药物对肾脏的影响课件

Kidney

and

Drugs

肾脏与药物KidneyandDrugs

肾脏与药物Kidney,Drugs,andMedication

MiscellaneoustalksaboutdrugsandthekidneysUnderstandhowadrugisconnectedwiththekidneyandthewholebodyKidney,Drugs,andMedication

KidneyandMedicationKnowtheactionsiteofdiureticsUnderstandtheroleofthekidneyintheactionandmetabolismofcommonlyuseddrugsUnderstandtheantibioticdistribution,eliminationanddrugchoicesKnowthecommondrug-relatedrenaldamageKnowtheroleofthekidneyinbloodpressurecontrol,pharmacologyofantihypertensivedrugswhichactthroughorrelatedwiththekidneyandclinicaluse

KidneyandMedicationKnowthDiuretics,osmoticdiuretics

Thiazides,Loopdiuretics,K+-sparingdiuretics

mannitol

利尿药与渗透性利尿药:噻嗪类

袢利尿剂保钾利尿剂

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应预先告知患者

Rifampin利福平Upto30%ofado

UnderstandhowadrugisconnectedwiththekidneysandothersystemsaswellasotherdrugsKnowtheurinarysystemFunctionalanatomyConnectionwithothersystemsRoleindrugmetabolismKnowthedrugpharmacologyMetabolismActionApplicationUnwantedeffectKnowthewayofconnectingpharmacologywiththekidneyisimportanttothecareandattendingofapatient

UnderstandhowadrugisconnPyelonephritisandMedication

Acommonandtreatableinfectiousdisease

肾盂肾炎是一种常见的感染性疾病Ascendingurinarytract

infection逆行尿路感染Effectiveantibactericidalmedicationisimportantaswellaseliminationofinfectionsource.消除导致感染的原因大多数肾脏疾病是可治疗和可治愈的PyelonephritisandMedication

Antibiotics抗生素:distribution,eliminationanddrugchoicesAntimicrobialsthatappearinhighconcentrationsinurineoreliminatedmainlythroughthekidneys:Aminoglycosides氨基糖苷类effectiveforurinaryinfectionbutwithunwantedeffects,tendtoresultinrenaldysfunctioninoldpatientsandpatientswithrenaldamagePenicillins,someβ-lactamantibiotics青霉素类与β内酰胺类eliminatedintheurineandarethedrugsofchoicewithsensitivebacteriainfectionQuinolones

喹诺酮类lesssideeffects,effectiveforinfectionofthemostorgansandtissuesespeciallytheurinaryandthelungRifampin

利福平

Antibiotics抗生素:distribution,Howthe

kidneyisconnectedwiththeothersystemsThekidneyisintimatelyconnectedwiththecirculationsystembymanywaysAnatomyconnectionFunctionalconnectionDiseaseconnectionMedicationconnectionTakingrifampinasanexampleHowthekidneyisconnectedwi

Rifampinis

ahepaticmicrosomalenzymeinducer利福平为肝药酶诱导剂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

抗微生物药与环孢素的肾损害Aminoglycosides氨基糖苷类

RenaldamageincludingtubularandglomerulartoxicitySulfonamides磺胺类Crystalformationinthetubule肾小管内结晶损害Rifampin

利福平InterstitialnephritisVancomycin万古霉素InterstitialnephritisCyclosporine环孢素Nephrotoxicityoccursinthemajorityofpatientstreatedwithcyclosporine.(Hypertensionisalsofrequentlyseen.)Shouldbeavoidedinpatientswithreducedrenalfunction.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Sulfonamides磺胺类肾损害DisturbancesoftheurinarytractbysulfonamidesAlthoughtheriskofcrystalluriawasrelativelyhighwiththeolder,lesssolublesulfonamides,theincidenceofthisproblemisverylowwithmoresolubleagentssuchassulfisoxazole.Crystalluriahasoccurredindehydratedpatientswiththeacquiredimmunedeficiencysyndrome(AIDS)whowerereceivingsulfadiazineforToxoplasmaencephalitis.Fluidintakeshouldbesufficienttoensureadailyurinevolumeofatleast1200ml(inadults).AlkalinizationoftheurinemaybedesirableifurinevolumeorpHisunusuallylowbecausethesolubilityofsulfisoxazoleincreasesgreatlywithslightelevationsofpH.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷类肾损害Approximately8%to26%ofpatientswhoreceiveanaminoglycosideformorethanseveraldayswilldevelopmildrenalimpairmentthatisalmostalwaysreversible.Theelderlyandpatientswithunderlyingrenaldiseasearepronetotheaminoglycosiderenaldamage.Thetoxicityresultsfromaccumulationandretentionofaminoglycosideintheproximaltubularcells.Theinitialmanifestationofdamageatthissiteisexcretionofenzymesoftherenaltubularbrushborder.Afterseveraldays,thereisadefectinrenalconcentratingability,mildproteinuria,andtheappearanceofhyalineandgranularcasts.Theglomerularfiltrationrateisreducedafterseveraladditionaldays.Thenonoliguricphaseofrenalinsufficiencyisthoughttobeduetotheeffectsofaminoglycosidesonthedistalportionofthenephronwithareducedsensitivityofthecollecting-ductepitheliumtoendogenousantidiuretichormone.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷类肾损害Whilesevereacutetubularnecrosismayoccurrarely,themostcommonsignificantfindingisamildriseinplasmacreatinine.Theimpairmentinrenalfunctionisalmostalwaysreversiblebecausetheproximaltubularcellshavethecapacitytoregenerate.

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

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷类肾损害Derangementsofprostaglandinmetabolismmayexplaintherelationshipbetweentubulardamageandreductioninglomerularfiltrationrate.Othershaveobservedmorphologicalchangesinglomerularendothelialcells(decreasednumberofendothelialfenestrations)andreductionintheglomerularcapillaryultrafiltrationcoefficientinanimalsreceivingaminoglycosides.Ca2+hasbeenshowntoinhibittheuptakeandbindingofaminoglycosidestotherenalbrush-borderluminalmembraneinvitro,andsupplementarydietaryCa2+attenuatesexperimentalnephrotoxicity.Aminoglycosideseventuallyareinternalizedbypinocytosis.Morphologically,thereisclearevidenceofaccumulationofdruginliposomes,ameansbywhichaminoglycosidesaretrapped,concentrated(upto50timestheplasmaconcentration),andpreparedforextrusionintotheurineasmultilamellarphospholipidstructurescalledmyeloidbodies.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

ACEIsandARBsACEIs及ARBs肾损害

ACEIsandARBsPatientswithseverebilateralrenalarterystenosispredictablydeveloprenalfailureonACEIs,becauseglomerularfiltrationisnormallymaintained,inthefaceoflowafferentarteriolarpressure,byangiotensinII,whichselectivelyconstrictsefferentarterioles;hyperkalaemiamaybesevereowingtoreducedaldosteronesecretion.SuchrenalfailureisreversibleprovidedthatitisrecognisedpromptlyandtreatmentwithACEIdiscontinued.ACEIsandARBsarenotrecommendedtousesimultaneouslyinpatientswithrenaldysfunction.肾功能障碍者建议避免使用ACEIs及ARBs

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

AspirinAspirin阿司匹林Saltandwaterretention

Edema,worseningofrenalfunctioninrenal/cardiacpatientsDecreasedeffectivenessofantihypertensivesDecreasedeffectivenessofdiuretics

DecreasedurateexcretionHyperkalemiaUseoflong-termaspirin(asanantipletemedication)shouldbecautiousinpatientswithrenaldisease

Thedrug-relatedrenaldamageProstaglandins

(PGE2andPGI2)

aslocalvasodilators前列腺素是肾脏内源性保护因素Prostaglandins(PGE2andPGI2)：actaslocalvasodilators,areproducedinresponsetosympatheticstimulationandAngII肾脏局部扩血管的前列腺素系统对交感兴奋及血管紧张素II具有一定的拮抗作用NSAIDsinhibitprostaglandinbiosynthesis.Sinceprostaglandinsareoneofthefactorsthatcounteracttheconstrictionofrenalarterioles,especiallyafferentarterioles,NSAIDsmaybedetrimentaltothekidneybloodflow,leadingtoacuteischemicrenalfailure.非甾体类抗炎药抑制肾脏前列腺素的生成可能减少肾血流导致肾脏缺血Itisespeciallysoinpatientswithheartfailureandliverdisease,glomerularfiltrationdependcriticallyonprostaglandinbiosynthesis.Prostaglandins(PGE2andPGI2)Vasculardisordersofthekidneyandantihypertensives肾血管疾病与抗高血压药ACEIsandARBs-Acase一个临床案例Cardiaccatheterization心导管检查revealednormalcoronaryarteriesinanelderlypatientwithheartfailure,butafterinitiationoftherapywithanACEIandspironolactone,progressivekidneydiseasewithhyperkalemiaandpoorbloodpressurecontrolensued.开始用ACEI及螺内酯后出现进展性肾功能障碍、高血钾，高血压难以控制

RenalDopplerultrasonographysuggestedbilateralrenalarterystenosis,asconfirmedbyangiography.多普勒血流显示双侧肾动脉狭窄，血管造影证实Thepatientunderwentsuccessfulpercutaneous经皮revascularizationinstagesleadingtoareturntonormalleftventricularfunctionandimprovedbloodpressurecontrol.血管成形术后心衰及血压得到改善VasculardisordersofthekidnVasculardisordersofthekidneyandantihypertensives肾血管疾病与抗高血压药ACEIsandARBs-AcaseCardiaccatheterizationrevealednormalcoronaryarteriesinanelderlypatientwithheartfailure,butafterinitiationoftherapywithanACEIandspironolactone,progressivekidneydiseasewithhyperkalemiaandpoorbloodpressurecontrolensued.RenalDopplerultrasonographysuggestedbilateralrenalarterystenosis,asconfirmedbyangiography.Thepatientunderwentsuccessfulpercutaneousrevascularizationinstagesleadingtoareturntonormalleftventricularfunctionandimprovedbloodpressurecontrol.VasculardisordersofthekidnRAASblockadeandglomerular

filtrationRAAS阻断与肾小球滤过EffectsofACEIsandARBsonglomerularfiltrationAngII收缩出球小动脉为主，维持正常GFRSinceAngIIcontractstheefferentarteriolemorethantheafferentarterioles,overdilationofefferentarteriolecanreduceglomerularfiltrationpressureandthusglomerularfiltrationrate.AngII对出球小动脉收缩强于入球小动脉，过度扩张出球小动脉降低肾小球滤过压入出球小动脉出球小动脉AngII收缩出球小动脉为主肾小球毛细血管内平均压60mmHgRAASblockadeandglomerular

Roleofthekidneyincontrollingbloodpressureandthepharmacologyofantihypertensivedrugs见另附幻灯RoleofthekidneyincontrollIodinecontrastagent-inducednephropathy含碘造影剂性肾病请同学们检索一下现代医疗中含碘造影剂使用现状与肾脏损害的情况：含碘造影剂是药物么？含碘造影剂可对肾脏产生什么样的不良反应？如何预防这些造影剂的不良反应？Iodinecontrastagent-induced谢谢！请关注肾脏保护减少损害肾脏的因素请关注肾脏疾病的综合预防与治疗

谢谢！请关注肾脏保护减少损害肾脏的因素Kidney

and

Drugs

肾脏与药物KidneyandDrugs

肾脏与药物Kidney,Drugs,andMedication

MiscellaneoustalksaboutdrugsandthekidneysUnderstandhowadrugisconnectedwiththekidneyandthewholebodyKidney,Drugs,andMedication

KidneyandMedicationKnowtheactionsiteofdiureticsUnderstandtheroleofthekidneyintheactionandmetabolismofcommonlyuseddrugsUnderstandtheantibioticdistribution,eliminationanddrugchoicesKnowthecommondrug-relatedrenaldamageKnowtheroleofthekidneyinbloodpressurecontrol,pharmacologyofantihypertensivedrugswhichactthroughorrelatedwiththekidneyandclinicaluse

KidneyandMedicationKnowthDiuretics,osmoticdiuretics

Thiazides,Loopdiuretics,K+-sparingdiuretics

mannitol

利尿药与渗透性利尿药:噻嗪类

袢利尿剂保钾利尿剂

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应预先告知患者

Rifampin利福平Upto30%ofado

UnderstandhowadrugisconnectedwiththekidneysandothersystemsaswellasotherdrugsKnowtheurinarysystemFunctionalanatomyConnectionwithothersystemsRoleindrugmetabolismKnowthedrugpharmacologyMetabolismActionApplicationUnwantedeffectKnowthewayofconnectingpharmacologywiththekidneyisimportanttothecareandattendingofapatient

UnderstandhowadrugisconnPyelonephritisandMedication

Acommonandtreatableinfectiousdisease

肾盂肾炎是一种常见的感染性疾病Ascendingurinarytract

infection逆行尿路感染Effectiveantibactericidalmedicationisimportantaswellaseliminationofinfectionsource.消除导致感染的原因大多数肾脏疾病是可治疗和可治愈的PyelonephritisandMedication

Antibiotics抗生素:distribution,eliminationanddrugchoicesAntimicrobialsthatappearinhighconcentrationsinurineoreliminatedmainlythroughthekidneys:Aminoglycosides氨基糖苷类effectiveforurinaryinfectionbutwithunwantedeffects,tendtoresultinrenaldysfunctioninoldpatientsandpatientswithrenaldamagePenicillins,someβ-lactamantibiotics青霉素类与β内酰胺类eliminatedintheurineandarethedrugsofchoicewithsensitivebacteriainfectionQuinolones

喹诺酮类lesssideeffects,effectiveforinfectionofthemostorgansandtissuesespeciallytheurinaryandthelungRifampin

利福平

Antibiotics抗生素:distribution,Howthe

kidneyisconnectedwiththeothersystemsThekidneyisintimatelyconnectedwiththecirculationsystembymanywaysAnatomyconnectionFunctionalconnectionDiseaseconnectionMedicationconnectionTakingrifampinasanexampleHowthekidneyisconnectedwi

Rifampinis

ahepaticmicrosomalenzymeinducer利福平为肝药酶诱导剂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

抗微生物药与环孢素的肾损害Aminoglycosides氨基糖苷类

RenaldamageincludingtubularandglomerulartoxicitySulfonamides磺胺类Crystalformationinthetubule肾小管内结晶损害Rifampin

利福平InterstitialnephritisVancomycin万古霉素InterstitialnephritisCyclosporine环孢素Nephrotoxicityoccursinthemajorityofpatientstreatedwithcyclosporine.(Hypertensionisalsofrequentlyseen.)Shouldbeavoidedinpatientswithreducedrenalfunction.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Sulfonamides磺胺类肾损害DisturbancesoftheurinarytractbysulfonamidesAlthoughtheriskofcrystalluriawasrelativelyhighwiththeolder,lesssolublesulfonamides,theincidenceofthisproblemisverylowwithmoresolubleagentssuchassulfisoxazole.Crystalluriahasoccurredindehydratedpatientswiththeacquiredimmunedeficiencysyndrome(AIDS)whowerereceivingsulfadiazineforToxoplasmaencephalitis.Fluidintakeshouldbesufficienttoensureadailyurinevolumeofatleast1200ml(inadults).AlkalinizationoftheurinemaybedesirableifurinevolumeorpHisunusuallylowbecausethesolubilityofsulfisoxazoleincreasesgreatlywithslightelevationsofpH.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷类肾损害Approximately8%to26%ofpatientswhoreceiveanaminoglycosideformorethanseveraldayswilldevelopmildrenalimpairmentthatisalmostalwaysreversible.Theelderlyandpatientswithunderlyingrenaldiseasearepronetotheaminoglycosiderenaldamage.Thetoxicityresultsfromaccumulationandretentionofaminoglycosideintheproximaltubularcells.Theinitialmanifestationofdamageatthissiteisexcretionofenzymesoftherenaltubularbrushborder.Afterseveraldays,thereisadefectinrenalconcentratingability,mildproteinuria,andtheappearanceofhyalineandgranularcasts.Theglomerularfiltrationrateisreducedafterseveraladditionaldays.Thenonoliguricphaseofrenalinsufficiencyisthoughttobeduetotheeffectsofaminoglycosidesonthedistalportionofthenephronwithareducedsensitivityofthecollecting-ductepitheliumtoendogenousantidiuretichormone.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷类肾损害Whilesevereacutetubularnecrosismayoccurrarely,themostcommonsignificantfindingisamildriseinplasmacreatinine.Theimpairmentinrenalfunctionisalmostalwaysreversiblebecausetheproximaltubularcellshavethecapacitytoregenerate.

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

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

Aminoglycosides氨基糖苷类肾损害Derangementsofprostaglandinmetabolismmayexplaintherelationshipbetweentubulardamageandreductioninglomerularfiltrationrate.Othershaveobservedmorphologicalchangesinglomerularendothelialcells(decreasednumberofendothelialfenestrations)andreductionintheglomerularcapillaryultrafiltrationcoefficientinanimalsreceivingaminoglycosides.Ca2+hasbeenshowntoinhibittheuptakeandbindingofaminoglycosidestotherenalbrush-borderluminalmembraneinvitro,andsupplementarydietaryCa2+attenuatesexperimentalnephrotoxicity.Aminoglycosideseventuallyareinternalizedbypinocytosis.Morphologically,thereisclearevidenceofaccumulationofdruginliposomes,ameansbywhichaminoglycosidesaretrapped,concentrated(upto50timestheplasmaconcentration),andpreparedforextrusionintotheurineasmultilamellarphospholipidstructurescalledmyeloidbodies.

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

ACEIsandARBsACEIs及ARBs肾损害

ACEIsandARBsPatientswithseverebilateralrenalarterystenosispredictablydeveloprenalfailureonACEIs,becauseglomerularfiltrationisnormallymaintained,inthefaceoflowafferentarteriolarpressure,byangiotensinII,whichselectivelyconstrictsefferentarterioles;hyperkalaemiamaybesevereowingtoreducedaldosteronesecretion.SuchrenalfailureisreversibleprovidedthatitisrecognisedpromptlyandtreatmentwithACEIdiscontinued.ACEIsandARBsarenotrecommendedtousesimultaneouslyinpatientswithrenaldysfunction.肾功能障碍者建议避免使用ACEIs及ARBs

Thedrug-relatedrenaldamage

Thedrug-relatedrenaldamage

AspirinAspirin阿司匹林Saltandwaterretention

Edema,worseningofrenalfunctioninrenal/cardiacpatientsDecreasedeffectivenessofantihypertensivesDecreasedeffectivenessofdiuretics

DecreasedurateexcretionHyperkalemiaUseoflong-termaspirin(asanantipletemedication)shouldbecautiousinpatientswithrenaldisease

Thedrug-relatedrenaldamageProstaglandins

(PGE2andPGI2)

aslocalvasodilators前列腺素是肾脏内源性保护因素Prostaglandins(PGE2andPGI2)：actaslocalvasodilators,areproducedinresponsetosympatheticstimulationandA