Selective acquired long QT syndrome (saLQTS) upon risperidone treatment 英文参考文献.docVIP

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Selective acquired long QT syndrome (saLQTS) upon risperidone treatment 英文参考文献.doc

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Selective acquired long QT syndrome (saLQTS) upon risperidone treatment 英文参考文献

Lazarczyketal.BMCPsychiatry2012,12:220 /1471-244X/12/220 CASE REPORT OpenAccess SelectiveacquiredlongQTsyndrome(saLQTS) uponrisperidonetreatment MaciejJakubLazarczyk1*,ZahirABhuiyan3,NicolasPerrin1andPanteleimonGiannakopoulos1,2 Abstract Background:Numerousstructurallyunrelateddrugs,includingantipsychotics,canprolongQTintervalandtrigger theacquiredlongQTsyndrome(aLQTS).AllofthemarethoughttoactatthelevelofKCNH2,asubunitofthe potassiumchannel.AlthoughtheQT-prolongingdrugsareproscribedinthesubjectswithaLQTS,theindividual responsetodiverseQT-prolongingdrugsmayvarysubstantially. Casepresentation:WereporthereacaseofaLQTSinresponsetosmalldosesofrisperidonethatwasconfirmed atthreeindependentdrugchallengesintheabsenceofotherQT-prolongingdrugs.Ontheotherhand,thepatient didnotrespondwithQTprolongationtosomeotherantipsychotics.Inparticular,theadministrationofclozapine, knowntobeassociatedwithhigherQT-prolongationriskthanrisperidone,hadnoeffectonQT-length.Adetailed geneticanalysisrevealednomutationsorpolymorphismsinKCNH2,KCNE1,KCNE2,SCN5AandKCNQ1genes. Conclusions:OurobservationsuggeststhatsomepatientsmaydisplayaselectiveaLQTStoasingleantipsychotic, withoutapotassiumchannel-relatedgeneticsubstrate.Contrastingwiththeideaofacommontargetofthe aLQTS-triggerringdrugs,ourdatasuggestsexistenceofanalternativetargetprotein,whichunliketheKCNH2 wouldbedrug-selective. Keywords:LongQTsyndrome,AcquiredlongQTsyndrome,SelectiveacquiredlongQTsyndrome,QT, Antipsychotic,Risperidone,Clozapine,KCNH2,hERG Background aLQTS [5-7]. Given the serious health repercussions of The first cases of reversible QT prolongation upon ex- this phenomenon, the aLQTS-triggering drugs are all posure to environmental stressors (mostly drugs) have proscribedinthesevulnerableindividuals,sincetheyare been described in the 1970s and designated as the supposed to have a common mechanism of QT- “acquired long QT syndrome” (aLQTS). The aLQTS- prolongation. triggering drugs are supposed to act at the subunit of However,