藥物對腎臟的影響課件

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應預先告知患者

Rifampin利福平Upto30%ofado

UnderstandhowadrugisconnectedwiththekidneysandothersystemsaswellasotherdrugsKnowtheurinarysystemFunctionalanatomyConnectionwithothersystemsRoleindrugmetabolismKnowthedrugpharmacologyMetabolismActionApplicationUnwantedeffectKnowthewayofconnectingpharmacologywiththekidneyisimportanttothecareandattendingofapatient

UnderstandhowadrugisconnPyelonephritisandMedication

Acommonandtreatableinfectiousdisease

腎盂腎炎是一種常見的感染性疾病Ascendingurinarytract

infection逆行尿路感染Effectiveantibactericidalmedicationisimportantaswellaseliminationofinfectionsource.消除導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腎小管內結晶損害Rifampin

利福平InterstitialnephritisVancomycin萬古霉素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前列腺素是腎臟內源性保護因素Prostaglandins(PGE2andPGI2)：actaslocalvasodilators,areproducedinresponsetosympatheticstimulationandAngII腎臟局部擴血管的前列腺素系統(tǒng)對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一個臨床案例Cardiaccatheterization心導管檢查revealednormalcoronaryarteriesinanelderlypatientwithheartfailure,butafterinitiationoftherapywithanACEIandspironolactone,progressivekidneydiseasewithhyperkalemiaandpoorbloodpressurecontrolensued.開始用ACEI及螺內酯后出現(xiàn)進展性腎功能障礙、高血鉀，高血壓難以控制

RenalDopplerultrasonographysuggestedbilateralrenalarterystenosis,asconfirmedbyangiography.多普勒血流顯示雙側腎動脈狹窄，血管造影證實Thepatientunderwentsuccessfulpercutaneous經(jīng)皮revascularizationinstagesleadingtoareturntonormalleftventricularfunctionandimprovedbloodpressurecontrol.血管成形術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阻斷與腎小球濾過EffectsofACEIsandARBsonglomerularfiltrationAngII收縮出球小動脈為主，維持正常GFRSinceAngIIcontractstheefferentarteriolemorethantheafferentarterioles,overdilationofefferentarteriolecanreduceglomerularfiltrationpressureandthusglomerularfiltrationrate.AngII對出球小動脈收縮強于入球小動脈，過度擴張出球小動脈降低腎小球濾過壓入出球小動脈出球小動脈AngII收縮出球小動脈為主腎小球毛細血管內平均壓60mmHgRAASblockadeandglomerular

Roleofthekidneyincontrollingbloodpressureandthepharmacologyofantihypertensivedrugs見另附幻燈RoleofthekidneyincontrollIodinecontrastagent-inducednephropathy含碘造影劑性腎病請同學們檢索一下現(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？含碘造影劑可對腎臟產生什么樣的不良反應？如何預防這些造影劑的不良反應？Iodinecontrastagent-induced謝謝！請關注腎臟保護減少損害腎臟的因素請關注腎臟疾病的綜合預防與治療

謝謝！請關注腎臟保護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應預先告知患者

Rifampin利福平Upto30%ofado

UnderstandhowadrugisconnectedwiththekidneysandothersystemsaswellasotherdrugsKnowtheurinarysystemFunctionalanatomyConnectionwithothersystemsRoleindrugmetabolismKnowthedrugpharmacologyMetabolismActionApplicationUnwantedeffectKnowthewayofconnectingpharmacologywiththekidneyisimportanttothecareandattendingofapatient

UnderstandhowadrugisconnPyelonephritisandMedication

Acommonandtreatableinfectiousdisease

腎盂腎炎是一種常見的感染性疾病Ascendingurinarytract

infection逆行尿路感染Effectiveantibactericidalmedicationisimportantaswellaseliminationofinfectionsource.消除導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腎小管內結晶損害Rifampin

利福平InterstitialnephritisVancomycin萬古霉素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前列腺素是腎臟內源性保護因素Prostaglandins(PGE2andPGI2)：actaslocalvasodilators,areproducedinresponsetosympatheticstimulationandA