medical countermeasures pharmacology€¦ · medical countermeasures pharmacology g. zeldes, md ......
TRANSCRIPT
MedicalCountermeasuresPharmacology
G.Zeldes,MD,PharmDMED/OM
OfficeDirector,StrategicMedicalPreparednessU.S.DepartmentofState
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AGENDA
ATNAAsCANAsAntibacterialAgentsImmunoprophylaxis
LogisticsKits/MCM– TheMissingManual
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WhyWorryAboutMCM?(MedicalCountermeasures)
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ATNAACANAAntidoteTreatment- NerveAgent,Auto-Injector ConvulsiveAntidote,NerveAgent
atropine2mgdiazepam10mgpralidoxime600mg transitioningtomidazolam?
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ATNAAPharmacologyAntidoteTreatment- NerveAgent,Auto-Injector
Acetylcholine
From:http://tmedweb.tulane.edu/pharmwiki/doku.php/cholinesterase_inhibitors_-_medical_use_wmd5
PharmacologicTreatmentforNerveAgentExposure
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• Atropinetherapyisguidedbyclinicalsignsandsymptoms.– Titratedosingtothedesiredclinicaleffect.– Goalsaretodrysecretionsandeliminatebronchoconstriction.• Heartrateandpupilsizearepoorclinicalindicatorsofadequateatropinization.• Tachycardiashouldnotdissuadetheclinicianfrominitiatingorcontinuingatropine.• Miosis maybeabsentordelayedindermalexposuresandisnotreversedbysystemicatropine.
• Pralidoxime therapyisguidedbyclinicalsignsandsymptoms.– Titratedosingtothedesiredclinicaleffect.– Goalistoreverseparalysis.– OximesbindtothenerveagentmoreavidlythanAChE toreactivatethenerve
agent–inhibitedenzyme.Reactivationisimpossibleoncedealkylation or"aging"ofphosphorylatedAChE occurs.• Onceagingoccurs,newAChE mustbesynthesized.• Therateofagingvariesamongnerveagents.Agingoccurswithin2minutesaftersoman exposure,5-8hours
aftersarinexposure,andmorethan40hoursaftertabun andVXexposure.
Source:http://emedicine.medscape.com/article/829454-overview#a4
RepeatDosesforNerveAgentExposure
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Itdepends….
RepeatDosesforNerveAgentExposure
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• Atropinetherapyisguidedbyclinicalsignsandsymptoms.• Upto20mgofatropinemayberequiredthefirstday• IntheTokyosarinattack,only19%ofpoisonedpatientsrequiredmorethan2mgofatropine.Severelypoisonedpatientsrequired1.5-15mgofatropine.
• Pralidoxime therapyisguidedbyclinicalsignsandsymptoms.• Iftoxicitypersistsorworsensclinically,administerrepeat
dosesof2-PAMathourlyintervals.IntheTokyosarinattack,severelypoisonedpatientsrequired1-36g.• Pralidoxime-inducedhypertensionhasbeentreatedbyadministering
phentolamine 5mgintravenously,repeatedifnecessaryduetophentolamine'sshortdurationofaction.
Source:http://emedicine.medscape.com/article/829454-overview#a4
SymptomsandMedicalManagementofBacterialAgents
BacterialAgent Signs/Symptoms MedicalManagement
AnthraxBacillusanthracis
Fever, malaise,cough,shortnessofbreath,cyanosis
ciprofloxacin
PlagueYersiniapestis
Highfever,chills,headache,cough,shortnessofbreath,cyanosis
streptomycin
BrucellosisBrucellasp.
Fever,headache,myalgias,sweat,chills
doxycycline
CholeraVibriocholerae
Massivewaterydiarrhea fluidtherapyandantibiotics(tetracycline,doxycycline,orciprofloxacin
TularemiaFrancisella tularensis
Localulcer,lymphadenopathy fever,chills,head-ache,andmalaise
streptomycin
QfeverCoxiella burnetii
Fever,cough,andpleuriticchestpain
tetracycline
Source:http://www.cs.amedd.army.mil/FileDownloadpublic.aspx?docid=5154826d-0f56-4d5f-b46e-8f090e11d80d 9
SymptomsandMedicalManagementofViralAgents
ViralAgent Signs/Symptoms MedicalManagement
VEEVenezuelanequineencephalitis
Feverandencephalitis Nonspecific/supportivecare
Smallpox Malaise,fever,rigors,vomiting,headachefollowedbypustularvesicles
Antiviralunderinvestigation/supportivecare
VHFviralhemorrhagicfever
Flushingoftheface,petechiae,bleeding,fever,myalgias,vomiting,anddiarrhea
Nonspecific/supportivecare
Source:http://www.cs.amedd.army.mil/FileDownloadpublic.aspx?docid=5154826d-0f56-4d5f-b46e-8f090e11d80d 10
BiowarfareAgentsClassification
• LethalAgents (Bacillusanthracis, Francisellatularensis,Botulinumtoxin)
or• IncapacitatingAgents (Brucellasuis,Coxiellaburnetii,Venezuelanequineencephalitisvirus,StaphylococcalenterotoxinB)
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MCMAntibiotics• Ciprofloxacin 500mg
– Ciprofloxacin isa broad-spectrumantibiotic thatisusedtotreatanthraxorplague.ThebactericidalactionofciprofloxacinresultsfrominhibitionoftheenzymeswhicharerequiredforbacterialDNAreplication,transcription,repair,andrecombination.
• Doxycycline 100mg– DoxycyclinehasbacteriostaticactivityagainstabroadrangeofGram-positive
andGram-negativebacteria. Doxycyclineinhibitsbacterialproteinsynthesisbybindingtothe30Sribosomalsubunit.
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BroadSpectrumAntibiotics• Levofloxacin 750mg
– Levofloxacinisa broad-spectrumantibiotic thatisbactericidalagainstboth Gram-positive and Gram-negative bacteria.ThemechanismofactioninvolvesinhibitionofbacterialtopoisomeraseIVandDNAgyrase,enzymesrequiredforDNAreplication,transcription,repairandrecombination.
• Clindamycin900mg– Clindamycinhasaprimarily bacteriostatic effectagainstaerobic Gram-
positive cocci&anaerobic, Gram-negative rod-shapedbacteria.MostaerobicGram-negativebacteriaareresistanttoclindamycin.Itisabacterialproteinsynthesisinhibitorbyinhibitingribosomaltranslocationbybindingtothe50SrRNA ofthelargebacterialribosomesubunit.
• Meropenem1gram– Meropenemisa broad-spectrumantibiotic thatisbactericidalagainst
both Gram-positive and Gram-negative bacteria.Itinhibitsbacterialwallsynthesislikeotherβ-lactamantibiotics.Incontrasttootherbeta-lactams,itishighlyresistanttodegradationby β-lactamases orcephalosporinases.
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Immunoprophylaxis
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Immunoprophylaxis(Vaccines)
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Kits– Quantity• LimitedCentralFunding
– Postsreceivedkitsbasedonpostsize– Arbitrarilydividedintosmall,medium,andlarge
• WhoDecidesifPostNeedsMoreKits?– JointdecisionbetweenhealthunitandRSO– Ifyouneeda“secondopinion”thenRMO,RMM,andOfficeDirector,
SMP
• BasedonWhat?– Postsizeandphysicallayout– Postcensusandlikelynumbertobeexposed– Hostcountryresources– Postthreatstatus
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Kits– Quantity
• WhatifPostNeedsMoreKits?
– Additionalvehicle,basictraumaandadvancedtraumakitscanbeorderedatpostexpensefromBoundTreeMedical
–Mustcalltoorder,notavailableonline– Postresponsibleforreplenishmentsofanyadditionalkitsordered
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WhereShouldIStoreThisKit?
• LocationofkitswithinapostshouldbeajointdecisionbetweenthepostmedicalproviderandtheRSO.
• Consider:– postphysicalsize,totalpopulation,andgeography– kitsize,function,andquantity– likelihoodofneedforkitcontents
• highthreatpost?,earthquakefaultline?,etc.– whowillusethekit?
• providerorlayperson?
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MCMBagLocation
• PostSpecific• Containsitemstobeusedonlybyproviders(notlayperson)
• HealthUnit- administertoanexposedpatientandcan’tbeusedbynon-providers,sostoreitwhereeveryoufindconvenientandcouldgettoiteasilyintheeventyouwillneedthecontents.
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HowDoIKnowWhoIsResponsibleforKitReplenishment?
• AdditionalHealthUnitKitResponsibilities– Coordinatesmaintenance&replenishmentsforcentrallyfundedkits
• Healthunitvs.otherdepartmentorigin• Centralvs.postfunding• Oldvs.newkit• OMvs.postfundedsource• CentrallyfundedreplenishmentofOMprovidedstandardizedkitdependentonIDtagnumberfoundonnewkits
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• Willbetrackedcentrallyforcentrallyfundedkits
• Tomanagefunds,afieldingplanhasbeendevelopedwhichwillreplaceapproximately1/3ofthekitseachyear
• Althoughwejustfieldednewkitslastyear,someofyouwillreceivereplacementkitsthisyear(pleasebepatientandunderstandingduringthisinterimperiod!)
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HowDoIKnowWhenItIsTimeforKitReplacement?
• StandardizedRMUKwillconsistof8smallerPelikan cases• Duringtheseveralyeartransitionperiod,youmayreceivea
RMUKreplenishmentshipmentbeforeyoureceivethenewcasesoryoumayreceiveemptycasesbeforeyoureceivereplenishments
• Duringthetransition,pleasereplacetheoldRMUKcontainercontentswiththenewcontentsifyouhaven’treceivedthenewPelikan casesyet.YouarefreetousetheoldRMUKcontents/containersinanywaythatmakessenseforyourpost.
• Pleasebepatientandunderstandingduringthisinterimperiod!
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WhatAbouttheRMUKs?
HowDoIKnowifSomethingisMissingFromaKitsShipment?
• Checkthepackinglistinsidethebox.Doesitindicatethatsomeitemswerenotshippedorwillbeshippedlaterorseparately?
• Ifyoubelievethatsomethingthatshouldbeintheboxisnot,thenpleasecontactMEDOMEP– Kits(DaveHillormyself)toreportthediscrepancyandforfurtherinvestigation
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MedicalCountermeasuresReminder
• Relenzahasbeenreplacedwithperamivir• WhenyourMCMsupplyofRelenzaisexpired,itcanbediscarded/destroyed
• YouwillNOTreceiveanyRelenzareplenishmentsfromMED/OM
• IfyouhavefoundRelenzausefultotreathealthunitpatients,thenyoushouldconsiderorderingahealthunitsupplywithpostfunds
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MedicalCountermeasuresReminder
• ThehealthunitisresponsibleforallATNAAunitsdistributedthroughoutapost/region
• Pleasekeeptrackofinventorybyrecordingthelotnumber,quantityandlocationofallATNAAunitsthatyouhavedistributed
• PleaseassignaPOCforthehealthunitwhowillserveastheinterfacebetweenOM/SMPandtheRSO/MOinremoteATNAAlocations
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SLEPFunFactsShelfLifeExtensionProgram
• MCMstockpileddrugsarenottobeusedforroutinehealthunitpatientcare
• Becausethereisno“rotation”ofthestockeddrugsoutofthestockpile,everyseveralyears,thedrugswillstayinthestockpilepasttheirexpirationdate
• Veryexpensivetoreplacestockpileddrugseverytwoorthreeyears
• Expirationdatedoesnotindicatewhenthedrugwilllosepotency,butratherthatthedrugwillmaintainpotencyatleastthroughthatdate
• Retestingforpotencyandstabilitycanextendtheexpirationdate
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SLEPFunFactsShelfLifeExtensionProgram
• SLEPadministeredbytheArmy• TestingdonebytheFDA• NotalldrugsareenteredintheSLEP– Ciprofloxacin,doxycycline,Tamiflu,ATNAA,CANAareinSLEP
• CostsmoneytoparticipateinSLEP,buttotalcostmuchlessthanpurchasingreplacements
• Costsmoneytoprintupdatedlabels,pleasekeepyourinventoriesuptodate
• CurrentlyonlySLEPadministratorshavedirectaccesstotheSLEPdatabase
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SLEPatPostShelfLifeExtensionProgram
• Don’tdestroyanySLEPdrugsuntilyouareinstructedtodiscardspecificlotnumbersbyOM
• Ifyouarenotsureaboutthestatusofaparticularlotnumber,[email protected] forclarification– Alwaysincludedrugname,lotnumberandquantityinyouremail
• PleasecontinueupdatingyourquarterlyinventoriesofMCMintheEMPdatabase(onlineversioncurrentlyunavailable,pleaseemaildatatoaboveaddress)
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HowDoIKnowWhentoUsetheMCMDrugs?
Althoughyoumayfeelisolated,thereareMEDresourcesyoushouldbeconsultingearly–MP– RMO– RMM– Dr.Martin,Chief,InfectiousDisease– Dr.Walters,Director,OperationalMedicine– Dr.Zeldes,OfficeDirector,StrategicMedicalPreparedness
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HowDoIKnowWhentoUsetheMCMDrugs?
PurposeofearlyMEDConsultation– Accessmedicalintelligencetoplaceyoursuspectedincidentintocontext
– FacilitatesDr.Martinmakingrecommendationsforfurtheraction
– FacilitatesOM/SMPwithlogisticalsupport– FacilitatesOMmakingarrangementsformedevacifindicated
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StoringControlledSubstancesintheHealthUnit
Followspiritoftheregulations!SecurityRequirementsForPractitioners
Practitionersincludephysicians,dentists,veterinarians,researchers,hospitals,pharmacies,orotherpersonsregisteredtodoresearch,todispense,ortouseinteachingorchemicalanalysisacontrolledsubstanceinthecourseofprofessionalpractice.
Minimumsecuritystandardsforpractitionersaresetforthintheregulations(Title21CFR1300 toend)andaretobeusedinevaluatingsecurity.Theymaynotnecessarilybeacceptableforprovidingeffectivecontrolsandoperatingprocedurestopreventdiversionortheftofcontrolledsubstances.Forexample,ahospitalthatkeepslargequantitiesofcontrolledsubstancesonhandmayneedasafeorvaultsimilartotherequirementsforadistributor.Thesamereasoningalsoappliestootherpractitioners.
Apractitioner'soverallsecuritycontrolswillbeevaluatedtodetermineiftheymeettheintentofthelawandregulationstopreventtheftordiversion.
https://www.deadiversion.usdoj.gov/pubs/manuals/sec/sec_req.htm
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StoringControlledSubstancesintheHealthUnit
MinimumStandardsforPractitioners'HandlingofControlledSubstances
Controlledsubstancesmustbestoredinasecurelylockedcabinetofsubstantialconstruction.Pharmacieshavetheoptionofstoringcontrolledsubstancesassetforthabove,orconcealingthembydispersalthroughouttheirstockofnon-controlledsubstances.
EventhoughtheFederalregulationsdonotspecificallydefinelockedcabinetconstruction,theintentofthelawisthatcontrolledsubstancesmustbeadequatelysafeguarded.Therefore,dependingonothersecuritymeasures,awoodencabinetmayormaynotbeconsideredadequate.Inanareawithahighcrimerate,astrongmetalcabinetorsafemayberequired.
Someofthefactorsconsideredwhenevaluatingapractitioner'scontrolledsubstancessecurityinclude:1. Thenumberofemployees,customersand/orpatientswhohaveaccesstothecontrolledsubstances.2. Thelocationoftheregistrant(highorlowcrimearea).3. Useofaneffectivealarmsystem.4. Quantityofcontrolledsubstancestobekeptonhand.5. Priorhistoryoftheftordiversion.
https://www.deadiversion.usdoj.gov/pubs/manuals/sec/sec_req.htm
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ParenteralPainMedicationNursingProtocol
•Comingsoonfor….»Ketamine»Morphine»Diazepam
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LogisticCommunication
• Twogroupemailaddresses:
o MEDOMEP– KITSo MEDOMEP- MCM/PEP
• PleasefillinyourKits/MCMsurvey
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Summary
ATNAAsCANAsAntibacterialAgentsImmunoprophylaxis
LogisticsKits/MCM– TheMissingManual
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