Cardio - Anticoagulants Flashcards
What is the mechanism of Warfarin?
inhibits vitK epoxide reductase
-> inhibits carboxylation of coagulation factors 10,9,7,2 (1972), and protein C and S
What are the uses of Warfarin?
Prophylaxis: DVT/PE after gyn/ortho surgery after MI with prostethic valves or chronic atrial fibrilation
How is the absoprtion and metabolism of Warfarin?
Good oral absorption - 100% (less with food)
Distribution like albumin
inactivated by CYP2C9 (beware of genetic variabillity)
Narrow therapeutic index
Slow onset of action!( Pro-coagulant at first due to lower half-life of proteins S/C)
What is the antidote for Warfarin overdose?
vit K1 (Phytonadione), or fresh frozen plasma (faster)
What are the adverse effects of Warfarin?(5)
Bleeding skin necrosis purple toe syndrome osteoporosis Teratogenicity!
How is the effect of warfarin measured?
INR ( PT ) - should be 2-3 for most indications
What is the mechanism of:
- Lepirudin, Desirubin, Bivalirudin
- Argatroban, Dabigatran
Direct thrombin inhibitors
- inhibits both soluble and and clot bound thrombin
- based on proteins from the medicinal leech
What are the uses and benefits of:
- Lepirudin, Desirubin, Bivalirudin
- Argatroban, Dabigatran
Alternatives to heparin in patients with heparin induced thrombocytopenia
- predictable anticoagulant response
- measured by aPTT
What is the mechanism and breakdown of:
Rivaroxaban
Apixaban
Edoxaban
Direct oral factor Xa inhibitors (both free and bound Xa)
P450 dependent and independent breakdown
What are the clinical uses of:
Rivaroxaban
Apixaban
Edoxaban
Rivaroxaban - prev./treat DVT after hip or knee surgery
Apixaban, Rivaroxaban - stroke prev. in atrial fibrilation
What is the mechanism of:
Enoxaparin, Dalteparin, Tinzaparin
LMWH:
Binds antithrombin III - > inactivation of Xa
What is the mechanism of unfractioned Heparin?
Binds antithrombin III -> inactivates Xa and Thrombin (II)
- immideate action
What is the mechanism of Fondaparineux?
Binds antithrombin III - > inactivation of Xa
it is the biologically active pentasaccharide in heparins
How is the effect of Heparins measured?
aPTT only for unfractioned heparin!
What is the benefit with LMWH or Fondaparineux over unfractioned heparin?(3)
Longer duration of action
More predictable
Less chance for heparin induced thrombocytopenia
less osteporosis chance?
What are the clinical uses of heparins?(5)
Rapid need of anticoagulation DVT/PE acute MI used in angioplasty with IIb/IIIa inhibitors DOC in pregnancy
What is the use of Protamine?
Antidote for heparins (except Fondaparineux)
What is the mechanism of Aspirin?
What is the anticoagulant dose per day?
irreversible inhibition of COX 1 and 2 -> less TXA2
Dose: 50 - 325 mg/d
OBS: Ibuprofen can obstruct aspirin’s binding to COX
What is the mechanism of: Ticlopidine Clopidogrel Prasugrel Ticagrelor
P2Y12 ADP receptor antagonists -> less Ca - > less GP IIb/IIIa expression
All are prodrugs activated by CYP2C9/19 except Ticagrelor
Ticlopidine: Risk of life threatning hematological reactions
What is the mechanism of:
Abciximab
Eptifibatide
Tirofiban
Inhibition of GPIIb/IIa
-> blocks fibrinogen/VWF binding -> less aggregation
What is the mechanism of:
Dipyridamole
Cilostazol
How is Cilostazol metabolized?
inhibits PDE3 -> cAMP increase - > less TXA2
- less aggregation, vasodilation
Cilostazol also lowers TGs, incresase HDL, and is metabolized by CYP3A4 ,2C19, 1A2
What are the adverse effects(2) of:
Dipyridamole
Cilostazol
Vasodilation:
coronary steal phenomenon
increased mortality in HF
Headache
What are the uses of:
Dipyridamole
Cilostazol
stroke prevention
reduce symptoms in intermittent claudication
What is the mechanism of: Alteplase Reteplase Tenecteplase (streptokinase) Urokinase (produced by kidneys)
Thrombolytics:
converts plasminogen to plasmin, which degrades fibrin
