandglomerular

filtrationRAAS阻斷與腎小球?yàn)V過(guò)EffectsofACEIsandARBsonglomerularfiltrationAngII收縮出球小動(dòng)脈為主，維持正常GFRSinceAngIIcontractstheefferentarteriolemorethantheafferentarterioles,overdilationofefferentarteriolecanreduceglomerularfiltrationpressureandthusglomerularfiltrationrate.AngII對(duì)出球小動(dòng)脈收縮強(qiáng)于入球小動(dòng)脈，過(guò)度擴(kuò)張出球小動(dòng)脈降低腎小球?yàn)V過(guò)壓入出球小動(dòng)脈出球小動(dòng)脈AngII收縮出球小動(dòng)脈為主腎小球毛細(xì)血管內(nèi)平均壓60mmHgRAASblockadeandglomerular

Roleofthekidneyincontrollingbloodpressureandthepharmacologyofantihypertensivedrugs見(jiàn)另附幻燈RoleofthekidneyincontrollIodinecontrastagent-inducednephropathy含碘造影劑性腎病請(qǐng)同學(xué)們檢索一下現(xiàn)代醫(yī)療中含碘造影劑使用現(xiàn)狀與腎臟損害的情況：含碘造影劑是藥物么？含碘造影劑可對(duì)腎臟產(chǎn)生什么樣的不良反應(yīng)？如何預(yù)防這些造影劑的不良反應(yīng)？Iodinecontrastagent-induced謝謝！請(qǐng)關(guān)注腎臟保護(hù)減少損害腎臟的因素請(qǐng)關(guān)注腎臟疾病的綜合預(yù)防與治療

謝謝！請(qǐng)關(guān)注腎臟保護(hù)減少損害腎臟的因素Kidney

and

Drugs

腎臟與藥物KidneyandDrugs

腎臟與藥物Kidney,Drugs,andMedication

MiscellaneoustalksaboutdrugsandthekidneysUnderstandhowadrugisconnectedwiththekidneyandthewholebodyKidney,Drugs,andMedication

KidneyandMedicationKnowtheactionsiteofdiureticsUnderstandtheroleofthekidneyintheactionandmetabolismofcommonlyuseddrugsUnderstandtheantibioticdistribution,eliminationanddrugchoicesKnowthecommondrug-relatedrenaldamageKnowtheroleofthekidneyinbloodpressurecontrol,pharmacologyofantihypertensivedrugswhichactthroughorrelatedwiththekidneyandclinicaluse

KidneyandMedicationKnowthDiuretics,osmoticdiuretics

Thiazides,Loopdiuretics,K+-sparingdiuretics

mannitol

利尿藥與滲透性利尿藥:噻嗪類

袢利尿劑保鉀利尿劑

甘露醇CollectingtubuleThiazidesInhibitactiveexchangeofCl-NainthecorticaldilutingsegmentoftheascendingloopofHenleK+-sparingInhibitreabsorptionofNainthedistalconvolutedandcollectingtubuleLoopdiureticsInhibitexchangeofCl-Na-KinthethicksegmentoftheascendingloopofHenlemannitolmannitolmannitolmannitolmannitolmannitolmannitolDiuretics,osmoticdiuretics

T

Hematuria?

Hematuria?

Renaleliminationofendogenousmetabolites

andforeign

substancesEndogenousmetabolicproducts&foreignsubstanceseliminatedbythekidneys:UreafromaminoacidmetabolismUricacidfromnucleicacidsCreatininefrommusclesEndproductsofhemoglobinmetabolismHormones&theirmetabolitesForeignsubstances(e.g.,drugs,pesticides,&otherchemicalsingestedinthefood)

Renaleliminationofendogeno

Rifampin利福平Upto30%ofadoseofthedrugisexcretedintheurineand60%to65%inthefeces;lessthanhalfofthismaybeunalteredantibiotic.Adjustmentofdosageisnotnecessaryinpatientswithimpairedrenalfunction.

Rifampinisdistributedthroughoutthebodyandispresentineffectiveconcentrationsinmanyorgansandbodyfluids,includingtheCSF.Thisisperhapsbestexemplifiedbythefactthatthedrugmayimpartanorange-redcolortotheurine,feces,saliva,sputum,tears,andsweat;patientsshouldbesowarned.告知患者Patienturinesample應(yīng)預(yù)先告知患者

Rifampin利福平Upto30%ofado

UnderstandhowadrugisconnectedwiththekidneysandothersystemsaswellasotherdrugsKnowtheurinarysystemFunctionalanatomyConnectionwithothersystemsRoleindrugmetabolismKnowthedrugpharmacologyMetabolismActionApplicationUnwantedeffectKnowthewayofconnectingpharmacologywiththekidneyisimportanttothecareandattendingofapatient

UnderstandhowadrugisconnPyelonephritisandMedication

Acommonandtreatableinfectiousdisease

腎盂腎炎是一種常見(jiàn)的感染性疾病Ascendingurinarytract

infection逆行尿路感染Effectiveantibactericidalmedicationisimportantaswellaseliminationofinfectionsource.消除導(dǎo)致感染的原因大多數(shù)腎臟疾病是可治療和可治愈的PyelonephritisandMedication

Antibiotics抗生素:distribution,eliminationanddrugchoicesAntimicrobialsthatappearinhighconcentrationsinurineoreliminatedmainlythroughthekidneys:Aminoglycosides氨基糖苷類effectiveforurinaryinfectionbutwithunwantedeffects,tendtoresultinrenaldysfunctioninoldpatientsandpatientswithrenaldamagePenicillins,someβ-lactamantibiotics青霉素類與β內(nèi)酰胺類eliminatedintheurineandarethedrugsofchoicewithsensitivebacteriainfectionQuinolones

喹諾酮類lesssideeffects,effectiveforinfectionofthemostorgansandtissuesespeciallytheurinaryandthelungRifampin

利福平

Antibiotics抗生素:distribution,Howthe

kidneyisconnectedwiththeothersystemsThekidneyisintimatelyconnectedwiththecirculationsystembymanywaysAnatomyconnectionFunctionalconnectionDiseaseconnectionMedicationconnectionTakingrifampinasanexampleHowthekidneyisconnectedwi

Rifampinis

ahepaticmicrosomalenzymeinducer利福平為肝藥酶誘導(dǎo)劑Followingabsorptionfromthegastrointestinaltract,rifampiniseliminatedrapidlyinthebile,andanenterohepaticcirculationensues.Duringthistime,thedrugisprogressivelydeacetylated,suchthatafter6hours,nearlyalloftheantibioticinthebileisinthedeacetylatedform,whichretainsessentiallyfullantibacterialactivity.Thehalf-lifeofrifampinvariesfrom1.5to5hoursandisincreasedbyhepaticdysfunction.Thehalf-lifeofrifampinisprogressivelyshortenedbyabout40%duringthefirst14daysoftreatment,owingtoinductionofhepaticmicrosomalenzymesthatacceleraterifampindeacetylation.

RifampinisahepaticmicrosoIfthepatientwithchronickidneydiseasewhoseBPisundercontrolonantihypertensivemedication(amloidipine,bisoprolol)reportspoorbloodpressurewhenhebegintotakerifampinforlungtuberculosis,whatwouldyouconsider?Rifampinenhancesthelivermetabolismofantihypertensiveagents,whichleadstoshortenthet1/2ofantihypertensivesandweakentheirBPloweringeffects.Theresultingelevatedpressuremayfurtheracceleraterenaldysfunction.Doesrifampinimpairrenalfunction?-Yes，interstitialnephritisCombinedMedicationCase

Knowhowadrugisconnected

withthekidneyandotherdrugsIfthepatientwithchronicki

Thedrug-relatedrenaldamage

Antimicrobials&

Cyclosporine

抗微生物藥與環(huán)孢素的腎損害Aminoglycosides氨基糖苷類

RenaldamageincludingtubularandglomerulartoxicitySulfonamides磺胺類Crystalformationinthetubule腎小管內(nèi)結(jié)晶損害Rifampin

利福平InterstitialnephritisVancomycin萬(wàn)古霉素InterstitialnephritisCyclosporine環(huán)孢素Nephrotoxicityoccursinthemajorityofpatientstreatedwithcyclosporine.(Hypertensionisalsofrequentlyseen.)Shouldbeavoidedinpatientswithreducedrenalfunction.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Sulfonamides磺胺類腎損害DisturbancesoftheurinarytractbysulfonamidesAlthoughtheriskofcrystalluriawasrelativelyhighwiththeolder,lesssolublesulfonamides,theincidenceofthisproblemisverylowwithmoresolubleagentssuchassulfisoxazole.Crystalluriahasoccurredindehydratedpatientswiththeacquiredimmunedeficiencysyndrome(AIDS)whowerereceivingsulfadiazineforToxoplasmaencephalitis.Fluidintakeshouldbesufficienttoensureadailyurinevolumeofatleast1200ml(inadults).AlkalinizationoftheurinemaybedesirableifurinevolumeorpHisunusuallylowbecausethesolubilityofsulfisoxazoleincreasesgreatlywithslightelevationsofpH.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷類腎損害Approximately8%to26%ofpatientswhoreceiveanaminoglycosideformorethanseveraldayswilldevelopmildrenalimpairmentthatisalmostalwaysreversible.Theelderlyandpatientswithunderlyingrenaldiseasearepronetotheaminoglycosiderenaldamage.Thetoxicityresultsfromaccumulationandretentionofaminoglycosideintheproximaltubularcells.Theinitialmanifestationofdamageatthissiteisexcretionofenzymesoftherenaltubularbrushborder.Afterseveraldays,thereisadefectinrenalconcentratingability,mildproteinuria,andtheappearanceofhyalineandgranularcasts.Theglomerularfiltrationrateisreducedafterseveraladditionaldays.Thenonoliguricphaseofrenalinsufficiencyisthoughttobeduetotheeffectsofaminoglycosidesonthedistalportionofthenephronwithareducedsensitivityofthecollecting-ductepitheliumtoendogenousantidiuretichormone.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷類腎損害Whilesevereacutetubularnecrosismayoccurrarely,themostcommonsignificantfindingisamildriseinplasmacreatinine.Theimpairmentinrenalfunctionisalmostalwaysreversiblebecausetheproximaltubularcellshavethecapacitytoregenerate.

ThemechanismofrenaldamageThebiochemicaleventsleadingtotubularcelldamageandglomerulardysfunctionarepoorlyunderstoodbutmayinvolveperturbationsofthestructureofcellularmembranes.Aminoglycosidesinhibitvariousphospholipases,sphingomyelinases,andATPases,andtheyalterthefunctionofmitochondriaandribosomes.Becauseoftheabilityofcationicaminoglycosidestointeractwithanionicphospholipids,thesedrugsmayimpairthesynthesisofmembrane-derivedautacoidsandintracellularsecondmessengerssuchasprostaglandins,inositolphosphates,anddiacylglycerol.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷類腎損害Derangementsofprostaglandinmetabolismmayexplaintherelationshipbetweentubulardamageandreductioninglomerularfiltrationrate.Othershaveobservedmorphologicalchangesinglomerularendothelialcells(decreasednumberofendothelialfenestrations)andreductionintheglomerularcapillaryultrafiltrationcoefficientinanimalsreceivingaminoglycosides.Ca2+hasbeenshowntoinhibittheuptakeandbindingofaminoglycosidestotherenalbrush-borderluminalmembraneinvitro,andsupplementarydietaryCa2+attenuatesexperimentalnephrotoxicity.Aminoglycosideseventuallyareinternalizedbypinocytosis.Morphologically,thereisclearevidenceofaccumulationofdruginliposomes,ameansbywhichaminoglycosidesaretrapped,concentrated(upto50timestheplasmaconcentration),andpreparedforextrusionintotheurineasmultilamellarphospholipidstructurescalledmyeloidbodies.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

ACEIsandARBsACEIs及ARBs腎損害

ACEIsandARBsPatientswithseverebilateralrenalarterystenosispredictablydeveloprenalfailureonACEIs,becauseglomerularfiltrationisnormallymaintained,inthefaceoflowafferentarteriolarpressure,byangiotensinII,whichselectivelyconstrictsefferentarterioles;hyperkalaemiamaybesevereowingtoreducedaldosteronesecretion.SuchrenalfailureisreversibleprovidedthatitisrecognisedpromptlyandtreatmentwithACEIdiscontinued.ACEIsandARBsarenotrecommendedtousesimultaneouslyinpatientswithrenaldysfunction.腎功能障礙者建議避免使用ACEIs及ARBs

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

AspirinAspirin阿司匹林Saltandwaterretention

Edema,worseningofrenalfunctioninrenal/cardiacpatientsDecreasedeffectivenessofantihypertensivesDecreasedeffectivenessofdiuretics

DecreasedurateexcretionHyperkalemiaUseoflong-termaspirin(asanantipletemedication)shouldbecautiousinpatientswithrenaldisease

Thedrug-relatedrenaldamageProstaglandins

(PGE2andPGI2)

aslocalvasodilators前列腺素是腎臟內(nèi)源性保護(hù)因素Prostaglandins(PGE2andPGI2)：actaslocalvasodilators,areproducedinresponsetosympatheticstimulationandA