final mstudymguid
e
NR 566 final study guide
m m m m
Chapter 18: Drugs Affecting the Hematopoietic System
m m m m m m
• Knowmthempharmacodynamics,mpharmacotherapeuticsmclinical muse,mdrug minteractionsmandmadver
semdrugreactionsmfor:
Anticoagulants
• Pharmacodynamics
• Oralmanticoagulantsmsuchmasmwarfarinm(Coumadin)minhibitmthemhepaticmsynthesismofmseveralmclotti
ngmmfactors,including mfactor mX.m
• Heparinminhibitsmthemactivitymofmseveralmactivatedmclotting mfactorsmbymaccelerating mthemactivit
ymofmantithrombinmIII.m
• LMWHmenoxaparinm(Lovenox)mpotentiatesmthemactivitymofmantithrombinmIIImandminactivatesmfactorsmXam
andmIIam(thrombin).m
• Dabigatranm(Pradaxa)mismamdirectmthrombinminhibitor.m
• Thrombinmismrequiredmformthemconversionmofmfibrinogenmtomfibrinminmthemclotting mm
cascade,mthusmdabigatran'sminhibitionmofmthrombinmpreventsmthrombimfrommformi
ng.m
• Fondaparinuxm(Arixtra)mismamselectiveminhibitor mofmantithrombinmIIImandmamfactor mXaminhibitor.m
• Rivaroxabanm(Xarelto)manmanticoagulant,mismamhighlymselectivemfactor mXaminhibitor mthatminhibitsmthrom
bin formationmandmthemdevelopmentmofmthrombi.m
• Apixabanm(Eliquis)mismamselectiveminhibitor mofmfactor mXa.
• Aspirinmantagonizesmthemcyclooxygenasempathwaymandminterferesmwithmplateletmaggregation.
• NSAIDsmhavemthismsamemaction.m
• NSAIDsmaremnotmusedmasmantiplateletmdrugs,mbutmthismexplainsmwhymconcurrentmusem
withmanticoagulantsmismcontraindicated
• Ticlopidinem(Ticlid)mandmclopidogrel m(Plavix)mreducemplateletmaggregationmbyminhibiting mthemADPmpathwa
yofmplatelets.m
• Unlikemaspirin,mtheymhavemnomeffectmonmprostaglandinmmetabolism.m
• Ticagrelor m(Brilinta)mreversiblyminteractsmwithmthemplateletmP2Y12mADP-
receptor mtompreventmplateletmactivation.m
• Vorapaxar m(Zontivity)mismamprotease-activatedmreceptor-1m(PAR-1)mantagonist,minhibiting mthrombin-
inducedmandmthrombinmreceptor magonistmpeptide-inducedmplateletmaggregation
• Pharmacotherapeutics:
,final mstudymguid
e
• PrecautionsmandmContraindications
• Allmanticoagulantsmaremcontraindicatedmfor mpatientsmwhomaremhypersensitivemtomthemdrug mormacti
velymbleeding mormwhomhavemhemophilia,mthrombocytopenia,mseveremHTN,mintracranialmhemorrha
ge,mminfectiveendocarditis,mactivemtuberculosis,mormulcerativemlesionsmofmthemGImtract.m
• Heparinsmaremcontraindicatedminmadvancedmhepaticmormrenalmdisease.m
• Theymmaymbemusedminmpatientsmwhomaremactivelymbleeding mtomtreatmDICm
• HeparinmismPregnancymCategorymC:mstillbirth,mprematurity
• Somemheparinmpreparationsmcontainmbenzylmalcohol:mknownmtomcausem“gasping msyndrome”:m
• fatalmtoxicityminmneonates
• Hyperkalemia mmaymdevelop
,final mstudymguid
e
• Usemfor mpatientmwithmDMmormrenalminsufficiencymrequiresmcaremandmfrequentmmonitoring mofmaPTT
• Hasmbeenmassociatedmwithmfatalmmedicationmerrorsmr/tmdifferentmstrengthsmofmpreparations
• JCo:manticoagulantmtherapymismamNationalmpatientmSafetymGoal:mplanminmplacematmeachmfacilit
ymtomreducempatientmharm
• LMWHsmaremcontraindicatedmformpatientsmwithmallergiesmtompork,msulfites,mormbenzylmalco
hol;muncontrolledbleeding;mandminmpatientsmwhomhavemantiplateletmantibodies
• Renalmimpairment:mcautiousmuse
• Bodymweightmlessmthanm50mkgmassociatedmwithmincreasedmr/fmbleeding:
• enoxaparinmdosemadjustment
• Cautiousmuse:muntreatedmHTN,mretinopathym(HTNmormDMmcaused),mseveremliver mdisease,mrecent
m Hxm ofm ulcer,m or m malignancy
• Notmusedmformthromboprophylaxisminmpatientsmwithmmechanicalmheartmvalues:mespecia
llympregnant(r/fmheartmvaluemthrombosis)
• Enoxaparin:mPreg mCatmB,mtinzaparin:mteratogenicitymandmfetalmdeath,mfondaparinux:mPreg mB
• Firstmlinemdrug mformwomenmwhomrequiremantithromboticmtherapymduring mpregnancy:mLMWH
• PharmacokineticsmofmLMWHmismalteredmduring mpregnancy
• Warfarin
• Hepaticmdysfunctionmpotentiatesmresponsemthroughmimpairedmsynthesismofmcoagulationmfactors
• Usemwithmcaution:mHypermetabolicmstatesmproducedmbymfever mormhyperthyroidis
mmincreaseresponsivenessmtomwarfarin:
• r/tmincreasedmcatabolismmofmvitmKmdependentmcoagulationmfactors
• Increasedmr/fmbleeding minmolder madults
• Cautionmusembasedmonmbalancembetweenmpotentialmfor mdecreasedmr/fmthromboemboli
smmandthemriskmfor mbleeding mespeciallyminmthosemwithmdementiamormseveremcognitivemi
mpairment:mHxmofmthreemfallsminmthempreviousmyearmormrecurrentminjuriousmfalls,munco
ntrolledmHTN,mormnon-adherentmormunreliable
• Warfarin mismPregnancy mCategorymX:mCrossesmplacentamandmcanmcausemhemorrhagicmdisorder
sminmthemfetusmandmseriousmbirthmdefects
• Safemduring mlactation
• Rivaroxabanm(Xarelto):mBlack-
BoxmWarning:mprematuremdiscontinuationmofmanticoagulantsmincluding mrivaroxabanmmaymleadmtomt
hromboticmevents.m
• Anmincreasedmriskmofmstrokemismseenminmpatientsmwithmatrialmfibrillationmwhenmtransitioni
ng mmtowarfarinm
• RivaroxabanmismPregnancymCategorymC mandmismnotmrecommendedmfor museminmpregnantmwomen.
• Apixabanm(Eliquis):mBlackmBoxmwarning mprematuremdiscontinuationmleading mtomthromboticmevents
• Althoughmtheremaremnomwell-controlledmstudies:mPregnancymCategorymB
• Hypersensitivitymtomaspirinmandmcross-sensitivitymwithmNSAIDsmmaymoccur,mcontraindicating mthemdrug
• Aspirinmhypersensitivitymismmoremprevalentminmpatientsmwithmasthma,mnasalmpolyps,m
ormmchronicurticaria.m
• Reyemsyndromemhasmbeenmassociatedmwithmitsmuseminmchildrenmandmteenagersmwhomhaveminflue
nzammorchickenpox.
• Reversiblemhepatotoxicitymhasmoccurred
• Usemwithmcautionminmliver mdamage,mpreexisting mhypoprothrombinemia,mormvitmKmdeficiencym
• Preg mCatmCmandmCatmDminmthirdmtrimester
• Avoidmduring mlactation
• Clopidogrel mandmticlopidine:mseveremhepaticmdiseasem(r/fmbleeding md/o),mdomnotmuseminmthesempatients
• NotmrecommendedmformpatientsmwithmGImd/o
,final mstudymguid
e
• Preg mCategorymB
e
NR 566 final study guide
m m m m
Chapter 18: Drugs Affecting the Hematopoietic System
m m m m m m
• Knowmthempharmacodynamics,mpharmacotherapeuticsmclinical muse,mdrug minteractionsmandmadver
semdrugreactionsmfor:
Anticoagulants
• Pharmacodynamics
• Oralmanticoagulantsmsuchmasmwarfarinm(Coumadin)minhibitmthemhepaticmsynthesismofmseveralmclotti
ngmmfactors,including mfactor mX.m
• Heparinminhibitsmthemactivitymofmseveralmactivatedmclotting mfactorsmbymaccelerating mthemactivit
ymofmantithrombinmIII.m
• LMWHmenoxaparinm(Lovenox)mpotentiatesmthemactivitymofmantithrombinmIIImandminactivatesmfactorsmXam
andmIIam(thrombin).m
• Dabigatranm(Pradaxa)mismamdirectmthrombinminhibitor.m
• Thrombinmismrequiredmformthemconversionmofmfibrinogenmtomfibrinminmthemclotting mm
cascade,mthusmdabigatran'sminhibitionmofmthrombinmpreventsmthrombimfrommformi
ng.m
• Fondaparinuxm(Arixtra)mismamselectiveminhibitor mofmantithrombinmIIImandmamfactor mXaminhibitor.m
• Rivaroxabanm(Xarelto)manmanticoagulant,mismamhighlymselectivemfactor mXaminhibitor mthatminhibitsmthrom
bin formationmandmthemdevelopmentmofmthrombi.m
• Apixabanm(Eliquis)mismamselectiveminhibitor mofmfactor mXa.
• Aspirinmantagonizesmthemcyclooxygenasempathwaymandminterferesmwithmplateletmaggregation.
• NSAIDsmhavemthismsamemaction.m
• NSAIDsmaremnotmusedmasmantiplateletmdrugs,mbutmthismexplainsmwhymconcurrentmusem
withmanticoagulantsmismcontraindicated
• Ticlopidinem(Ticlid)mandmclopidogrel m(Plavix)mreducemplateletmaggregationmbyminhibiting mthemADPmpathwa
yofmplatelets.m
• Unlikemaspirin,mtheymhavemnomeffectmonmprostaglandinmmetabolism.m
• Ticagrelor m(Brilinta)mreversiblyminteractsmwithmthemplateletmP2Y12mADP-
receptor mtompreventmplateletmactivation.m
• Vorapaxar m(Zontivity)mismamprotease-activatedmreceptor-1m(PAR-1)mantagonist,minhibiting mthrombin-
inducedmandmthrombinmreceptor magonistmpeptide-inducedmplateletmaggregation
• Pharmacotherapeutics:
,final mstudymguid
e
• PrecautionsmandmContraindications
• Allmanticoagulantsmaremcontraindicatedmfor mpatientsmwhomaremhypersensitivemtomthemdrug mormacti
velymbleeding mormwhomhavemhemophilia,mthrombocytopenia,mseveremHTN,mintracranialmhemorrha
ge,mminfectiveendocarditis,mactivemtuberculosis,mormulcerativemlesionsmofmthemGImtract.m
• Heparinsmaremcontraindicatedminmadvancedmhepaticmormrenalmdisease.m
• Theymmaymbemusedminmpatientsmwhomaremactivelymbleeding mtomtreatmDICm
• HeparinmismPregnancymCategorymC:mstillbirth,mprematurity
• Somemheparinmpreparationsmcontainmbenzylmalcohol:mknownmtomcausem“gasping msyndrome”:m
• fatalmtoxicityminmneonates
• Hyperkalemia mmaymdevelop
,final mstudymguid
e
• Usemfor mpatientmwithmDMmormrenalminsufficiencymrequiresmcaremandmfrequentmmonitoring mofmaPTT
• Hasmbeenmassociatedmwithmfatalmmedicationmerrorsmr/tmdifferentmstrengthsmofmpreparations
• JCo:manticoagulantmtherapymismamNationalmpatientmSafetymGoal:mplanminmplacematmeachmfacilit
ymtomreducempatientmharm
• LMWHsmaremcontraindicatedmformpatientsmwithmallergiesmtompork,msulfites,mormbenzylmalco
hol;muncontrolledbleeding;mandminmpatientsmwhomhavemantiplateletmantibodies
• Renalmimpairment:mcautiousmuse
• Bodymweightmlessmthanm50mkgmassociatedmwithmincreasedmr/fmbleeding:
• enoxaparinmdosemadjustment
• Cautiousmuse:muntreatedmHTN,mretinopathym(HTNmormDMmcaused),mseveremliver mdisease,mrecent
m Hxm ofm ulcer,m or m malignancy
• Notmusedmformthromboprophylaxisminmpatientsmwithmmechanicalmheartmvalues:mespecia
llympregnant(r/fmheartmvaluemthrombosis)
• Enoxaparin:mPreg mCatmB,mtinzaparin:mteratogenicitymandmfetalmdeath,mfondaparinux:mPreg mB
• Firstmlinemdrug mformwomenmwhomrequiremantithromboticmtherapymduring mpregnancy:mLMWH
• PharmacokineticsmofmLMWHmismalteredmduring mpregnancy
• Warfarin
• Hepaticmdysfunctionmpotentiatesmresponsemthroughmimpairedmsynthesismofmcoagulationmfactors
• Usemwithmcaution:mHypermetabolicmstatesmproducedmbymfever mormhyperthyroidis
mmincreaseresponsivenessmtomwarfarin:
• r/tmincreasedmcatabolismmofmvitmKmdependentmcoagulationmfactors
• Increasedmr/fmbleeding minmolder madults
• Cautionmusembasedmonmbalancembetweenmpotentialmfor mdecreasedmr/fmthromboemboli
smmandthemriskmfor mbleeding mespeciallyminmthosemwithmdementiamormseveremcognitivemi
mpairment:mHxmofmthreemfallsminmthempreviousmyearmormrecurrentminjuriousmfalls,munco
ntrolledmHTN,mormnon-adherentmormunreliable
• Warfarin mismPregnancy mCategorymX:mCrossesmplacentamandmcanmcausemhemorrhagicmdisorder
sminmthemfetusmandmseriousmbirthmdefects
• Safemduring mlactation
• Rivaroxabanm(Xarelto):mBlack-
BoxmWarning:mprematuremdiscontinuationmofmanticoagulantsmincluding mrivaroxabanmmaymleadmtomt
hromboticmevents.m
• Anmincreasedmriskmofmstrokemismseenminmpatientsmwithmatrialmfibrillationmwhenmtransitioni
ng mmtowarfarinm
• RivaroxabanmismPregnancymCategorymC mandmismnotmrecommendedmfor museminmpregnantmwomen.
• Apixabanm(Eliquis):mBlackmBoxmwarning mprematuremdiscontinuationmleading mtomthromboticmevents
• Althoughmtheremaremnomwell-controlledmstudies:mPregnancymCategorymB
• Hypersensitivitymtomaspirinmandmcross-sensitivitymwithmNSAIDsmmaymoccur,mcontraindicating mthemdrug
• Aspirinmhypersensitivitymismmoremprevalentminmpatientsmwithmasthma,mnasalmpolyps,m
ormmchronicurticaria.m
• Reyemsyndromemhasmbeenmassociatedmwithmitsmuseminmchildrenmandmteenagersmwhomhaveminflue
nzammorchickenpox.
• Reversiblemhepatotoxicitymhasmoccurred
• Usemwithmcautionminmliver mdamage,mpreexisting mhypoprothrombinemia,mormvitmKmdeficiencym
• Preg mCatmCmandmCatmDminmthirdmtrimester
• Avoidmduring mlactation
• Clopidogrel mandmticlopidine:mseveremhepaticmdiseasem(r/fmbleeding md/o),mdomnotmuseminmthesempatients
• NotmrecommendedmformpatientsmwithmGImd/o
,final mstudymguid
e
• Preg mCategorymB
