Lorazepam - Wikipedia

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, ... Lorazepam FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Benzodiazepinemedication NottobeconfusedwithLoprazolamorLormetazepam. LorazepamClinicaldataTradenamesAtivan,Tavor,Temesta,others[1]OthernamesO-Chloroxazepam,L-LorazepamAcetateAHFS/Drugs.comMonographMedlinePlusa682053Licensedata US DailyMed: Lorazepam Pregnancycategory AU:C DependenceliabilityHigh[2]RoutesofadministrationBymouth,intramuscular,intravenous,underthetongue,andtransdermalATCcodeN05BA06(WHO)LegalstatusLegalstatus AU:S4(Prescriptiononly) CA:ScheduleIV DE:Prescriptiononly(AnlageIIIforhigherdoses) UK:ControlledDrug(Benz)POM US:ScheduleIV PharmacokineticdataBioavailability85%whentakenbymouthMetabolismLiverglucuronidationOnsetofaction1–5min(IV),15–30min(IM)[3]Eliminationhalf-life10–20hours[4][5][6]Durationofaction12–24hours[3]ExcretionKidneyIdentifiers IUPACname 7-Chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one CASNumber846-49-1 YPubChemCID3958DrugBankDB00186 NChemSpider3821 YUNIIO26FZP769LKEGGD00365 YChEBICHEBI:6539ChEMBLChEMBL580 YCompToxDashboard(EPA)DTXSID7023225ECHAInfoCard100.011.534ChemicalandphysicaldataFormulaC15H10Cl2N2O2Molarmass321.16 g·mol−13Dmodel(JSmol)Interactiveimage SMILES O=C1Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1O InChI InChI=1S/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20) YKey:DIWRORZWFLOCLC-UHFFFAOYSA-N Y  NY (whatisthis?)  (verify) Lorazepam,soldunderthebrandnameAtivanamongothers,isabenzodiazepinemedication.[3]Itisusedtotreatanxietydisorders,troublesleeping,severeagitation,activeseizuresincludingstatusepilepticus,alcoholwithdrawal,andchemotherapy-inducednauseaandvomiting.[3]Itisalsousedduringsurgerytointerferewithmemoryformationandtosedatethosewhoarebeingmechanicallyventilated.[3][7]Itisalsoused,alongwithothertreatments,foracutecoronarysyndromeduetococaineuse.[3]Itcanbegivenbymouthorasaninjectionintoamuscleorvein.[3]Whengivenbyinjectiononsetofeffectsisbetweenoneandthirtyminutesandeffectslastforuptoaday.[3] Commonsideeffectsincludeweakness,sleepiness,lowbloodpressure,andadecreasedefforttobreathe.[3]Whengivenintravenouslythepersonshouldbecloselymonitored.[3]Amongthosewhoaredepressedtheremaybeanincreasedriskofsuicide.[3][8]Withlong-termuse,largerdosesmayberequiredforthesameeffect.[3]Physicaldependenceandpsychologicaldependencemayalsooccur.[3]Ifstoppedsuddenlyafterlong-termuse,benzodiazepinewithdrawalsyndromemayoccur.[3]Olderpeoplemoreoftendevelopadverseeffects.[9]Inthisagegrouplorazepamisassociatedwithfallsandhipfractures.[10]Duetotheseconcerns,lorazepamuseisgenerallyonlyrecommendedforuptotwotofourweeks.[11] Lorazepamwasinitiallypatentedin1963andwentonsaleintheUnitedStatesin1977.[12][13]ItisontheWorldHealthOrganization'sListofEssentialMedicines.[14]Itisavailableasagenericmedication.[3]In2019,itwasthe69thmostcommonlyprescribedmedicationintheUnitedStates,withmorethan10 millionprescriptions.[15][16] Contents 1Medicaluses 1.1Anxiety 1.2Seizures 1.3Sedation 1.4Agitation 1.5Other 2Adverseeffects 2.1Contraindications 2.2Specificgroups 2.3Toleranceanddependence 2.4Withdrawal 2.5Interactions 2.6Overdose 2.7Detectioninbodyfluids 3Pharmacology 3.1Pharmacokinetics 3.2Pharmacodynamics 4Physicalpropertiesandformulations 5History 6Societyandculture 6.1Recreationaluse 6.2Legalstatus 6.3Pricing 7References 8Externallinks Medicaluses[edit] Anxiety[edit] Lorazepamisusedintheshort-termmanagementofsevereanxiety.IntheUS,theFDAadvisesagainstuseofbenzodiazepinessuchaslorazepamforlongerthanfourweeks.[11][17]Itisfastacting,andusefulintreatingfastonsetpanicanxiety.[18] Lorazepamcaneffectivelyreduceagitationandinducesleep,andthedurationofeffectsfromasingledosemakesitanappropriatechoicefortheshort-termtreatmentofinsomnia,especiallyinthepresenceofsevereanxietyornightterrors.Ithasafairlyshortdurationofaction.[19] Withdrawalsymptoms,includingreboundinsomniaandreboundanxiety,mayoccuraftersevendays'useoflorazepam.[20] Seizures[edit] Intravenousdiazepamorlorazepamarefirst-linetreatmentsforconvulsivestatusepilepticus.[21]Lorazepamismoreeffectivethandiazepamandintravenousphenytoininthetreatmentofstatusepilepticusandhasalowerriskofcontinuingseizuresthatmightrequireadditionalmedication.[22]However,phenobarbitalhasasuperiorsuccessratecomparedtolorazepamandotherdrugs,atleastintheelderly.[23][24] Lorazepam'santiconvulsantpropertiesandpharmacokineticprofilemakeintravenoususereliableforterminatingacuteseizures,butinduceprolongedsedation.Oralbenzodiazepines,includinglorazepam,areoccasionallyusedaslong-termprophylactictreatmentofresistantabsenceseizures;becauseofgradualtolerancetotheiranti-seizureeffects,benzodiazepinessuchaslorazepamarenotconsideredfirst-linetherapies.[25] Lorazepam'santiconvulsantandCNSdepressantpropertiesareusefulforthetreatmentandpreventionofalcoholwithdrawalsyndrome.Inthissetting,impairedliverfunctionisnotahazardwithlorazepam,sincelorazepamdoesnotrequireoxidation,intheliverorotherwise,foritsmetabolism.[26][27] Sedation[edit] Lorazepamissometimesusedforindividualsreceivingmechanicalventilation.However,incriticallyillpeople,propofolhasbeenfoundtobesuperiortolorazepambothineffectivenessandoverallcost;asaresult,theuseofpropofolforthisindicationisnowencouraged,whereastheuseoflorazepamisdiscouraged.[28] Itsrelativeeffectivenessinpreventingnewmemoryformation,[29]alongwithitsabilitytoreduceagitationandanxiety,makeslorazepamusefulaspremedication.Itisgivenbeforeageneralanesthetictoreducetheamountofanestheticrequired,orbeforeunpleasantawakeprocedures,suchasindentistryorendoscopies,toreduceanxiety,toincreasecompliance,andtoinduceamnesiafortheprocedure.Lorazepambymouthisgiven90to120minutesbeforeprocedures,andintravenouslorazepamaslateas10minutesbeforeprocedures.[30][31][32]Lorazepamissometimesusedasanalternativetomidazolaminpalliativesedation.[33]Inintensivecareunitslorazepamissometimesusedtoproduceanxiolysis,hypnosis,andamnesia.[34] Agitation[edit] Lorazepamissometimesusedasanalternativetohaloperidolwhenthereistheneedforrapidsedationofviolentoragitatedindividuals,[35][36]buthaloperidolpluspromethazineispreferredduetobettereffectivenessandduetolorazepam'sadverseeffectsonrespiratoryfunction.[37]However,adverseeffectssuchasbehavioraldisinhibitionmaymakebenzodiazepinesinappropriateforsomepeoplewhoareacutelypsychotic.[38]Acutedeliriumissometimestreatedwithlorazepam,butasitcancauseparadoxicaleffects,itispreferablygiventogetherwithhaloperidol.[39]Lorazepamisabsorbedrelativelyslowlyifgivenintramuscularly,acommonrouteinrestraintsituations. Other[edit] Catatoniawithinabilitytospeakisresponsivetolorazepam.Symptomsmayrecurandtreatmentforsomedaysmaybenecessary.Catatoniaduetoabruptoroverlyrapidwithdrawalfrombenzodiazepines,aspartofthebenzodiazepinewithdrawalsyndrome,shouldalsorespondtolorazepamtreatment.[40]Aslorazepamcanhaveparadoxicaleffects,haloperidolissometimesgivenatthesametime.[39][41] Itissometimesusedinchemotherapyinadditiontomedicationsusedtotreatnauseaandvomiting,i.e.nauseaandvomitingcausedorworsenedbypsychologicalsensitizationtothethoughtofbeingsick.[42] Adverseeffects[edit] Manybeneficialeffectsoflorazepam(e.g.,sedative,musclerelaxant,anti-anxiety,andamnesiceffects)maybecomeadverseeffectswhenunwanted.[29]Adverseeffectscanincludesedationandlowbloodpressure;theeffectsoflorazepamareincreasedincombinationwithotherCNSdepressantdrugs.[21][35]Otheradverseeffectsincludeconfusion,ataxia,inhibitingtheformationofnewmemories,pupilconstrictionandhangovereffects.Withlong-termbenzodiazepineuseitisunclearwhethercognitiveimpairmentsfullyreturntonormalafterstoppinglorazepamuse;cognitivedeficitspersistforatleastsixmonthsafterwithdrawal,butlongerthansixmonthsmayberequiredforrecoveryofcognitivefunction.Lorazepamappearstohavemoreprofoundadverseeffectsonmemorythanotherbenzodiazepines;itimpairsbothexplicitandimplicitmemory.[43][44]Intheelderly,fallsmayoccurasaresultofbenzodiazepines.Adverseeffectsaremorecommonintheelderly,andtheyappearatlowerdosesthaninyoungerpeople.Benzodiazepinescancauseorworsendepression.Paradoxicaleffectscanalsooccur,suchasworseningofseizures,orparadoxicalexcitement;paradoxicalexcitementismorelikelytooccurintheelderly,children,thosewithahistoryofalcoholabuse,andinpeoplewithahistoryofaggressionorangerproblems.[9]Lorazepam'seffectsaredose-dependent,meaningthehigherthedose,thestrongertheeffects(andsideeffects)willbe.Usingthesmallestdoseneededtoachievedesiredeffectslessenstheriskofadverseeffects.Sedativedrugsandsleepingpills,includinglorazepam,havebeenassociatedwithanincreasedriskofdeath.[45] Sedationisthesideeffectpeopletakinglorazepammostfrequentlyreport.Inagroupofaround3,500peopletreatedforanxiety,themostcommonsideeffectscomplainedoffromlorazepamweresedation(15.9%),dizziness(6.9%),weakness(4.2%),andunsteadiness(3.4%).Sideeffectssuchassedationandunsteadinessincreasedwithage.[46]Cognitiveimpairment,behaviouraldisinhibitionandrespiratorydepressionaswellashypotensionmayalsooccur.[34][38] Paradoxicaleffects:Insomecases,paradoxicaleffectscanoccurwithbenzodiazepines,suchasincreasedhostility,aggression,angryoutbursts,andpsychomotoragitation.Theseeffectsareseenmorecommonlywithlorazepamthanwithotherbenzodiazepines.[47]Paradoxicaleffectsaremorelikelytooccurwithhigherdoses,inpeoplewithpre-existingpersonalitydisordersandthosewithapsychiatricillness.Frustratingstimulimaytriggersuchreactions,thoughthedrugmayhavebeenprescribedtohelpthepersoncopewithsuchstressandfrustrationinthefirstplace.Asparadoxicaleffectsappeartobedose-related,theyusuallysubsideondosereductionoroncompletewithdrawaloflorazepam.[48][49][50][51][52][53] Suicidality:Benzodiazepinesareassociatedwithincreasedriskofsuicide,possiblyduetodisinhibition.[8]Higherdosagesappeartoconfergreaterrisk. Amnesiceffects:Amongbenzodiazepines,lorazepamhasrelativelystrongamnesiceffects,[29][54]butpeoplesoondeveloptolerancetothiswithregularuse.Toavoidamnesia(orexcesssedation)beingaproblem,theinitialtotaldailylorazepamdoseshouldnotexceed2 mg.Thisalsoappliestousefornightsedation.Fiveparticipantsinasleepstudywereprescribedlorazepam4 mgatnight,andthenextevening,threesubjectsunexpectedlyvolunteeredmemorygapsforpartsofthatday,aneffectthatsubsidedcompletelyaftertwotothreedays'use.[55]Amnesiceffectscannotbeestimatedfromthedegreeofsedationpresent,sincethetwoeffectsareunrelated. High-doseorprolongedparenterallyadministeredlorazepamwithitsassociatedsolventcancausepropyleneglycolintoxicationandpoisoning.[34][56] InSeptember2020,theU.S.FoodandDrugAdministration(FDA)requiredtheboxedwarningbeupdatedforallbenzodiazepinemedicinestodescribetherisksofabuse,misuse,addiction,physicaldependence,andwithdrawalreactionsconsistentlyacrossallthemedicinesintheclass.[57] Contraindications[edit] Thissectionneedsadditionalcitationsforverification.Pleasehelpimprovethisarticlebyaddingcitationstoreliablesources.Unsourcedmaterialmaybechallengedandremoved.Findsources: "Lorazepam" – news ·newspapers ·books ·scholar ·JSTOR(June2017)(Learnhowandwhentoremovethistemplatemessage) Lorazepamshouldbeavoidedinpeoplewith: Allergyorhypersensitivity–Pasthypersensitivityorallergytolorazepam,toanybenzodiazepine,ortoanyoftheingredientsinlorazepamtabletsorinjections Respiratoryfailure–Benzodiazepines,includinglorazepam,maydepresscentralnervoussystemrespiratorydriveandarecontraindicatedinsevererespiratoryfailure.Anexamplewouldbetheinappropriateusetorelieveanxietyassociatedwithacutesevereasthma.Theanxiolyticeffectsmayalsobedetrimentaltoaperson'swillingnessandabilitytofightforbreath.However,ifmechanicalventilationbecomesnecessary,lorazepammaybeusedtofacilitatedeepsedation. Acuteintoxication–Lorazepammayinteractsynergisticallywiththeeffectsofalcohol,narcotics,orotherpsychoactivesubstances.Itshould,therefore,notbeadministeredtoadrunkorintoxicatedperson. Ataxia–Thisisaneurologicalclinicalsign,consistingofunsteadyandclumsymotionofthelimbsandtorso,duetothefailureofgrossmusclemovementcoordination,mostevidentonstandingandwalking.Itistheclassicwayinwhichacutealcoholintoxicationmayaffectaperson.Benzodiazepinesshouldnotbeadministeredtopeoplealready-ataxic. Acutenarrow-angleglaucoma–Lorazepamhaspupil-dilatingeffects,whichmayfurtherinterferewiththedrainageofaqueoushumorfromtheanteriorchamberoftheeye,thusworseningnarrow-angleglaucoma. Sleepapnea–Sleepapneamaybeworsenedbylorazepam'scentralnervoussystemdepressanteffects.Itmayfurtherreducetheperson'sabilitytoprotecthisorherairwayduringsleep.[58] Myastheniagravis–Thisconditionischaracterizedbymuscleweakness,soamusclerelaxantsuchaslorazepammayexacerbatesymptoms. Pregnancyandbreastfeeding–LorazepambelongstotheFoodandDrugAdministration(FDA)pregnancycategoryD,whichmeansitislikelytocauseharmtothedevelopingbabyiftakenduringthefirsttrimesterofpregnancy.Theevidenceisinconclusivewhetherlorazepamiftakenearlyinpregnancyresultsinreducedintelligence,neurodevelopmentalproblems,physicalmalformationsincardiacorfacialstructure,orothermalformationsinsomenewborns.Lorazepamgiventopregnantwomenantenatallymaycausefloppyinfantsyndrome[59]intheneonate,orrespiratorydepressionnecessitatingventilation.Regularlorazepamuseduringlatepregnancy(thethirdtrimester),carriesadefiniteriskofbenzodiazepinewithdrawalsyndromeintheneonate.Neonatalbenzodiazepinewithdrawalmayincludehypotonia,reluctancetosuck,apneicspells,cyanosis,andimpairedmetabolicresponsestocoldstress.Symptomsoffloppyinfantsyndromeandtheneonatalbenzodiazepinewithdrawalsyndromehavebeenreportedtopersistfromhourstomonthsafterbirth.[60]Lorazepammayalsoinhibitfetalliverbilirubinglucuronidation,leadingtoneonataljaundice.Lorazepamispresentinbreastmilk,socautionmustbeexercisedaboutbreastfeeding. Specificgroups[edit] Childrenandtheelderly–Thesafetyandeffectivenessoflorazepamisnotwelldeterminedinchildrenunder18yearsofage,butitisusedtotreatacuteseizures.Doserequirementshavetobeindividualized,especiallyinpeoplewhoareelderlyanddebilitatedinwhomtheriskofoversedationisgreater.Long-termtherapymayleadtocognitivedeficits,especiallyintheelderly,whichmayonlybepartiallyreversible.Theelderlymetabolizebenzodiazepinesmoreslowlythanyoungerpeopleandaremoresensitivetotheadverseeffectsofbenzodiazepinescomparedtoyoungerindividualsevenatsimilarplasmalevels.Additionally,theelderlytendtotakemoredrugswhichmayinteractorenhancetheeffectsofbenzodiazepines.Benzodiazepines,includinglorazepam,havebeenfoundtoincreasetheriskoffallsandfracturesintheelderly.Asaresult,dosagerecommendationsfortheelderlyareabouthalfofthoseusedinyoungerindividualsandusedfornolongerthantwoweeks.[9][61]Lorazepammayalsobeslowertoclearintheelderly,leadingpotentiallytoaccumulationandenhancedeffects.[62]Lorazepam,similartootherbenzodiazepinesandnonbenzodiazepines,causesimpairmentsinbodybalanceandstandingsteadinessinindividualswhowakeupatnightorthenextmorning.Fallsandhipfracturesarefrequentlyreported.Thecombinationwithalcoholincreasestheseimpairments.Partial,butincomplete,tolerancedevelopstotheseimpairments.[10] Liverorkidneyfailure–Lorazepammaybesaferthanmostbenzodiazepinesinpeoplewithimpairedliverfunction.Likeoxazepam,itdoesnotrequireliveroxidation,butonlyliverglucuronidationintolorazepam-glucuronide.Therefore,impairedliverfunctionisunlikelytoresultinlorazepamaccumulationtoanextentcausingadversereactions.[26]Similarlykidneydiseasehasminimaleffectsonlorazepamlevels.[63] Surgicalpremedication–Informedconsentgivenonlyafterreceivinglorazepampremedicationcouldhaveitsvaliditychallengedlater.Staffmustusechaperonestoguardagainstallegationsofabuseduringtreatment.Suchallegationsmayarisebecauseofincompleteamnesia,disinhibition,andimpairedabilitytoprocesscues.Becauseofitsrelativelylongdurationofresidualeffects(sedation,ataxia,hypotension,andamnesia),lorazepampremedicationisbestsuitedforhospitalinpatientuse.Peopleshouldnotbedischargedfromthehospitalwithin24hoursofreceivinglorazepampremedicationunlessaccompaniedbyacaregiver.Theyshouldalsonotdrive,operatemachinery,orusealcoholwithinthisperiod. Drugandalcoholdependence–Theriskofabuseoflorazepamisincreasedindependentpeople.[61] Comorbidpsychiatricdisordersalsoincreasetheriskofdependenceandparadoxicaladverseeffects.[61] Toleranceanddependence[edit] Dependencetypifiedbyawithdrawalsyndromeoccursinaboutone-thirdofindividualswhoaretreatedforlongerthanfourweekswithabenzodiazepine.Higherdosesandlongerperiodsofuseincreasetheriskofdevelopingabenzodiazepinedependence.Potentbenzodiazepineswitharelativelyshorthalflife,suchaslorazepam,alprazolam,andtriazolam,havethehighestriskofcausingadependence.[9]Tolerancetobenzodiazepineeffectsdevelopswithregularuse.Thisisdesirablewithamnesicandsedativeeffectsbutundesirablewithanxiolytic,hypnotic,andanticonvulsanteffects.Peopleinitiallyexperiencedrasticrelieffromanxietyandsleeplessness,butsymptomsgraduallyreturn,relativelysooninthecaseofinsomnia,butmoreslowlyinthecaseofanxietysymptoms.Afterfourtosixmonthsofregularbenzodiazepineuse,evidenceofcontinuedefficacydeclines.[citationneeded] Ifregulartreatmentiscontinuedforlongerthanfourtosixmonths,doseincreasesmaybenecessarytomaintaineffects,buttreatment-resistantsymptomsmayinfactbebenzodiazepinewithdrawalsymptoms.[64]Duetothedevelopmentoftolerancetotheanticonvulsanteffects,benzodiazepinesaregenerallynotrecommendedforlong-termuseforthemanagementofepilepsy.Increasingthedosemayovercometolerance,buttolerancemaythendeveloptothehigherdoseandadverseeffectsmaypersistandworsen.ThemechanismoftolerancetobenzodiazepinesiscomplexandinvolvesGABAAreceptordownregulation,alterationstosubunitconfigurationofGABAAreceptors,uncouplingandinternalisationofthebenzodiazepinebindingsitefromtheGABAAreceptorcomplexaswellaschangesingeneexpression.[9] Thelikelihoodofdependenceisrelativelyhighwithlorazepamcomparedtootherbenzodiazepines.Lorazepam'srelativelyshortserumhalf-life,itsconfinementmainlytoblood,anditsinactivemetabolitecanresultininterdosewithdrawalphenomenaandnext-dosecravings,thatmayreinforcepsychologicaldependence.Becauseofitshighpotency,thesmallestlorazepamtabletstrengthof0.5 mgisalsoasignificantdose.Tominimisetheriskofphysical/psychologicaldependence,lorazepamisbestusedonlyshort-term,atthesmallesteffectivedose.Ifanybenzodiazepinehasbeenusedlong-term,therecommendationisagradualdosetaperoveraperiodofweeks,monthsorlonger,accordingtodoseanddurationofuse,thedegreeofdependenceandtheindividual. Comingofflong-termlorazepamusemaybemorerealisticallyachievedbyagradualswitchtoanequivalentdoseofdiazepamandaperiodofstabilizationonthis,andonlytheninitiatingdosereductions.Theadvantageofswitchingtodiazepamisthatdosereductionsarefeltlessacutely,becauseofthelongerhalf-lives(20–200hours)ofdiazepamanditsactivemetabolites.[65] Withdrawal[edit] Onabruptoroverlyrapiddiscontinuationoflorazepam,anxiety,andsignsofphysicalwithdrawalhavebeenobserved,similartothoseseenonwithdrawalfromalcoholandbarbiturates.Lorazepam,aswithotherbenzodiazepinedrugs,cancausephysicaldependence,addiction,andbenzodiazepinewithdrawalsyndrome.Thehigherthedoseandthelongerthedrugistaken,thegreatertheriskofexperiencingunpleasantwithdrawalsymptoms.Withdrawalsymptomscan,however,occurfromstandarddosagesandalsoaftershort-termuse.Benzodiazepinetreatmentshouldbediscontinuedassoonaspossibleviaaslowandgradualdosereductionregimen.[66]Reboundeffectsoftenresembletheconditionbeingtreated,buttypicallyatamoreintenselevelandmaybedifficulttodiagnose.Withdrawalsymptomscanrangefrommildanxietyandinsomniatomoreseveresymptomssuchasseizuresandpsychosis.Theriskandseverityofwithdrawalareincreasedwithlong-termuse,useofhighdoses,abruptorover-rapidreduction,amongotherfactors.Short-actingbenzodiazepinessuchaslorazepamaremorelikelytocauseamoreseverewithdrawalsyndromecomparedtolonger-actingbenzodiazepines.[9] Withdrawalsymptomscanoccuraftertakingtherapeuticdosesoflorazepamforaslittleasoneweek.Withdrawalsymptomsincludeheadaches,anxiety,tension,depression,insomnia,restlessness,confusion,irritability,sweating,dysphoria,dizziness,derealization,depersonalization,numbness/tinglingofextremities,hypersensitivitytolight,sound,andsmell,perceptualdistortions,nausea,vomiting,diarrhea,appetiteloss,hallucinations,delirium,seizures,tremor,stomachcramps,myalgia,agitation,palpitations,tachycardia,panicattacks,short-termmemoryloss,andhyperthermia.Ittakesabout18–36hoursforthebenzodiazepinetoberemovedfromthebody.[67]Theeaseofphysicaldependencetolorazepam,(Ativanbrandwasparticularlycited),anditswithdrawalwerebroughttotheattentionoftheBritishpublicduringtheearly1980sinEstherRantzen'sBBCTVseriesThat'sLife!,inafeatureonthedrugoveranumberofepisodes. Interactions[edit] Lorazepamisnotusuallyfatalinoverdose,butmaycauserespiratorydepressioniftakeninoverdosewithalcohol.Thecombinationalsocausesgreaterenhancementofthedisinhibitoryandamnesiceffectsofbothdrugs,withpotentiallyembarrassingorcriminalconsequences.Someexpertsadvisethatpeopleshouldbewarnedagainstdrinkingalcoholwhileonlorazepamtreatment,[29][68]butsuchclearwarningsarenotuniversal.[69] Greateradverseeffectsmayalsooccurwhenlorazepamisusedwithotherdrugs,suchasopioidsorotherhypnotics.[63]Lorazepammayalsointeractwithrifabutin.[70]Valproateinhibitsthemetabolismoflorazepam,whereascarbamazepine,lamotrigine,phenobarbital,phenytoin,andrifampinincreaseitsrateofmetabolism.Someantidepressants,antiepilepticdrugssuchasphenobarbital,phenytoinandcarbamazepine,sedativeantihistamines,opiates,antipsychoticsandalcohol,whentakenwithlorazepammayresultinenhancedsedativeeffects.[9] Overdose[edit] Seealso:Benzodiazepineoverdose Incasesofasuspectedlorazepamoverdose,itisimportanttoestablishwhetherthepersonisaregularuseroflorazepamorotherbenzodiazepinessinceregularusecausestolerancetodevelop.Also,onemustascertainwhetherothersubstanceswerealsoingested. Signsofoverdoserangethroughmentalconfusion,dysarthria,paradoxicalreactions,drowsiness,hypotonia,ataxia,hypotension,hypnoticstate,coma,cardiovasculardepression,respiratorydepression,anddeath.However,fataloverdosesonbenzodiazepinesalonearerareandlesscommonthanwithbarbiturates.[71]Suchadifferenceislargelyduetobenzodiazepineactivityasaneuroreceptormodulator,andnotasanactivatorperse.Lorazepamandsimilarmedicationdohoweveractinsynergywithalcohol,whichincreasestheriskofoverdose. Earlymanagementofpeopleunderalertincludesemetics,gastriclavage,andactivatedcharcoal.Otherwise,managementisbyobservation,includingofvitalsigns,supportand,onlyifnecessary,consideringthehazardsofdoingso,givingintravenousflumazenil. Peopleareideallynursedinakind,frustration-freeenvironment,since,whengivenortakeninhighdoses,benzodiazepinesaremorelikelytocauseparadoxicalreactions.Ifshownsympathy,evenquitecrudelyfeigned,peoplemayrespondsolicitously,buttheymayrespondwithdisproportionateaggressiontofrustratingcues.[72]Opportunisticcounselinghaslimitedvaluehere,asthepersonisunlikelytorecallthislater,owingtodrug-inducedanterogradeamnesia. Detectioninbodyfluids[edit] Lorazepammaybequantitatedinbloodorplasmatoconfirmpoisoninginhospitalizedpeople,provideevidenceofanimpaireddrivingarrestortoassistinamedicolegaldeathinvestigation.Bloodorplasmaconcentrationsareusuallyinarangeof10–300μg/linpersonseitherreceivingthedrugtherapeuticallyorinthosearrestedforimpaireddriving.Approximately300–1000μg/lisfoundinpeopleafteracuteoverdosage.[73]Lorazepammaynotbedetectedbycommonlyusedurinedrugscreeningsforbenzodiazepines.[74][75] Pharmacology[edit] Lorazepamhasanxiolytic,sedative,hypnotic,amnesic,anticonvulsant,andmusclerelaxantproperties.[76]Itisahigh-potencyandanintermediate-acting[clarificationneeded]benzodiazepine,anditsuniqueness,[77][78]advantages,anddisadvantagesarelargelyexplainedbyitspharmacokineticproperties(poorwaterandlipidsolubility,highproteinbindingandanoxidativemetabolismtoapharmacologicallyinactiveglucuronideform)andbyitshighrelativepotency(lorazepam1 mgisequalineffecttodiazepam10 mg).[79][80]Thebiologicalhalf-lifeoflorazepamis10–20hours.[81] Pharmacokinetics[edit] Lorazepamishighlyproteinboundandisextensivelymetabolizedintopharmacologicallyinactivemetabolites.[9]Duetoitspoorlipidsolubility,lorazepamisabsorbedrelativelyslowlybymouthandisunsuitableforrectaladministration.However,itspoorlipidsolubilityandhighdegreeofproteinbinding(85–90%[82])meanitsvolumeofdistributionismainlythevascularcompartment,causingrelativelyprolongedpeakeffects.Thiscontrastswiththehighlylipid-solublediazepam,which,althoughrapidlyabsorbedorallyorrectally,soonredistributesfromtheserumtootherpartsofthebody,inparticular,bodyfat.Thisexplainswhyonelorazepamdose,despiteitsshorterserumhalf-life,hasmoreprolongedpeakeffectsthananequivalentdiazepamdose.[83]Lorazepamisrapidlyconjugatedatits3-hydroxygroupintolorazepamglucuronidewhichisthenexcretedintheurine.LorazepamglucuronidehasnodemonstrableCNSactivityinanimals.Theplasmalevelsoflorazepamareproportionaltothedosegiven.Thereisnoevidenceofaccumulationoflorazepamonadministrationuptosixmonths.Onregularadministration,diazepamwillaccumulate,sinceithasalongerhalf-lifeandactivemetabolites,thesemetabolitesalsohavelonghalf-lives. Clinicalexample:Diazepamhaslongbeenadrugofchoiceforstatusepilepticus;itshighlipidsolubilitymeansitgetsabsorbedwithequalspeedwhethergivenorally,orrectally(nonintravenousroutesareconvenientinoutsidehospitalsettings),butdiazepam'shighlipidsolubilityalsomeansitdoesnotremaininthevascularspace,butsoonredistributesintootherbodytissues.So,itmaybenecessarytorepeatdiazepamdosestomaintainpeakanticonvulsanteffects,resultinginexcessbodyaccumulation.Lorazepamisadifferentcase;itslowlipidsolubilitymakesitrelativelyslowlyabsorbedbyanyrouteotherthanintravenously,butonceinjected,itwillnotgetsignificantlyredistributedbeyondthevascularspace.Therefore,lorazepam'santiconvulsanteffectsaremoredurable,thusreducingtheneedforrepeateddoses.Ifapersonisknowntousuallystopconvulsingafteronlyoneortwodiazepamdoses,itmaybepreferablebecausesedativeaftereffectswillbelessthanifasingledoseoflorazepamisgiven(diazepamanticonvulsant/sedativeeffectswearoffafter15–30minutes,butlorazepameffectslast12–24hours).[84]Theprolongedsedationfromlorazepammay,however,beanacceptabletrade-offforitsreliabledurationofeffects,particularlyifthepersonneedstobetransferredtoanotherfacility.Althoughlorazepamisnotnecessarilybetterthandiazepamatinitiallyterminatingseizures,[85]lorazepamis,nevertheless,replacingdiazepamastheintravenousagentofchoiceinstatusepilepticus.[86][87] Lorazepamserumlevelsareproportionaltothedoseadministered.Giving2 mgorallorazepamwillresultinapeaktotalserumlevelofaround20 ng/mlaroundtwohourslater,[82][88]halfofwhichislorazepam,halfitsinactivemetabolite,lorazepam-glucuronide.[89]Asimilarlorazepamdosegivenintravenouslywillresultinanearlierandhigherpeakserumlevel,withahigherrelativeproportionofunmetabolised(active)lorazepam.[90]Onregularadministration,maximumserumlevelsareattainedafterthreedays.Longer-termuse,uptosixmonths,doesnotresultinfurtheraccumulation.[82]Ondiscontinuation,lorazepamserumlevelsbecomenegligibleafterthreedaysandundetectableafteraboutaweek.Lorazepamismetabolizedintheliverbyconjugationintoinactivelorazepam-glucuronide.Thismetabolismdoesnotinvolveliveroxidation,soisrelativelyunaffectedbyreducedliverfunction.Lorazepam-glucuronideismorewater-solublethanitsprecursor,sogetsmorewidelydistributedinthebody,leadingtoalongerhalf-lifethanlorazepam.Lorazepam-glucuronideiseventuallyexcretedbythekidneys,[82]and,becauseofitstissueaccumulation,itremainsdetectable,particularlyintheurine,forsubstantiallylongerthanlorazepam. Pharmacodynamics[edit] Relativetootherbenzodiazepines,lorazepamisthoughttohavehighaffinityforGABAreceptors,[91]whichmayalsoexplainitsmarkedamnesiceffects.[29]ItsmainpharmacologicaleffectsaretheenhancementoftheeffectsoftheneurotransmitterGABAattheGABAAreceptor.[9]Benzodiazepines,suchaslorazepam,enhancetheeffectsofGABAattheGABAAreceptorviaincreasingthefrequencyofopeningofthechlorideionchannelontheGABAAreceptors;whichresultsinthetherapeuticactionsofbenzodiazepines.They,however,donotontheirownactivatetheGABAAreceptors,butrequiretheneurotransmitterGABAtobepresent.Thus,theeffectofbenzodiazepinesistoenhancetheeffectsoftheneurotransmitterGABA.[9][63] Themagnitudeanddurationoflorazepameffectsaredose-related,meaninglargerdoseshavestrongerandlonger-lastingeffects,becausethebrainhassparebenzodiazepinedrugreceptorcapacity,withsingle,clinicaldosesleadingonlytoanoccupancyofsome3%oftheavailablereceptors.[92] Theanticonvulsantpropertiesoflorazepamandotherbenzodiazepinesmaybe,inpartorentirely,duetobindingtovoltage-dependentsodiumchannelsratherthanbenzodiazepinereceptors.Sustainedrepetitivefiringseemstogetlimited,bythebenzodiazepineeffectofslowingrecoveryofsodiumchannelsfrominactivationtodeactivationinmousespinalcordcellcultures,henceprolongingtherefractoryperiod.[93] Physicalpropertiesandformulations[edit] 0.5mgtabletsoftheAtivanbrandoflorazepam Purelorazepamisanalmostwhitepowderthatisnearlyinsolubleinwaterandoil.Inmedicinalform,itismainlyavailableastabletsandasolutionforinjection,but,insomelocations,itisalsoavailableasaskinpatch,anoralsolution,andasublingualtablet. Lorazepamtabletsandsyrupsareadministeredbymouthonly.LorazepamtabletsoftheAtivanbrandalsocontainlactose,microcrystallinecellulose,polacrilin,magnesiumstearate,andcoloringagents(indigocarmineinbluetabletsandtartrazineinyellowtablets).Lorazepamforinjectionformulatedwithpolyethyleneglycol400inpropyleneglycolwith2.0%benzylalcoholaspreservative. Lorazepaminjectablesolutionisadministeredeitherbydeepintramuscularinjectionorbyintravenousinjection.Theinjectablesolutioncomesin1mlampoulescontaining2or4 mgoflorazepam.Thesolventsusedarepolyethyleneglycol400andpropyleneglycol.Asapreservative,theinjectablesolutioncontainsbenzylalcohol.[94]Toxicityfrompropyleneglycolhasbeenreportedinthecaseofapersonreceivingacontinuouslorazepaminfusion.[95]Intravenousinjectionsshouldbegivenslowlyandtheyshouldbecloselymonitoredforsideeffects,suchasrespiratorydepression,hypotension,orlossofairwaycontrol. Peakeffectsroughlycoincidewithpeakserumlevels,[88]whichoccur10minutesafterintravenousinjection,upto60minutesafterintramuscularinjection,and90to120minutesafteroraladministration,[82][88]butinitialeffectswillbenotedbeforethis.Aclinicallyrelevantlorazepamdosewillnormallybeeffectiveforsixto12hours,makingitunsuitableforregularonce-dailyadministration,soitisusuallyprescribedastwotofourdailydoseswhentakenregularly,butthismaybeextendedtofiveorsix,especiallyinthecaseofelderlypeoplewhocouldnothandlelargedosesatonce. Topicalformulationsoflorazepam,whileusedastreatmentfornauseaespeciallyinpeopleinhospice,oughtnotbeusedinthisformandforthispurposeastheyhavenotbeenproveneffective.[96] History[edit] 1987advertisement."Inaworldwherecertaintiesarefew...nowonderAtivanisprescribedbysomanycaringclinicians." Historically,lorazepamisoneofthe"classical"benzodiazepines.Othersincludediazepam,clonazepam,oxazepam,nitrazepam,flurazepam,bromazepam,andclorazepate.[97]LorazepamwasfirstintroducedbyWyethPharmaceuticalsin1977underthebrandnamesAtivanandTemesta.[98]ThedrugwasdevelopedbyD.J.Richards,presidentofresearch.Wyeth'soriginalpatentonlorazepamisexpiredintheUnitedStates. Societyandculture[edit] Recreationaluse[edit] Seealso:Benzodiazepinemisuse Lorazepamisalsousedforotherpurposes,suchasrecreationaluse,whereinthedrugistakentoachieveahigh,orwhenthedrugiscontinuedlong-termagainstmedicaladvice.[99] Alarge-scale,nationwide,U.S.governmentstudyofpharmaceutical-relatedemergencydepartmentvisitsbySAMHSAfoundsedative-hypnoticsarethepharmaceuticalsmostfrequentlyusedoutsideoftheirprescribedmedicalpurposeintheUnitedStates,with35%ofdrug-relatedemergencydepartmentvisitsinvolvingsedative-hypnotics.Inthiscategory,benzodiazepinesaremostcommonlyused.Malesandfemalesusebenzodiazepinesfornonmedicalpurposesequally.Ofdrugsusedinattemptedsuicide,benzodiazepinesarethemostcommonlyusedpharmaceuticaldrugs,with26%ofattemptedsuicidesinvolvingthem.Lorazepamwasthethird-most-commonbenzodiazepineusedoutsideofprescriptionintheseERvisitstatistics.[100] Legalstatus[edit] 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Externallinks[edit] inchem.org–Lorazepamdatasheet benzo.org.uk–AshtonH.Benzodiazepines:HowTheyWorkAndHowtoWithdraw.August2002(The"AshtonManual"). "Lorazepam".DrugInformationPortal.U.S.NationalLibraryofMedicine. vteBenzodiazepines1,4-Benzodiazepines 2-Oxoquazepam 3-Hydroxyphenazepam Bromazepam BMS-906024* Camazepam Carburazepam Chlordiazepoxide Cinazepam Cinolazepam Clonazepam Cloniprazepam Clorazepate Cyprazepam Delorazepam Demoxepam Desmethylflunitrazepam Devazepide* Diazepam Diclazepam Difludiazepam Doxefazepam Elfazepam Ethylcarfluzepate Ethyldirazepate Ethylloflazepate Flubromazepam Fletazepam Fludiazepam Flunitrazepam Flurazepam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Iclazepam Irazepine Kenazepine Ketazolam Lorazepam Lormetazepam Lufuradom* Meclonazepam Medazepam Menitrazepam Metaclazepam Motrazepam N-Desalkylflurazepam Nifoxipam Nimetazepam Nitemazepam Nitrazepam Nitrazepate Nordazepam Nortetrazepam Oxazepam Phenazepam Pinazepam Pivoxazepam Prazepam Proflazepam Quazepam QH-II-66 Reclazepam RO4491533* Ro05-4082 Ro5-4864* Ro07-5220 Ro07-9749 Ro20-8065 Ro20-8552 SH-I-048A Sulazepam Temazepam Tetrazepam Tifluadom* Timelotem* Tolufazepam Triflunordazepam Tuclazepam Uldazepam 1,5-Benzodiazepines Arfendazam Clobazam CP-1414S Lofendazam Triflubazam 2,3-Benzodiazepines* Girisopam GYKI-52466 GYKI-52895 Nerisopam Talampanel Tofisopam Triazolobenzodiazepines Adinazolam Alprazolam Balovaptan* Bromazolam Clonazolam Estazolam Fluadinazolam Flualprazolam Flubromazolam Flunitrazolam Nitrazolam Phenazolam Pyrazolam Rilmazolam(activemetaboliteofRilmazafone) Triazolam Imidazobenzodiazepines Bretazenil Climazolam EVT-201 FG-8205 Flumazenil GL-II-73 Imidazenil 123I-Iomazenil L-655,708 Loprazolam Midazolam PWZ-029 Remimazolam Ro15-4513 Ro48-6791 Ro48-8684 Ro4938581 Sarmazenil SH-053-R-CH3-2′F Oxazolobenzodiazepines Cloxazolam Flutazolam Haloxazolam Mexazolam Oxazolam Thienodiazepines Bentazepam Clotiazepam Ro09-9212 Thienotriazolodiazepines Brotizolam Ciclotizolam Deschloroetizolam Etizolam Flubrotizolam Fluclotizolam Fluetizolam Israpafant* JQ1* Metizolam Thienobenzodiazepines* Olanzapine Telenzepine Pyridodiazepines Lopirazepam Pyridotriazolodiazepines Zapizolam Pyrazolodiazepines Razobazam* Ripazepam Zolazepam Zomebazam Zometapine* Pyrrolodiazepines Premazepam Tetrahydroisoquinobenzodiazepines Clazolam Pyrrolobenzodiazepines* Anthramycin Benzodiazepineprodrugs Alprazolamtriazolobenzophenone Avizafone Rilmazafone *atypicalactivityprofile(notGABAAreceptorligands) vteAnticonvulsants(N03)GABAergicsGABAARPAMs Barbiturates:Barbexaclone Metharbital Methylphenobarbital Pentobarbital Phenobarbital# Primidone;Carbamates:Cenobamate Felbamate;Benzodiazepines:Clobazam Clonazepam Clorazepate Diazepam# Lorazepam# Midazolam Nimetazepam Nitrazepam Temazepam;Others:Bromide(potassiumbromide,sodiumbromide) Imepitoin Paraldehyde Stiripentol GABA-Tinhibitors Fattyacids(andrelated):Valproate Valpromide Valproatepivoxil Vigabatrin Others GABARagonists:Progabide;GAT-1inhibitors:Tiagabine ChannelmodulatorsSodiumblockers Hydantoins:Ethotoin Fosphenytoin Mephenytoin Phenytoin#;Ureides:Acetylpheneturide Chlorphenacemide Phenacemide‡ Pheneturide;Fattyacids:Valproate Valpromide Valproatepivoxil;Carboxamides: Carbamazepine# Eslicarbazepineacetate Oxcarbazepine;Others:Lacosamide Lamotrigine# Rufinamide Topiramate Zonisamide Calciumblockers Oxazolidinediones:Ethadione Paramethadione Trimethadione;Succinimides:Ethosuximide# Mesuximide Phensuximide;Gabapentinoids:Gabapentin Pregabalin;Others:Imepitoin Lamotrigine# Topiramate Zonisamide Potassiumopeners Retigabine OthersCAinhibitors Sulfonamides:Acetazolamide Ethoxzolamide Sultiame Topiramate Zonisamide Others Albutoin Beclamide Brivaracetam Cannabidiol Carisbamate Etiracetam Fenfluramine Ganaxolone Levetiracetam Perampanel #WHO-EM ‡Withdrawnfrommarket Clinicaltrials: †PhaseIII §NevertophaseIII vteAnxiolytics(N05B)5-HT1ARagonists Buspirone Gepirone† Tandospirone GABAARPAMs Benzodiazepines:Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam# Ethylloflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam# Medazepam Nordazepam Oxazepam Pinazepam Prazepam;Others:Alpidem‡ Barbiturates(e.g.,phenobarbital) Carisoprodol Carbamates(e.g.,meprobamate) Chlormezanone‡ Ethanol(alcohol) Etifoxine Imepitoin;Herbs: Kava Skullcap Valerian Gabapentinoids(α2δVDCCblockers) Gabapentin Gabapentinenacarbil Phenibut Pregabalin Antidepressants SSRIs(e.g.,escitalopram) SNRIs(e.g.,duloxetine) SARIs(e.g.,trazodone) TCAs(e.g.,clomipramine#) TeCAs(e.g.,mirtazapine) MAOIs(e.g.,phenelzine);Others:Agomelatine Bupropion Tianeptine Vilazodone Vortioxetine Sympatholytics(Antiadrenergics) Alpha-1blockers(e.g.,prazosin) Alpha-2agonists(e.g.,clonidine,dexmedetomidine,guanfacine) Betablockers(e.g.,propranolol) Others Benzoctamine Cannabidiol Cycloserine Fabomotizole Hydroxyzine Kanna Lavender Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum #WHO-EM ‡Withdrawnfrommarket Clinicaltrials: †PhaseIII §NevertophaseIII vteHypnotics/sedatives(N05C)GABAAAlcohols 2M2B Chloralodol Ethanol(alcohol) Diethylpropanediol Ethchlorvynol Methylpentynol Trichloroethanol Barbiturates Allobarbital Amobarbital Aprobarbital Barbital Butabarbital Butobarbital Cyclobarbital Ethallobarbital Heptabarb Hexobarbital Mephobarbital Methohexital Narcobarbital Pentobarbital Phenallymal Phenobarbital Propylbarbital Proxibarbal Reposal Secobarbital Talbutal Thiamylal Thiopental Thiotetrabarbital Vinbarbital Vinylbital Benzodiazepines Brotizolam Cinolazepam Climazolam Clonazolam Doxefazepam Estazolam Flubromazolam Flunitrazalom Flunitrazepam Flurazepam Flutoprazepam Lorazepam Loprazolam Lormetazepam Midazolam Nimetazepam Nitemazepam Nitrazepam Nitrazolam Quazepam Temazepam Triazolam Carbamates Carisoprodol Emylcamate Ethinamate Hexapropymate Meprobamate Methocarbamol Phenprobamate Procymate Tybamate Imidazoles Etomidate Metomidate Propoxate Monoureides Acecarbromal Apronal(apronalide) Bromisoval Capuride Carbromal Ectylurea Neuroactivesteroids Acebrochol Allopregnanolone Alphadolone Alphaxolone Eltanolone Hydroxydione Minaxolone Progesterone Nonbenzodiazepines Eszopiclone Indiplon Lirequinil Necopidem Pazinaclone Saripidem Suproclone Suriclone Zaleplon Zolpidem Zopiclone Phenols Propofol Piperidinediones Glutethimide Methyprylon Pyrithyldione Piperidione Quinazolinones Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL-164 Others Acetophenone Acetylglycinamidechloralhydrate Bromidecompounds Lithiumbromide Potassiumbromide Sodiumbromide Centalun Chloralbetaine Chloralhydrate Chloralose Clomethiazole Dichloralphenazone Gaboxadol Kavalactones Loreclezole Paraldehyde Petrichloral Sulfonylalkanes Sulfonmethane(sulfonal) Tetronal Trional Triclofos Sesquiterpene Isovaleramide Isovalericacid Valerenicacid GABAB 1,4-Butanediol 4-Fluorophenibut Aceburicacid Baclofen GABOB GHB(sodiumoxybate) GBL GVL Phenibut Tolibut H1Antihistamines Captodiame Cyproheptadine Diphenhydramine Doxylamine Hydroxyzine Methapyrilene Perlapine Pheniramine Promethazine Propiomazine Antidepressants Serotoninantagonistsandreuptakeinhibitors Etoperidone Nefazodone Trazodone Tricyclicantidepressants Amitriptyline Doxepin Trimipramine,etc. Tetracyclicantidepressants Mianserin Mirtazapine,etc. Antipsychotics Typicalantipsychotics Chlorpromazine Thioridazine,etc. Atypicalantipsychotics Olanzapine Quetiapine Risperidone,etc. α2-Adrenergic Clonidine Detomidine Dexmedetomidine Lofexidine Medetomidine Romifidine Tizanidine Xylazine 5-HT2AAntidepressants Trazodone Tricyclicantidepressants Amitriptyline Doxepin Trimipramine,etc. Tetracyclicantidepressants Mianserin Mirtazapine,etc. Antipsychotics Typicalantipsychotics Chlorpromazine Thioridazine,etc. Atypicalantipsychotics Olanzapine Quetiapine Risperidone,etc. Others Niaprazine Melatonin Agomelatine Melatonin Ramelteon Tasimelteon Orexin Daridorexant Lemborexant Suvorexant α2δVDCC Gabapentin Gabapentinenacarbil Mirogabalin Phenibut Pregabalin Others Cannabidiol Cannabis Chlorophenylalkyldiols Fenpentadiol Metaglycodol Phenaglycodol Diethylpropanediol Evoxine Fenadiazole Guaifenesin-relatedmusclerelaxants Chlorphenesin Mephenesin Mephenoxalone Metaxalone Methocarbamol Midaflur Opioids(e.g.,morphine) Passionflower Scopolamine Trazodone UMB68 Valnoctamide vteAntiemetics(A04)5-HT3serotoninionchannelantagonists Alosetron Azasetron Bemesetron Cilansetron Clozapine Dazopride Dolasetron Granisetron Lerisetron Metoclopramide Mianserin Mirtazapine Olanzapine Ondansetron Palonosetron(+netupitant) Quetiapine Ramosetron Ricasetron Tropisetron Zatosetron 5-HTserotoninG-proteinreceptorantagonists Clozapine Cyproheptadine Hydroxyzine Olanzapine Risperidone Ziprasidone CB1agonists(cannabinoids) Dronabinol Nabilone Tetrahydrocannabinol(cannabis) D2/D3antagonists Alizapride Bromopride Chlorpromazine Clebopride Domperidone Haloperidol Hydroxyzine Itopride Metoclopramide Metopimazine Prochlorperazine Thiethylperazine Trimethobenzamide H1antagonists(antihistamines) Cyclizine Dimenhydrinate Diphenhydramine Hydroxyzine Meclizine Promethazine mAChantagonists(anticholinergics) Atropine Diphenhydramine Hydroxyzine(verymild) Hyoscyamine Scopolamine NK1antagonists Aprepitant Fosaprepitant Maropitant Netupitant Rolapitant Others Ceriumoxalate Dexamethasone Lorazepam Midazolam Propofol vteGABAAreceptorpositivemodulatorsAlcohols Brometone Butanol Chloralodol Chlorobutanol(cloretone) Ethanol(alcohol)(alcoholicdrink) Ethchlorvynol Isobutanol Isopropanol Menthol Methanol Methylpentynol Pentanol Petrichloral Propanol tert-Butanol(2M2P) tert-Pentanol(2M2B) Tribromoethanol Trichloroethanol Triclofos Trifluoroethanol Barbiturates (-)-DMBB Allobarbital Alphenal Amobarbital Aprobarbital Barbexaclone Barbital Benzobarbital Benzylbutylbarbiturate Brallobarbital Brophebarbital Butabarbital/Secbutabarbital Butalbital Buthalital Butobarbital Butallylonal Carbubarb Crotylbarbital Cyclobarbital Cyclopentobarbital Difebarbamate Enallylpropymal Ethallobarbital Eterobarb Febarbamate Heptabarb Heptobarbital Hexethal Hexobarbital Metharbital Methitural Methohexital Methylphenobarbital Narcobarbital Nealbarbital Pentobarbital Phenallymal Phenobarbital Phetharbital Primidone Probarbital Propallylonal Propylbarbital Proxibarbital Reposal Secobarbital Sigmodal Spirobarbital Talbutal Tetrabamate Tetrabarbital Thialbarbital Thiamylal Thiobarbital Thiobutabarbital Thiopental Thiotetrabarbital Valofane Vinbarbital Vinylbital Benzodiazepines 2-Oxoquazepam 3-Hydroxyphenazepam Adinazolam Alprazolam Arfendazam Avizafone Bentazepam Bretazenil Bromazepam Brotizolam Camazepam Carburazepam Chlordiazepoxide Ciclotizolam Cinazepam Cinolazepam Clazolam Climazolam Clobazam Clonazepam Clonazolam Cloniprazepam Clorazepate Clotiazepam Cloxazolam CP-1414S Cyprazepam Delorazepam Demoxepam Diazepam Diclazepam Doxefazepam Elfazepam Estazolam Ethylcarfluzepate Ethyldirazepate Ethylloflazepate Etizolam EVT-201 FG-8205 Fletazepam Flubromazepam Flubromazolam Fludiazepam Flunitrazepam Flunitrazolam Flurazepam Flutazolam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Haloxazolam Iclazepam Imidazenil Irazepine Ketazolam Lofendazam Lopirazepam Loprazolam Lorazepam Lormetazepam Meclonazepam Medazepam Menitrazepam Metaclazepam Mexazolam Midazolam Motrazepam N-Desalkylflurazepam Nifoxipam Nimetazepam Nitrazepam Nitrazepate Nitrazolam Nordazepam Nortetrazepam Oxazepam Oxazolam Phenazepam Pinazepam Pivoxazepam Prazepam Premazepam Proflazepam Pyrazolam QH-II-66 Quazepam Reclazepam Remimazolam Rilmazafone Ripazepam Ro48-6791 Ro48-8684 SH-053-R-CH3-2′F Sulazepam Temazepam Tetrazepam Tolufazepam Triazolam Triflubazam Triflunordazepam(Ro5-2904) Tuclazepam Uldazepam Zapizolam Zolazepam Zomebazam Carbamates Carisbamate Carisoprodol Clocental Cyclarbamate Difebarbamate Emylcamate Ethinamate Febarbamate Felbamate Hexapropymate Hydroxyphenamate Lorbamate Mebutamate Meprobamate Nisobamate Pentabamate Phenprobamate Procymate Styramate Tetrabamate Tybamate Flavonoids 6-Methylapigenin Ampelopsin(dihydromyricetin) Apigenin Baicalein Baicalin Catechin EGC EGCG Hispidulin Linarin Luteolin Rc-OMe Skullcapconstituents(e.g.,baicalin) Wogonin Imidazoles Etomidate Metomidate Propoxate Kavaconstituents 10-Methoxyyangonin 11-Methoxyyangonin 11-Hydroxyyangonin Desmethoxyyangonin 11-Methoxy-12-hydroxydehydrokavain 7,8-Dihydroyangonin Kavain 5-Hydroxykavain 5,6-Dihydroyangonin 7,8-Dihydrokavain 5,6,7,8-Tetrahydroyangonin 5,6-Dehydromethysticin Methysticin 7,8-Dihydromethysticin Yangonin Monoureides Acecarbromal Apronal(apronalide) Bromisoval Carbromal Capuride Ectylurea Neuroactivesteroids Acebrochol Allopregnanolone(brexanolone) Alfadolone Alfaxalone 3α-Androstanediol Androstenol Androsterone Certainanabolic-androgenicsteroids Cholesterol DHDOC 3α-DHP 5α-DHP 5β-DHP DHT Etiocholanolone Ganaxolone Hydroxydione Minaxolone ORG-20599 ORG-21465 P1-185 Posovolone Pregnanolone(eltanolone) Progesterone Renanolone SAGE-105 SAGE-324 SAGE-516 SAGE-689 SAGE-872 Testosterone THDOC Zuranolone Nonbenzodiazepines Cyclopyrrolones:Eszopiclone Pagoclone Pazinaclone Suproclone Suriclone Zopiclone Imidazopyridines:Alpidem DS-1 Necopidem Saripidem Zolpidem Pyrazolopyrimidines:Divaplon Fasiplon Indiplon Lorediplon Ocinaplon Panadiplon Taniplon Zaleplon Others:Adipiplon CGS-8216 CGS-9896 CGS-13767 CGS-20625 CL-218,872 CP-615,003 CTP-354 ELB-139 GBLD-345 Imepitoin JM-1232 L-838,417 Lirequinil(Ro41-3696) NS-2664 NS-2710 NS-11394 Pipequaline ROD-188 RWJ-51204 SB-205,384 SX-3228 TGSC01AA TP-003 TPA-023 TP-13 U-89843A U-90042 Viqualine Y-23684 Phenols Fospropofol Propofol Thymol Piperidinediones Glutethimide Methyprylon Piperidione Pyrithyldione Pyrazolopyridines Cartazolate Etazolate ICI-190,622 Tracazolate Quinazolinones Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL-164 Volatiles/gases Acetone Acetophenone Acetylglycinamidechloralhydrate Aliflurane Benzene Butane Butylene Centalun Chloral Chloralbetaine Chloralhydrate Chloroform Cryofluorane Desflurane Dichloralphenazone Dichloromethane Diethylether Enflurane Ethylchloride Ethylene Fluroxene Gasoline Halopropane Halothane Isoflurane Kerosine Methoxyflurane Methoxypropane Nitricoxide Nitrogen Nitrousoxide Norflurane Paraldehyde Propane Propylene Roflurane Sevoflurane Synthane Teflurane Toluene Trichloroethane(methylchloroform) Trichloroethylene Vinylether Others/unsorted 3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins(e.g.,ivermectin) Bromidecompounds(e.g.,lithiumbromide,potassiumbromide,sodiumbromide) Carbamazepine Chloralose Chlormezanone Clomethiazole DEABL Dihydroergolines(e.g.,dihydroergocryptine,dihydroergosine,dihydroergotamine,ergoloid(dihydroergotoxine)) DS2 Efavirenz Etazepine Etifoxine Fenamates(e.g.,flufenamicacid,mefenamicacid,niflumicacid,tolfenamicacid) Fluoxetine Flupirtine Hopantenicacid Lanthanum Lavenderoil Lignans(e.g.,4-O-methylhonokiol,honokiol,magnolol,obovatol) Loreclezole Menthylisovalerate(validolum) Monastrol Niacin Niacinamide Org25,435 Phenytoin Propanidid Retigabine(ezogabine) Safranal Seproxetine Stiripentol Sulfonylalkanes(e.g.,sulfonmethane(sulfonal),tetronal,trional) Terpenoids(e.g.,borneol) Topiramate Valerianconstituents(e.g.,isovalericacid,isovaleramide,valerenicacid,valerenol) Unsortedbenzodiazepinesitepositivemodulators:α-Pinene MRK-409(MK-0343) TCS-1105 TCS-1205 Seealso:Receptor/signalingmodulators•GABAreceptormodulators•GABAmetabolism/transportmodulators vteIonchannelmodulatorsCalciumVDCCsBlockers L-type-selective:Dihydropyridines:Amlodipine Aranidipine Azelnidipine Barnidipine Clevidipine Cronidipine Darodipine Dexniguldipine Elgodipine Elnadipine Felodipine Flordipine Furnidipine Iganidipine Isradipine Lacidipine Lemildipine Lercanidipine Levamlodipine Levniguldipine Manidipine Mepirodipine Mesudipine Nicardipine Nifedipine Niguldipine Niludipine Nilvadipine Nimodipine Nisoldipine Nitrendipine Olradipine Oxodipine Palonidipine Pranidipine Ryodipine(riodipine) Sagandipine Sornidipine Teludipine Tiamdipine Trombodipine Vatanidipine;Diltiazemderivatives:Clentiazem Diltiazem Iprotiazem Nictiazem Siratiazem;Phenylalkylamines:Anipamil Dagapamil Devapamil Dexverapamil Emopamil Etripamil Falipamil Gallopamil Levemopamil Nexopamil Norverapamil Ronipamil Tiapamil Verapamil;Others:AH-1058 Brinazarone Budiodarone Celivarone Cyproheptadine Dronedarone Fantofarone SR-33805 Tetrahydropalmatine N-type-selective:ω-Conotoxins ω-ConotoxinGVIA Caroverine HuwentoxinXVI Leconotide(ω-conotoxinCVID) PD-173212 Ralfinamide Safinamide Z160 Ziconotide(ω-conotoxinMVIIA) P-type-selective:ω-AgatoxinIVA ω-AgatoxinIVB R-type-selective:SNX-482 T-type-selective:ABT-639 ML-218 Niflumicacid NNC55-0396 ProTxI Z944 Zonisamide Non-selective:ω-AgatoxinTK ω-ConotoxinMVIIC Benidipine Bepridil Cilnidipine Cinnarizine Dotarizine Efonidipine Flunarizine Lamotrigine Levetiracetam Lomerizine Loperamide Mibefradil NP078585 Rutheniumred TROX-1 α2δsubunit-selective(gabapentinoids):4-Methylpregabalin Arbaclofen Arbaclofenplacarbil Atagabalin Baclofen Gabapentin Gabapentinenacarbil Imagabalin Mirogabalin PD-200,347 PD-217,014 PD-299,685 Phenibut Pregabalin Others/unsorted:Bencyclane Berbamine Bevantolol Canadine Carboxyamidotriazole Cycleanine Dauricine Dimeditiapramine Diproteverine Enpiperate Eperisone Elpetrigine Ethadione Ethanol(alcohol) Ethosuximide Fasudil Fendiline Fostedil Imepitoin JTV-519 Lidoflazine Magnesium Manoalide Mesuximide Monatepil Naftopidil OchratoxinA Osthol Otiloniumbromide Paramethadione Phensuximide Pinaveriumbromide Prenylamine Rhynchophylline Sesamodil Silperisone Sipatrigine Terodiline Tetrandrine Tolperisone Trimethadione Valperinol Activators L-type-selective:BayK8644 PotassiumVGKCsBlockers 3,4-Diaminopyridine(amifampridine) 4-Aminopyridine(fampridine/dalfampridine) Adekalant Almokalant Amiodarone Azimilide Bretylium Bunaftine Charybdotoxin Clamikalant Conotoxins Dalazatide Dendrotoxin Dofetilide Dronedarone E-4031 Hanatoxin HgeTx1 HsTx1 Ibutilide Inakalant Kaliotoxin Linopirdine LolitremB Maurotoxin Nifekalant Notoxin Paxilline Pinokalant Quinidine ShK-186 Sotalol Tedisamil Terikalant Tetraethylammonium Vernakalant hERG(KCNH2,Kv11.1)-specific:Ajmaline Amiodarone AmmTX3 Astemizole Azaspiracid AZD1305 Azimilide Bedaquiline BeKm-1 BmTx3 BRL-32872 Chlorpromazine Cisapride Clarithromycin Darifenacin Dextropropoxyphene Diallyltrisulfide Domperidone E-4031 Ergtoxins Erythromycin Gigactonine Haloperidol Ketoconazole Norpropoxyphene Orphenadrine Pimozide PNU-282,987 Promethazine Quinidine Ranolazine Roxithromycin Sertindole Solifenacin Tamulotoxin Terodiline Terfenadine Thioridazine Tolterodine Vanoxerine Vernakalant KCNQ(Kv7)-specific:Linopirdine XE-991 Spookytoxin(SsTx) Activators KCNQ(Kv7)-specific:Flupirtine Retigabine IRKsBlockers KATP-specific:Acetohexamide Carbutamide Chlorpropamide Glibenclamide(glyburide) Glibornuride Glicaramide Gliclazide Glimepiride Glipizide Gliquidone Glisoxepide Glyclopyramide Glycyclamide Metahexamide Mitiglinide Nateglinide Repaglinide Tolazamide Tolbutamide GIRK-specific:Barium Caramiphen Cloperastine Clozapine Dextromethorphan Ethosuximide Ifenprodil Tertiapin Tipepidine Activators KATP-specific:Aprikalim Bimakalim Cromakalim Diazoxide Emakalim Levcromakalim Mazokalim Minoxidil Minoxidilsulfate Naminidil Nicorandil Pinacidil Rilmakalim Sarakalim GIRK-specific:ML-297(VU0456810) KCaBlockers BKCa-specific:Ethanol(alcohol) GAL-021 Activators BKCa-specific:Flufenamicacid Meclofenamicacid Niflumicacid Nimesulide Rottlerin(mallotoxin) Tolfenamicacid K2PsBlockers 12-O-Tetradecanoylphorbol-13-acetate Arachidonicacid Fluoxetine Norfluoxetine Activators Riluzole SodiumVGSCsBlockers Antianginals:Ranolazine Antiarrhythmics(classI):Ajmaline Aprindine Disopyramide Dronedarone Encainide Flecainide Lidocaine Lorajmine Lorcainide Mexiletine Moricizine Pilsicainide Prajmaline Procainamide Propafenone Quinidine Sparteine Tocainide Anticonvulsants:Acetylpheneturide Carbamazepine Cenobamate Chlorphenacemide Elpetrigine Eslicarbazepineacetate Ethotoin Fosphenytoin Lacosamide Licarbazepine Mephenytoin Oxcarbazepine Oxitriptyline Phenacemide Pheneturide Phenytoin Rufinamide Sipatrigine Topiramate Sodiumvalproate Valnoctamide Valproatepivoxil Valproatesemisodium Valproicacid Valpromide Zonisamide Localanesthetics:pFBT Amylocaine Articaine Benzocaine Bupivacaine(Levobupivacaine,Ropivacaine) Butacaine Butamben Chloroprocaine Cinchocaine Cocaine Cyclomethycaine Dimethocaine Diphenhydramine Etidocaine Hexylcaine Iontocaine Lidocaine Mepivacaine Meprylcaine Metabutoxycaine Orthocaine Piperocaine Prilocaine Procaine Propoxycaine Proxymetacaine Risocaine Tetracaine Trimecaine Analgesics:AZD-3161 DSP-2230 Funapide GDC-0276 NKTR-171 PF-04531083 PF-05089771 Ralfinamide Raxatrigine RG7893(GDC-0287) Toxins:Conotoxins Neosaxitoxin Saxitoxin Tetrodotoxin ZetekitoxinAB Others:Buprenorphine Evenamide Menthol(mint) Safinamide Tricyclicantidepressants Activators Aconitine Atracotoxins(ω-Atracotoxin,Robustoxin,Versutoxin) Batrachotoxin Ciguatoxins Grayanotoxins Poneratoxin ENaCBlockers Amiloride Benzamil Triamterene Activators Solnatide ASICsBlockers A-317567 Amiloride Aspirin Ibuprofen PcTX1 ChlorideCaCCsBlockers Crofelemer DIDS Ethacrynicacid Flufenamicacid Fluoxetine Furosemide Glibenclamide Mefloquine Mibefradil Niflumicacid Activators Carbachol CFTRBlockers Glibenclamide Lonidamine Piretanide Activators 1,7-Phenanthroline 1,10-Phenanthroline 4,7-Phenanthroline 7,8-Benzoquinoline Ivacaftor Phenanthridine UnsortedBlockers Bumetanide Flufenamicacid Meclofenamicacid Mefenamicacid Mepacrine Niflumicacid Talniflumate Tolfenamicacid Trifluoperazine OthersTRPs Seehereinstead. LGICs Seehereinstead. Seealso:Receptor/signalingmodulators•Transientreceptorpotentialchannelmodulators Portal: Medicine Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Lorazepam&oldid=1094885481" Categories:AntiemeticsAnxiolyticsBenzodiazepinesWyethbrandsPfizerbrandsChemicalsubstancesforemergencymedicineChloroarenesGABAAreceptorpositiveallostericmodulatorsLactamsSodiumchannelblockersWorldHealthOrganizationessentialmedicinesLactimsHiddencategories:CS1Dutch-languagesources(nl)CS1French-languagesources(fr)SourceattributionWebarchivetemplatewaybacklinksArticleswithshortdescriptionShortdescriptionmatchesWikidataUsedmydatesfromOctober2021ArticleswithchangedDrugBankidentifierECHAInfoCardIDfromWikidataDrugboxeswhichcontainchangestoverifiedfieldsDrugboxeswhichcontainchangestowatchedfieldsArticlesneedingadditionalreferencesfromJune2017AllarticlesneedingadditionalreferencesAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromApril2019WikipediaarticlesneedingclarificationfromJanuary2020Wikipediamedicinearticlesreadytotranslate Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Inotherprojects WikimediaCommons Languages AfrikaansالعربيةتۆرکجهCatalàČeštinaCymraegDeutschΕλληνικάEspañolEuskaraفارسیFrançaisGalego한국어ՀայերենHrvatskiBahasaIndonesiaItalianoעבריתLatinaമലയാളംMinangkabauNederlands日本語Norskbokmålଓଡ଼ିଆPolskiPortuguêsRomânăРусскийSimpleEnglishSlovenščinaСрпски/srpskiSrpskohrvatski/српскохрватскиSundaSuomiSvenskaไทยTürkçeУкраїнська吴语中文 Editlinks