Medical Countermeasures Pharmacology€¦ · Medical Countermeasures Pharmacology G. Zeldes, MD ... ordering a health unit supply with post funds 24. ... • MCM stockpiled drugs

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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