Drugs for Coagulation Disorders Andrew N. Schmelz, PharmD Post-Doctoral Teaching Fellow Purdue...
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Transcript of Drugs for Coagulation Disorders Andrew N. Schmelz, PharmD Post-Doctoral Teaching Fellow Purdue...
Drugs for Drugs for Coagulation Coagulation DisordersDisorders
Andrew N. Schmelz, PharmDAndrew N. Schmelz, PharmDPost-Doctoral Teaching FellowPost-Doctoral Teaching Fellow
Purdue UniversityPurdue UniversityOctober 8, 2008October 8, 2008
[email protected]@purdue.edu
ObjectivesObjectives
List important steps of hemostasis and List important steps of hemostasis and fibrinolysisfibrinolysis
Describe thromboembolic disorders that Describe thromboembolic disorders that are indications for coagulation modifiersare indications for coagulation modifiers
Identify the primary mechanism for Identify the primary mechanism for each coagulation modifying-drug each coagulation modifying-drug discusseddiscussed
Match specific coagulation-modifying Match specific coagulation-modifying drugs to lab tests with which they are drugs to lab tests with which they are appropriately monitoredappropriately monitored
Objectives (cont)Objectives (cont)
Categorize coagulation-modifying Categorize coagulation-modifying drugs based on their classification drugs based on their classification and mechanism of actionand mechanism of action
List important adverse effects for List important adverse effects for each coagulation-modifying drug each coagulation-modifying drug discusseddiscussed
Process of HemostasisProcess of Hemostasis
Hemostasis:Hemostasis: Protects the body from Protects the body from both external and internal injuryboth external and internal injury
Injury to blood vessels causes:Injury to blood vessels causes:– Vessel spasms (causing constriction)Vessel spasms (causing constriction)– Platelet adherence to injury sitePlatelet adherence to injury site– Platelets aggregate and form plugPlatelets aggregate and form plug– Insoluble fibrin strands form and Insoluble fibrin strands form and
coagulatecoagulate
Process of HemostasisProcess of Hemostasis
(Factor Xa)
Intrinsic Pathway(In response to injury)
Extrinsic Pathway(Blood enters tissue spaces)
Removal of Blood ClotsRemoval of Blood Clots
FibrinolysisFibrinolysis: Removal of clot so : Removal of clot so that tissue can resume its normal that tissue can resume its normal activityactivity
Diseases of HemostasisDiseases of Hemostasis
Thromboembolic disordersThromboembolic disorders (MI (MI and CVA)and CVA)– Stationary clot (thrombus) grows and Stationary clot (thrombus) grows and
deprives specific areas of oxygendeprives specific areas of oxygen Deep Vein ThrombosisDeep Vein Thrombosis (DVT) (DVT)
– Formation of clots in large veins (usually Formation of clots in large veins (usually legs)legs)
EmbolusEmbolus– Thrombus may break off and be carried Thrombus may break off and be carried
by bloodstream to affect other areasby bloodstream to affect other areas
Diseases of Hemostasis Diseases of Hemostasis (cont)(cont)
ThrombocytopeniaThrombocytopenia– Low number of platelets, cannot Low number of platelets, cannot
properly form clotsproperly form clots HemophiliasHemophilias
– Genetic deficiencies of clotting factorsGenetic deficiencies of clotting factors
Mechanisms of ActionMechanisms of Action
AnticoagulantsAnticoagulants– Inhibition of clotting factorsInhibition of clotting factors
AntiplateletsAntiplatelets– Inhibition of platelet functionInhibition of platelet function
ThrombolyticsThrombolytics– Lyse thrombiLyse thrombi
HemostaticsHemostatics– Inhibition of fibrinolysisInhibition of fibrinolysis
Inhibition of Clotting Inhibition of Clotting FactorsFactors
(Anticoagulants)(Anticoagulants)
HeparinHeparin
ExampleExample: Heparin (Heplock®): Heparin (Heplock®) MOAMOA: Enhances inhibitory effect of : Enhances inhibitory effect of
antithrombin III (inhibits factor Xa)antithrombin III (inhibits factor Xa)
HeparinEnoxaparin
(Factor Xa)
HeparinHeparin
ExampleExample: Heparin (Heplock®): Heparin (Heplock®) MOAMOA: Enhances inhibitory effect of : Enhances inhibitory effect of
antithrombin III (inhibits factor Xa)antithrombin III (inhibits factor Xa) RouteRoute: IV (continuous infusion), SC: IV (continuous infusion), SC MonitoringMonitoring: aPTT (25-40 s), : aPTT (25-40 s),
platelets, s/sxs of hemorrhageplatelets, s/sxs of hemorrhage Adverse EffectsAdverse Effects::
– HemorrhageHemorrhage– AnaphylaxisAnaphylaxis– Thrombocytopenia (HIT)Thrombocytopenia (HIT)
Low-Molecular-Weight Low-Molecular-Weight HeparinsHeparins
ExampleExample: Enoxaparin (Lovenox®): Enoxaparin (Lovenox®) MOAMOA: Enhances inhibitory effect of : Enhances inhibitory effect of
antithrombin III (inhibits factor Xa)antithrombin III (inhibits factor Xa) RouteRoute: SC: SC MonitoringMonitoring: Anti-factor Xa, SCr, : Anti-factor Xa, SCr,
plateletsplatelets Adverse EffectsAdverse Effects::
– HemorrhageHemorrhage– ThrombocytopeniaThrombocytopenia– Hypersensitivity (anaphylaxis)Hypersensitivity (anaphylaxis)
Vitamin K-Dependant Clotting Vitamin K-Dependant Clotting Factor InhibitorsFactor Inhibitors
ExampleExample: Warfarin (Coumadin®): Warfarin (Coumadin®) MOAMOA: Inhibits enzymes responsible : Inhibits enzymes responsible
for cyclic conversion of Vitamin Kfor cyclic conversion of Vitamin K RouteRoute: PO: PO MonitoringMonitoring: PT/INR (12-15 / 2-3.5), : PT/INR (12-15 / 2-3.5),
s/sxs of hemorrhage s/sxs of hemorrhage Adverse EffectsAdverse Effects::
– HemorrhageHemorrhage– AnemiaAnemia– BruisingBruising
Direct Thrombin InhibitorsDirect Thrombin Inhibitors
ExamplesExamples: : Argatroban Argatroban (Novastan®)(Novastan®) Bivalirudin (Angiomax®)Bivalirudin (Angiomax®)
MOAMOA: Directly inhibit thrombin : Directly inhibit thrombin (preventing formation of fibrin clots)(preventing formation of fibrin clots)
ArgatrobanBivalirudin
(Factor Xa)
Direct Thrombin InhibitorsDirect Thrombin Inhibitors
ExamplesExamples: : Argatroban Argatroban (Novastan®)(Novastan®) Bivalirudin (Angiomax®)Bivalirudin (Angiomax®)
MOAMOA: Directly inhibit thrombin : Directly inhibit thrombin (preventing formation of fibrin clots)(preventing formation of fibrin clots)
RouteRoute: IV: IV MonitoringMonitoring: aPTT (25-40 s): aPTT (25-40 s) Adverse EffectsAdverse Effects::
– Serious internal hemorrhageSerious internal hemorrhage– Back pain (bivalirudin)Back pain (bivalirudin)
Nursing ConsiderationsNursing Considerations
Medication SafetyMedication Safety Assess patients for signs of bleedingAssess patients for signs of bleeding
– BruisingBruising– Obvious signs of bleeding (nosebleeds, Obvious signs of bleeding (nosebleeds,
bleeding from rectum, blood in emesis)bleeding from rectum, blood in emesis)– ““Coffee Ground” or black, tarry stools / Coffee Ground” or black, tarry stools /
emesisemesis Patient educationPatient education ToxicityToxicity: warfarin – vit K : warfarin – vit K
administrationadministration heparin – protamine sulfate heparin – protamine sulfate
Patient CasePatient Case
JR is 55 YOWM recently diagnosed JR is 55 YOWM recently diagnosed with a DVT and is currently receiving with a DVT and is currently receiving enoxaparin (Lovenox).enoxaparin (Lovenox).
Before he can be d/c’ed from the Before he can be d/c’ed from the hospital, his MD wants to starts him hospital, his MD wants to starts him on chronic anticoagulation to prevent on chronic anticoagulation to prevent future DVTsfuture DVTs
Inhibition of Platelet Inhibition of Platelet FunctionFunction
(Antiplatelets)(Antiplatelets)
GP IIb/IIIa AntagonistsGP IIb/IIIa Antagonists
ExampleExample: Abciximab (ReoPro®): Abciximab (ReoPro®) MOAMOA: Inhibit GP IIb/IIIa, enzyme : Inhibit GP IIb/IIIa, enzyme
necessary for platelet aggregationnecessary for platelet aggregation
GP IIb/IIIa AntagonistsGP IIb/IIIa Antagonists
ExampleExample: Abciximab (ReoPro®): Abciximab (ReoPro®) MOAMOA: Inhibit GP IIb/IIIa, enzyme : Inhibit GP IIb/IIIa, enzyme
necessary for platelet aggregationnecessary for platelet aggregation RouteRoute: IV: IV MonitoringMonitoring: Platelets: Platelets Adverse EffectsAdverse Effects::
– HemorrhageHemorrhage– ThrombocytopeniaThrombocytopenia
Aspirin (Ecotrin®)Aspirin (Ecotrin®)
ExampleExample: Aspirin (Ecotrin®): Aspirin (Ecotrin®) MOAMOA: Irreversibly binds to COX, : Irreversibly binds to COX,
inhibiting formation of thromboxane inhibiting formation of thromboxane A2A2
Aspirin (Ecotrin®)Aspirin (Ecotrin®)
ExampleExample: Aspirin (Ecotrin®): Aspirin (Ecotrin®) MOAMOA: Irreversibly binds to COX, : Irreversibly binds to COX,
inhibiting formation of thromboxane inhibiting formation of thromboxane A2A2
RouteRoute: PO: PO MonitoringMonitoring: S/sxs hemorrhage: S/sxs hemorrhage Adverse EffectsAdverse Effects::
– Increased clotting timesIncreased clotting times– GI bleedingGI bleeding– AnaphylaxisAnaphylaxis
ADP Receptor BlockersADP Receptor Blockers
ExampleExample: Clopidogrel (Plavix®): Clopidogrel (Plavix®) MOAMOA: ADP-receptor blockers: ADP-receptor blockers
ADP Receptor BlockersADP Receptor Blockers
ExampleExample: Clopidogrel (Plavix®): Clopidogrel (Plavix®) MOAMOA: ADP-receptor blockers: ADP-receptor blockers RouteRoute: IV (loading dose), PO: IV (loading dose), PO MonitoringMonitoring: S/sxs hemorrhage: S/sxs hemorrhage Adverse EffectsAdverse Effects::
– Increased clotting timeIncreased clotting time– GI bleedingGI bleeding– Blood dyscrasias (TTP)Blood dyscrasias (TTP)
Agents for Intermittent Agents for Intermittent ClaudicationClaudication
ExampleExample: Cilostazole (Pletal®): Cilostazole (Pletal®) MOAMOA: PDE-3 inhibitor: PDE-3 inhibitor RouteRoute: PO: PO MonitoringMonitoring: S/sxs hemorrhage, : S/sxs hemorrhage,
heartheart Adverse EffectsAdverse Effects::
– Palpitation, tachycardia,Palpitation, tachycardia,– Nausea, vomittingNausea, vomitting
Nursing ConsiderationsNursing Considerations
Careful monitoring of patient Careful monitoring of patient condition (increased risk of bleeding)condition (increased risk of bleeding)
Combination with anticoagulants – Combination with anticoagulants – increased risk of bleedingincreased risk of bleeding
Injection / venipuncture sites will Injection / venipuncture sites will require prolonged pressure to control require prolonged pressure to control bleedingbleeding
Patient educationPatient education
Pharmacotherapy Pharmacotherapy with Thrombolyticswith Thrombolytics
ThrombolyticsThrombolytics
ExampleExample: Alteplase (Activase®, : Alteplase (Activase®, TPA)TPA)
MOAMOA: Fibrin-enhanced conversion of : Fibrin-enhanced conversion of plasminogen to plasmin plasminogen to plasmin
ThrombolyticsThrombolytics
ExampleExample: Alteplase (Activase®, TPA): Alteplase (Activase®, TPA) MOAMOA: Fibrin-enhanced conversion of : Fibrin-enhanced conversion of
plasminogen to plasmin plasminogen to plasmin RouteRoute: IV: IV MonitoringMonitoring: S/sxs hemorrhage, : S/sxs hemorrhage,
coagulation tests, H/H, platelets, coagulation tests, H/H, platelets, mental status, dysrhythmias (MI)mental status, dysrhythmias (MI)
Adverse EffectsAdverse Effects::– Serious internal bleedingSerious internal bleeding– Intracranial hemorrhageIntracranial hemorrhage
Nursing ConsiderationsNursing Considerations
Identify underlying conditions that Identify underlying conditions that exclude patient from receiving exclude patient from receiving thrombolyticsthrombolytics– Recent trauma, surgery, or biopsyRecent trauma, surgery, or biopsy– Arterial emboliArterial emboli– Recent cerebral embolismRecent cerebral embolism– HemorrhageHemorrhage– ThrombocytopeniaThrombocytopenia– Childbirth (within 10 days)Childbirth (within 10 days)
Pharmacotherapy Pharmacotherapy with Hemostaticswith Hemostatics
HemostaticsHemostatics
ExampleExample: Aprotinin (Trasylol®): Aprotinin (Trasylol®) MOAMOA: Inhibits fibrinolysis (affects : Inhibits fibrinolysis (affects
multiple mediators)multiple mediators)
HemostaticsHemostatics
ExampleExample: Aprotinin (Trasylol®): Aprotinin (Trasylol®) MOAMOA: Inhibits fibrinolysis (affects : Inhibits fibrinolysis (affects
multiple mediators)multiple mediators) RouteRoute: IV: IV MonitoringMonitoring: Clotting, peripheral : Clotting, peripheral
pulses, paresthesias, (+) pulses, paresthesias, (+) HomansHomans’ sign ’ sign
Adverse EffectsAdverse Effects::– ClottingClotting– ExtravasationExtravasation
QuestionsQuestions
SummarySummary
Hemostasis protects the body from Hemostasis protects the body from injuryinjury
Several pathologies may affect Several pathologies may affect hemostasishemostasis
Four main drug categories are used to Four main drug categories are used to treat coagulation disorderstreat coagulation disorders
Nurses play an important roleNurses play an important role– Monitoring drug efficacyMonitoring drug efficacy– Monitoring patient for adverse effectsMonitoring patient for adverse effects
Drugs for Drugs for Coagulation Coagulation DisordersDisorders
Andrew N. Schmelz, PharmDAndrew N. Schmelz, PharmDPost-Doctoral Teaching FellowPost-Doctoral Teaching Fellow
Purdue UniversityPurdue UniversityOctober 8, 2008October 8, 2008
[email protected]@purdue.edu