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by Josh Wiley, PharmD Candidate

Introduction Ecstasy(3,4-methylene-dioxymethamphetamine,MDMA)hasthreepropertiesthatmakeitunlikeanyotherrecreationaldrugofabuse.Itcontainsstimulatorypropertiesofamphetamines,hallucinogenicpropertiesofmescaline,andlimitedanxiolyticproperties.MDMAhasbecomeknownasthe“lovedrug”andalsogoesbyotherstreetnames,whichinclude:“XTC,”“Adam,”“M&M,”or“E.”Itispopularat“raves”andistakenforitsmood-enhancingproperties.Accordingtothe2003NationalSurveyofDrugUseandHealth(NSDUH),2.1millionAmericansaged12andolderhavetriedMDMA.Theriskofdeathforfirst-timeusershasbeenestimatedtobebetween1in2000to1in5000.1MDMAtabletscancontainmultipleadulterants,includingdextromethorphan,amphetamine,methamphetamine,ketamine,caffeine,andacetaminophen.1

Pharmacology/ Kinetics

MDMAcausesthereleaseofseveralneurotransmitters,primarilyserotonin(5HT),butalsodopamine(DA),andnorepinephrine(NE).Itinhibitsthereuptakeofserotoninandhasthepotential,withchronicuse,todestroyserotoninnerveterminals.Theseneurotransmittersareinvolvedinmoodregulation,thermoregulation,sleepcontrol,appetite,reward,andtheautonomicnervoussystem. MDMAisusuallyformulatedasatabletfor

ingestion,althoughitcanbesnorted,smoked,orinjected.Serumhalf-livesgenerallyrangefrom7to10hoursinacidurineto16to31hoursinalkalineurine.2Thetypicalhalf-lifeis8hoursandatypical“high”lasts3to5hours.

Adverse Effects Adverseeffectsincludejawclenching,lossofappetite,trismus,bruxism,nausea,drymouth,confusion,sweating,headache,fatigue,insomnia,constantrestlessmovementsofthelegsandmuscleaches.Majoradverseeffectsincludehypertension,tachycardia, (cont. on pg. 2)

Official Newsletter of the Utah Poison Control Center

I n t h I s I s s U E

Ecstasy

tramadol

Mushrooms

Outreach Education

Meet the UPCC staff: Dr. Martin Caravati

TOXICOLOGYTODAY A program of the University of Utah College of Pharmacy

t O D A Y The University of UtahThe University of UtahUtah Poison Control Center

2007 • VOlUME 9 • IssUE 4

ECsTAsY

Source:NationalInstituteofDrugAbuse

TrAmADOLby Tung Vu, PharmD Candidate

Tramadolisacentrally-actinganalgesicavailableintheUSfororaladministrationasanimmediateandextended-releasetabletandincombinationwithacetaminophen.Itisacodeineanalogthathasweakaffinityformu-opioidreceptorsandalsoinhibitsreuptakeforserotonin(5-HT)andnorepinephrine(NE).Themostcommonadverseeffectsassociatedwithtramadolincludedizziness,drowsiness,headache,vertigo,constipation,andnausea.ItismetabolizedintheliverbyCYP2D6and3A4andincreasedadverseeffectsmaybeseenwithpatientsonothermedicationsthatinhibittheactivityoftheseenzymes.Becausetramadolinhibitsthe

uptakeofserotonin,serotoninsyndromeisapossibilityespeciallyincombinationwithotherserotonergicmedications. Toxicityassociatedwithtramadolisadirectextensionofitspharmacologicaction.Intwomulti-centerstudiesoftramadolexposuresreportedtopoisoncontrolcenters,themostcommonclinicaleffectsreportedwereCNSdepression,nauseaandvomiting,tachycardiaandseizures.1,2Respiratorydepressionoccurredrarely.Inonecaseseriesinvolving87reports,seizuresoccurredin7(8%)casesand6/7patientsexperiencedasingleseizurethatwasbriefandself-limiting.2Theotherpatienthadtwowitnessedseizures.Inasecondseries26of190tramadolexposuresreportedtoastate-widepoisoncenternetworkseized,80%hadasingleseizure,(cont. on pg. 3)

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(cont. from pg. 1) Ecstasy

QTprolongation,psychosis,panicattacks,malignanthyperthermia,seizures,cerebralhemorrhage,hepatitis,rhabdomyolysis,disseminatedintravascularcoagulation,andacuterenalfailure.3 Hypertensionandtachycardiaareduetoexcesssympathomimeticeffects,primarilyfromnorepinephrine.Inavolunteerhumanstudy,MDMAincreasedsystolicbloodpressure40mmHgandtheheartrateby30beatsperminute.3

Clinical toxicology/ toxicokinetics MDMAisadrugcommonlyassociatedwiththeclubscene.EnvironmentalfactorsthatmayconfoundormagnifytoxicityofMDMAincludeambienttemperatureandphysicalexertion.Dancinginpoorlyventilatedareascanleadtoincreaedbodytemperature,excessivefluidlossandincreasedmuscleactivity. Recreationaldosesareusually50-100mgorally(1.5mg/kg).2MDMAcanleadtoconfusion,delirium,hyponatremia,hyperthermia,cardiovascularcomplications,seizures,rhabdomyolysis,hepatotoxicityandmultisystemorganfailure.Hepatotoxicitymaybeanisolatedfindingorassociatedwithhyperpyrexia.Itcanoccureitherafteranacutesingleoverdoseorwithchronicuse.Dilutionalhyponatremiacanresultfromwaterintoxicationduetodrinking

largevolumesofwaterorcarbonatedbeveragesinordertopreventdehydration.Clubshavebeenencouragedtoprovide“chillout”areaswithdrinkingwateravailable.1MDMAcanalsocauseSIADH,whichcanresultinhyponatremia.Serumsodiumconcentrationsaslowas115mEq/Lhavebeenreported.2Womenappeartobeatfour-foldincreasedriskofhyponatremiaandcoma.4 Thedurationandmagnitudeofhyperthermiaarepredictorsofmortalityrisk.Mortalityishighwhenthepeakcoretemperatureexceeds42°C.1Hyperthermiacanalsocausecomplicationssuchasrhabdomyolysis,impairedconsciousness,seizures,disseminatedintravascularcoagulation,andmulti-organsystemfailure.Individualswithpreexistinghypertensionorothercardiaccomplicationsareatincreasedriskofsuddendeath.1

treatment ObserveacutelyintoxicatedpatientintheEDforatleast4hours.Considerobtainingserumelectrolytes,creatinine,liverfunction,creatinekinaseandanelectrocardiograminsymptomaticpatients.Supportivecarewithsimplecoolingmethodsisthemainstayoftherapyforhyperthermia.Hyperthermiaassociatedwithseveremusclerigiditycanbetreatedwiththeskeletalmusclerelaxantdantrolene.1 Hypertension,tachycardia,seizuresandagitationshouldbeinitiallytreatedwithbenzodiazepines.Ifseverehypertensionandtachycardiapersists,the

combinationofabetablockerandavasodilator,suchasnitroglycerinornitroprusside,shouldbeused.Theuseofbetablockersalonecanresultinworseninghypertensionduetounopposedalphaadrenergiceffectsandvasoconstriction. Hyponatremiaisgenerallymanagedwithfluidrestriction.Inseverecases,hypertonicsalinecanbeused.Cautionisrequiredwhencorrectinghyponatremia;iftheserumsodiumiscorrectedtoorapidly,osmoticdemyelinationsyndromecanoccur.

TOXICOLOGYTODAY A publication for Health Professionals.

sEnIOrmEDICATIOnsAfETYPrOGrAm

O U t r E A C h E D U C A t I O n

MartyMalheiro,theUtahPoisonControlCenter(UPCC)outreacheducatorwaspartofateamthatdevelopedanationalpoisonpreventioneducationprogramaimedatolderadults.Theprogram,basedontheHealthBeliefModeltheory,addressedpoisonpreventionandmedicationmisuse.Pilottestedwith100olderadults,theevaluationshowedtheprogramwassuccessfulinraisingawarenessandchangingbehaviorregardingthepotentialadverseconsequencesassociatedwithmedicationmisuseanddruginteractions.Twoofthemostpositivefindingsincluded:

asignificantincreaseinknowledgewiththequestion,“Youneedtotellyourdoctoraboutvitaminsyouaretaking.”asignificantchangeinattituderelatedtothequestion,“Youcontrolyourmedicinesandhowtheyshouldbecombined.”

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2.

Onemonthafterthetraining,99%ofparticipantsrememberedtheprogramand20%hadmodifiedtheirmedicinetakinghabits.Foradditionalinformationaboutthestudy,contactMartyMalheiroat801/587-0603.

Checkoutourwebsiteformorepoisonpreventioninformationat

www.utahpoisoncontrol.org

referencesHallAP,HenryJA.Acutetoxiceffectsof“Ecstasy”(MDMA)andrelatedcompounds:overviewofpathophysiologyandclinicalmanage-ment.BJA2006;96(6):678-685.

ShannonM.Methylenedioxy-methamphetamine(MDMA,“Ectsasy).PedEmergCare2000;16(5):377-380.

MasM,etal.CardiovascularandNeuroendocrineEffectsandPharmacokineticsof3,4-MethylenedioxymethamphetamineinHumans.JPharmacolandExpTher1999;290(1):136-145.

RosensonJ,SmollinC,SporerKA,BlancP,OlsonKR.Patternsofecstasy-associatedhyponatremiainCalifornia.AnnEmergMed2007;49(2):164-71.

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Markyourcalendars.TheUPCCbiennialPoisonControlUpdateConferencewillbeheldinSaltLakeCityonMay29thandinRichfieldonJune5th,2008.Thisconferenceisdesignedforpublichealthadvocates,suchasnurses,healtheducators,pharmacists,andotherpublicsafetyprofessionals.Someofthetopicstobecoveredattheconferenceincludepoisoningsinvolvinglead,arsenic,caffeine,handsanitizers,aswellascurrenttrendsinprescriptiondrugabuse.TheconferencebrochurewillbemailedoutinJanuary2008andwillbeavailableonourwebsite.

bIEnnIALUPDATECOnfErEnCE

Mushroompoisoningsareincreasingworldwidesecondarytothegrowingpopularityofpickingwildmushroomsforfoodorfortheirpsychedelicproperties.1Unfortunately,differentiatingpoisonousmushroomsfromedibletypesisquitedifficult,evenforexperts.Manytypesoftoxins,andthereforetoxidromes,areassociatedwithpoisonousmushroomsmakingthediagnosischallenging.Inaddition,growthconditions,decay,ingestionamountandindividualsusceptibilitiescanaffecthowsymptomaticpatientsbecome.Mostcommonly,patientsdevelopself-limitednausea,vomitingandabdominalpainfollowingingestion.However,certainspecies,suchasAmanitaphalloides,arehighlypoisonousandcanbefatal.Somemushroomtoxinshavedelayedeffects,causingsymptomsdaysfollowingingestion.Diazsuggestedaclassificationsystembasedononsetofsymptomsandtargetorgansforidentificationanddiagnosis:Early-onset(<6hrs):neurotoxic,allergicandgastrointestinal;Late-Onset(6-24hrs):hepatotoxic,nephrotoxicanderythromelalgia;andDelayed-Onset(>1day):nephrotoxic,rhabdomyolyticandneurotoxic.Subgroupswithspecificmushroomspeciesarelistedforeachtoxidrome.1Anypatientwithsymptomsdeveloping6ormorehoursafteringestionshouldbeseenintheemergencydepartment.WhitemushroomcapswithwhitegillsareconcerningforthehighlypoisonousAmanitaphalloidesandshouldbeevaluatedforlivertoxicity.Ifpossible,themushroomoritsspores,whichmaybeobtainedfromgastriclavage,shouldbeidentifiedbyamycologist.Treatmentincludesgastricdecontaminationwithlavageandactivatedcharcoalandsupportivecare.Patientspresentingwithsignsofhepaticorrenalfailureshouldbetransferredtoafacilitycapableofperforminghemodialysisandlivertransplantation.CasereportsofhepaticfailurefromAmanitasp.thatimprovedwithN-acetylcysteine,benzylpenicillin,silibinin(anextractofmilkthistle)andcimetidinehavenotbeensupported

bycontrolledresearch.2Obtainingliverfunctiontests,renalfunctionpanelandcreatininekinaseforupto2weekscanhelptorule-outpathologyinpatientswhomayhaveingestedmushroomsassociatedwithdelayed-onsettoxins.TheUtahPoisonControlCenterisavailabletohelpwithmushroomidentification,evaluationandtreatmentrecommendations.

(cont. from pg. 1) Tramadol

3.8%hadtwoseizuresand11.5%ofpatientshadmultipleseizures.1Inthisseries,almostallpatientshadaseizurewithin6hoursoftheingestionwiththemajorityofpatientsseizingwithin2hoursoftheingestion.1Seizureswerereportedmorefrequentlyinagroupofdrugandtramadolabusers.3Thetreatmentofatramadoloverdoseisprimarilysupportive.Activatedcharcoalmaybeconsideredforpatientsthatpresentwithin1-2hoursafteringestion.Naloxonemaybeeffectiveinreversingrespiratorydepression.Benzodiazepinesareindicatedforthetreatmentofseizures.Naloxoneisnoteffectiveintreatingtramadol-inducedseizures.Patientsshouldbemonitoredforaminimumof6hoursandpossiblylongerfollowingingestionoftheextended-releasepreparation.Anacetaminophenconcentrationshouldbeobtainedonallpatientswhohaveintentionallyoverdosedorabusedtramadol.Tramadolisauniqueanalgesicwithopiateandnon-opiateeffects.PleasefeelfreetoconsultwiththestaffoftheUPCCforassistanceinmanagingapoisoningoroverdose.

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TOXICOLOGYTODAY www.utahpoisoncontrol.org

references

MarquardtKA,AlsopJA,AlbertsonTE.Tramadolexposuresreportedtostatewidepoisoncontrolsystem.AnnPharmacother2005;39:1039-1044.

SpillerHA,GormanSE,VillalobosD,etal.Prospectivemulticenterevaluationoftramadolexposure.JToxicolClinToxicol1997;35(4):361-4.

Jovanovic-CupicV,MartinovicZ,NesicN.Seizuresassociatedwithintoxicationandabuseoftramadol.ClinicalToxicology2006;44:143-146.

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P O I s O n P E A r l s

mUshrOOmPOIsOnInGby Anna McKeone, MD

Emergency Medicine Resident

references

DiazJH:Evolvingglobalepidemiology,syndromicclassification,generalmanagement,andpreventionofunknownmushroompoisonings.CritCareMed2005;33(2):419-26.

Tong,TCetal:Comparativetreatmentofalpha-amanitinpoisoningwithN-acetylcysteine,benzylpenicillin,cimetidine,thiocticacid,andsilybininamurinemodel.AnnEmergMed.2007;50(3):282-8.

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E - n E w s l E t t E r

TOXICOLOGYTODAYDIsTrIbUTEDvIAEmAIL!YoucanregistertoreceivethisnewsletterviaemailbyvisitingthenewsletterregistrationpageontheUtahPoisonControlCenterwebsiteat:www.utahpoisoncontrol.org/newsletters.Don’tmissanyexcitingissues!Ifyouhavequestions,needassistanceregisteringoryoudon’thaveemail,pleasefeelfreetocallusat(801)587-0600.

All“emergency”callstotheUPCCarerecorded.Thedigitalrecordingbecomespartofthepatient’smedicalrecord.Digitalrecordingsarevaluableintrainingnewemployeesandareanintegralpartofourcontinuousqualityimprovementprogram.

TELECOmmUnICATIOnsAnDThEUPCC

PhotocourtesyofUSUExtension.ThankyoutoMaggieWolfandMichaelPiep.Photographer:CraigPoulson

Amanita muscaria

UTAhPOIsOnCOnTrOLCEnTErsTAff

DirectorBarbara Insley Crouch, PharmD, MSPH

Medical DirectorE. Martin Caravati, MD, MPH

Associate Medical DirectorDouglas E. Rollins, MD, PhD

Assistant DirectorsHeather Bennett, MPAScott Marshall, PharmD, CSPI*

Administrative AssistantJulie Gerstner

specialists in Poison InformationKathleen T. Anderson, PharmD, CSPI*Michael Andrus, PharmDBradley D. Dahl, PharmD,CSPI*Michael L. Donnelly, RN, BSN, CSPI*Craig Graham, RN, BSNMo Mulligan, RN, BSN, JDEd Moltz, RN, BSN, CSPI*Sandee Oliver, RN, BSN, CSPI*

Micah Redmond, RN, BSNCathie Smith, RN, BSNJohn Stromness, BS Pharm, RPh, CSPI*

Poison Information ProvidersMegan GlanvilleMonique HallChristine HolmanKaren Thomas

Outreach Education ProviderMarty C. Malheiro, MS, CHES

Assistant Education ProviderSherri Pace, BS, CHES

EditorsE. Martin Caravati, MD, MPHBarbara Insley Crouch, PharmD, MSPH Please send comments and suggestions for future articles to the editor of Toxicology Today at:

585 Komas Dr., suite 200salt lake City, Utah 84108

Or send e-mail to poison@hsc.utah.edu

*CSPI denotes Certified Specialist in Poison Information.

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TOXICOLOGYTODAY Administrative: (801) 587-0600

t O x I n s I n t h E n E w s

ThAnkYOU

The Utah Poison Control Center expresses its sincere thanks to the health care professionals, public health officials and toxicology

colleagues that work together to treat and prevent poisonings.

M E E t t h E U P C C s t A f f

Dr.E.mArTInCArAvATIistheMedicalDirectoroftheUtahPoisonControlCenterandattendingtoxicologistattheUniversityHospitalandPrimaryChildren’sHospital.Hereceivedamedicaldegreefrom

theMedicalCollegeofVirginia.HisresidencytraininginemergencymedicinewascompletedatCarolinasMedicalCenterinCharlotte.Heobtainedamaster’sdegreeinPublicHealthattheUniversityofUtahandisboardcertifiedinbothemergencymedicineandmedicaltoxicology.HeiscurrentlySecretary-TreasurerfortheAmericanAcademyofClinicalToxicologyandanAssociateEditoroftheAnnalsofEmergencyMedicine.Heisaco-authorofthetextbook,MedicalToxicology.Whennotsolvingtoxicologicalmysteries,heenjoysfly-fishing,traveling,basketball,hikinganddarkchocolate.Favoritepoisons:arsenic,mercury,ethyleneglycol,acetaminophen.

Home Lead Test Kits Unreliable:TheU.S.ConsumerProductSafetyCommission(CPSC)testedcommonlyavailablehomeleadtestkitsonavarietyofpaintsandotherproductscontainingdifferentlevelsoflead.Of104totaltestresults,morethanhalf(56)werefalsenegatives,andtwowerefalsepositives.Basedonthestudy,consumersshouldnotuseleadtestkitstoevaluateconsumerproductsforpotentialleadhazards.

Haloperidol IV: UpdatedlabelingincludesWARNINGSstatingthatTorsadesdePointesandQTprolongationhavebeenobservedinpatientsreceivinghaloperidol,especiallywhenthedrugisadministeredintravenouslyorinhigherdosesthanrecommended.Haloperidolisnotapprovedforintravenoususe.Dietary Supplements for Erectile Dysfunction - Dangerous Ingredients:ThedietarysupplementsActra-Rx,Axcil,Desirin,EnergyMax,Libidus,Liviro3,Nasutra,Neophase,RhinoVMax,TrueMan,V.Max,Vigor-25,Zencore,Zimaxx,or4EVERONmaycontainanalogsofsildenafil,tadalafil,orvardenafil.Theseagentsaremarketedonwebsitesasnaturalproductsforerectiledysfunctionorsexualenhancement.ThelabelingdoesnotmentiontheseingredientsandtheFDAconsiderstheseproductstobeillegaldrugs.