Hematology Drugs Flashcards
Mechanism of heparin
activator of antithrombin
decreases thrombin and factor Xa
short half-life
Use of heparin
immediate anticogaulation for PE
acute coronary syndrome
MI
deep venous thrombosis (DVT)
Can heparin be used during pregnancy?
YES
Which will change with heparin use, PT or PTT?
PTT needs to be monitored
Toxicity of heparin
bleeding
thrombocytopenia (HIT)
osteoporosis
drug-drug interactions
What is the heparin antidote?
protamine sulfate that has + charge that will bind - charged heparin
What are the low molecular weight heparins?
enoxaparin, dalteparin, and fondaparinux
Benefit of LMWH?
act more on factor Xa have better bioavailability 2-4 times longer half-life can be administered subQ need less laboratory monitoring NOT easily reversible
What is HIT?
heparin induced thrombocytopenia
What is the mechanism of HIT?
development of IgG antibodies against heparin-bound platelet factor 4 (PF4)
antibody-heparin-PF4 complex activates platelets –> thrombosis and thrombocytopenia
Mechanism of argatroban, bivalirudin and dabigatran?
inhibit thrombin directly
Use of argatroban, bivalirudin and dabigatran?
alternative to heparin for anticoagulating patients with HIT
Mechanism of warfarin
interferes with gamma-carboxylation of vitamin K-dependent clotting factors and protein C and S by blocking vitamin K epoxide reductase
What are the vitamin K dependent clotting factors?
II, VII, IX, X (plus protein C and S inhibited)
Can have polymorphism to warfarin response?
YES via the VKORC1 gene which is K epoxide reductase complex
Labs to monitor warfarin use?
extrinsic pathway so monitor PT (sooner) and INR
also affects intrinsic and PTT
Use of warfarin
chronic anticoagulation
Can you use warfarin in pregnant women?
NO - crosses the placenta
Toxicity of warfarin
bleeding, teratogenic, skin/tissue necrosis (believed to be due to small vessel microthromboses), drug-drug interactions
Warfarin and protein C and S
protein C and S have shorter half-lives than clotting factors II, VII, IX, X resulting in early transient hypercoagulability with warfarin use
Antidote to warfarin overdose? rapid reversal?
vitamin K; fresh frozen plasma
what is Heparin “bridging”?
heparin frequently used when starting warfarin because it only inhibits the new production of clotting factors not those that already exist
initial heparin with warfarin decreases risk of recurrent venous thromboembolism and skin/tissue necrosis
Name the direct factor Xa inhibitors
apixaban and rivaroxaban
Mech of the direct Xa inhibitors
bind to and directly inhibit factor Xa
Use of direct Xa inhibitors
tx and prophylaxis for DVT and PE (rivaroxiban)
stroke prophylaxis in patients with atrial fibrillation
Do you need to monitor labs with direct Xa inhibitors?
not usually because oral agents don’t require coagulation monitoring
Toxicity of direct Xa inhibitors
bleeding (no reversal agent available)
Name the thrombolytics
alteplase, reteplase, streptokinase, tenecteplase
Mechanism of thrombolytics
directly or indirectly aid in conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots
Lab changes with thrombolytics
increased PT and PTT, no change in platelet count
Use of thrombolytics
early MI (within first 6 hrs)
early sichemic stroke
direct thrombolysis of severe PE
Toxicity of thrombolytics
bleeding
Contraindication of thrombolytics
in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension
Antidote to thrombolytics
aminocaproic acid, an inhibitor of fibrinolysis
fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies
Mechanism of aspirin
irreversibly inhibits COX1 and COX2 enzyme by covalent acetylation
platelets cannot synthesize new enzyme, so effect lasts until new platelets are produced
Lab changes with aspirin
increased bleeding time
decreased TXA2 and prostaglandins
no effect on PT or PTT
Use of aspirin
antipyrectic, analgesic, anti-inflammatory, antiplatelet (decrease aggregation)
Toxicity of aspirin
gastric ulceration, tinnitus (CN VIII)
chronic: acute renal failure, intersitial nephritis, upper GI bleeding
What is Reye syndrome?
precipitated by aspirin use in children with viral infection
Overdose of aspirin presentation?
early presents with hyperventilation and respiratory alkalosis but transitions to mixed metabolic acidosis-respiratory alkalosis
Name the ADP receptor inhibitors
clopidogrel, prasugrel, ticagrelor (reversible), ticlodipine
Mechanism of ADP receptor inhibitors
inhibit platelet aggregation by irreversibly blocking ADP receptors
prevent expression of glycoproteins IIb/IIIa on platelet surface and prevents platelet-platelet interactions
Use of ADP receptor inhibitors
acute coronary syndrome
coronary stenting
decreased incidence or recurrence of thrombotic stroke
Toxicity of ADP receptor inhibitors
Specifically ticlodipine? Presentation?
neutropenia (ticlodipine) - presents with fever and mouth ulcers
TTP may be seen
Name the 2 phosphodiesterase III inhibitors
cilostazol, dipyridamole
Mech of PDE 3 inhibitors
inhibit enzyme leading to increase cAMP in platelets resulting in inhibition of platelet aggregation
VASODILATION as well
Use of PDE 3 inhibitors
intermitten claudication
coronary vasodilation
prevention of stroke or TIAs (combined with aspirin)
angina prophylaxis
Toxicity of PDE 3 inhibitors
nasuea, headache, facial flushing, hypotension, abdominal pain
Name the GP IIb/IIIa inhibitors
abciximab, eptifibatide, tirofiban
Mechanism of GP IIb/IIIa inhibitors
bind to glycoprotein receptor IIb/IIIa on activated platelets and prevent aggregation
Use of GP IIb/IIIa inhibitors
unstable angina
percutaneous transluminal coronary angioplasty (PCI)
Toxicity of GP IIb/IIIa inhibitors
bleeding
thrombocytopenia
