1. Diazepam JaneDavidson MSNE 5356AdvancedPharmacology LamarUniversity

2. Diazepam Diazepam isusedtotreatstatusepilepticusandasanadjunct inconvulsive disorders Diazepam depressesalllevelsof theCentralNervousSystemthrough the increasedactionof gamma-aminobutyricacid(GABA) Diazepam isabenzodiazepinethattreats unbalancedchemicalsinthebrain Diazepam isgenerallygivenintherectalform forthepediatricpopulationin treatment of statusepilepticus

3. Epilepsy Epilepsy,alsoknownasseizuredisorderisexcessive and abnormalbraincell activitythatcanoccuratanyageandvaryinetiology Seizurescanbehereditaryor congenitaloracquired There are two classifications of seizures: Partial or generalized Partialconsistsof simpleandcomplex Generalizedconsistsofabsence,tonic-clonic,clonic,atonic, myoclonic, andtonicseizures Statusepilepticusisanothercategory ofseizureactivitythatislife-threatening andisdefinedasactivitylastinggreaterthan30minutes ortwo ormore consecutiveseizureswithoutrecoverybetween them

4. IntendedDrugResponse The primarygoalsoftreatingacuterepetitiveseizuresarepromptcessationof theseizureandpreventionofrecurrence Diazepamexertsitsanticonvulsanteffectbyinteractingwithreceptor molecules,thebenzodiazepinereceptor,toregulatetheefficiencyofthe inhibitoryneurotransmitterGABAattheGABA (A)receptor The GABA(A)complexisareceptor-gatedchloridechannelthatcontainsthe benzodiazepineasanallostericmodulatoryunit Equilibrationspeedbetweenplasmaandtheeffectsiteisdescribedbythe equilibrationhalf-lifemeasuredbyeliminationofthedrugfromtheeffect site.ThedeterminingfactorforonsetofactionintheCNSistheequilibration of thehalf-life. Diazepamcrosses thebloodbrainbarriertoelicititspharmacologicaleffect

5. PotentialDrugInteractions OtherCNSdepressants(e.g.alcohol,barbiturates,andopioids)thatmay causeincreasedtoxicity,sedation,andrespiratorydepression. TagametmaydecreasethemetabolismofDiazepamresultinginan increasedhalf-lifeandadecreaseinclearanceofthedrug. Selectiveserotoninreuptakeinhibitors(e.g.Prozac,Zoloft,Paxil)increase diazepamlevelsandalteritsclearance. Valproicacidmayalsoresultinanincreaseinsedativeeffectsof Diazepambydisplacingitfromitsbindingsites StrongCYP3A4inhibitors(Doxylamine,Hydroxyzine,Fosaprepitant, Minocycline&Olanzapine)alsocausepotentialinteractionswith

6. AdverseDrug Reactions/SideEffects Drowsiness,amnesia,vertigo,hypotension,andslowed respiratoryrate.Otherpossibleadversereactionsnotedare tachycardia, chestpain,confusion, ataxia,slurredspeech,and headache. Common sideeffectsmayincludelightheadedness,rash, constipation,nausea, vomiting,menstrualirregularities,and blurredvision Sedation isacommonlyreportedadverseeventassociatedwith Diazepaminanyroutethatisadministered.This mustbe monitored incomparison tothenormalpost-ictalsedationof

7. Pharmacokinetics Volumedistributionequals0.8-1.9L/kg The percent bound to plasma protein equals 98 where T1/2 equals 44-48hrs. Thoughitaccumulatesovertimeand can takelonger withprolongeduse. Oralbioavailabilityisgreater than90%andtimetopeak ranges from15 minutesto2.5 hours.Iffastingpeak timeis1.5hours and withfood 2.5hours. Metabolismof Diazepamoccursintheliverviaoxidationcatalysed bycytochromeP450(CYP)isoenzymes3A4and2C19 Diazepamshows tohaveadverseeffectsthat affectmore ofthe

8. BindingIssues DuetoDiazepambeinghighlyboundtoplasmaproteins, thebindinginteractionswithotherdrugsarise. Freefattyacidsareanexampleofaclassofdrugsthat displaceDiazepambindinginvitroandinvivo. Valproicacidisadrugthatisatwochainfattyacidand anddisplacesDiazepamwithitsabilitytobindfattyacid bindingsitesonalbumin. The inhibitionofDiazepambindingbyValproicacidis competitiveduetothenumberofbindingsitesfor Diazepam.

9. Pharmacogenomics Drugtreatmentofepilepsyischaracterizedbytheunpredictablyofefficacy,drug reactions,andoptimaldosesinindividualizedpatients. Theunpredictabilityofantiepilepticsresults from individualgenes whose variationsexertameasurable influence on theeffectofthedruggivenfor treatment. Environmental andgeneticfactorsplayaroleinregulationof basal expression andfunctionoftheCYP3A4receptors. Thecurrent beststrategytoavoidgeneticallydose-relatedadverse reactionsis usedof single-dose moderndaytreatment ofantiepileptics whicharenot metabolizedbythelivernorinvolvedinidiosyncraticreactions.

10. ImprovingCommunication Roundingwithallofthedifferentprofessions(inahospital)seemstoworkreallywell as everyonecansharetheirknowledgeinrealtime Improving communicationwouldbeface-to-faceconversationormeetingsconsistingwiththe specialist,primarycarephysician,chargenurse,treatingnurse,nurseassistant,social worker,dietician/nutritionist,therapists,and casemanager Thetreatmentplan establishedwillbe a teamapproach and provideasolidfoundationof communicationbetweenallprofessionsresultingina moreestablishedmeans ofpatient safety Inotherclinicalsettings,thenurseorcaregiverwillplayavitalroleto ensureanymedication adjustments,frequencyorintensityinseizures,seizurepattern,adverseeffects,etc.are communicated withtheprescribingdoctoralongwiththeprimarycarephysician

11. ApplicationtoPractice Patientsandcaregiversmustunderstandthedifferent typesofseizuresandunderstandwhentheyshouldbe promptedtoseekmedicalemergency. Overuseandabusemust be avoidedandadverse reactionsmustfullybeunderstood Collaborationwiththeproviderorprivatedutynurse, otherin-homeresources,andalldoctorsassociated withthechild’scareisimperative. The nurse plays the most important role in this process and must be accountable for the education provided andassessed