Drugs Affecting Hemostasis: 2) Anticoagulants Flashcards
Anticoagulants
- Affect body’s ability to form a platelet plug
- Vitamin K antagonists
- vitamin K is needed to make clotting factors
- decreases activity of clotting factors II, VII, IX, X and protein C (endogenous anti-coagulant) and protein S
- clotting factors & bone (osteoblasts/osteoclast)
- activity sensitive to dietary vitamin K- consistent intake is essential
Warfarin (Coumadin) Rivaroxaban (Xarelto) Edoxaban (Savaysa) Apixaban (Eliquis) Fondaparinux (Arixtra) Dabigatran (Pradaxa) -idarucizumab (praxbind-antidote) Hirudin derivatives: Leprirudin, Desirudin, Bivalrudin
Anticoagulants
Warfarin (Coumadin)
General info
Oldest and most widely used
- PO
- prefects body’s recycling of Vitamin K
- works on clotting factors II and X (in normal cascade)
- paired with heparin: works immediately
Warfarin (Coumadin)
MOA
- blocks the formation of Vitamin K dependent clotting factors: II, VII, IX, X, protein C and S
- prevents bodies recycling of Vitamin K
- works on clotting factors II and X
Warfarin (Coumadin)
Monitoring information
Monitoring required -INR blood test (target 2-3) ⬆️ INR= blood is very thin ⬇️ INR= blood is thick (no warfarin present) * highly individualized * metabolism is complicated
Warfarin (Coumadin)
Risks/cautions
- high drug inx risk
- dietary restrictions: green leafy veg, livers and K supplements
- takes a long time to start dosing
- NO antidote
Warfarin (Coumadin)
Adverse effects
Bleeding
Purple toe syndrome
Skin necrosis
Osteoporosis (long term use)
To reverse the effects of warfarin if the blood is too thin?
Give vitamin K
Eat a salad
Give fresh frozen plasma
Rivaroxaban (Xarelto) Edoxaban (Savaysa) Apixaban (Eliquis) Fondaparinux (Anitra) Dabigatran (Pradaxa) Hirudin derivatives: Leprirudin, Desirudin, Bivalrudin Argatraban
2nd, 3rd line therapy options
Work right away
* cause more bleeding than warfarin
* much more predictable in effectiveness= low variability patient to patient
Rivaroxaban (Xarelto)
Specific Xa inhibitor
- PO, variable bioavailability
- some drug inx risk
- bleeding- avoid 6-8 hrs after surgery
- caution with renal dysfunction
Edoxaban ( Savaysa)
Apixaban (Eliquis)
Specific Xa inhibitors
- PO
- drug inx risks
- sensitive to renal fxn
- role in therapy uncertain
Fondaparinux (Arixtra)
Specific Xa inhibitor
- injectable
- eliminated renally
- bleeding: avoid 6-8 hrs after surgery
- caution with renal fxn
Dabigatran (Pradaxa)
Direct thrombin inhibitor
PO
* use/discard after 120 days after opening container
-sensitive to humidity: ⬇️ drug effectiveness
-given in manufacture container or blister packs
* do not crush, chew or open capsules
Dabigatran (Pradaxa)
Drug inx risk
Sensitive to renal fxn
Antidote for Dabigatran ( Pradaxa)?
Idarucizumab (praxbind)
- binds to Dabigatran in blood and inactivates it
- specific to Dabigatran
- can receive Dabigatran in 24 hrs
Hirudun derivatives: Leprirudin, Desirudin, Bivalrudin
- injectable
Direct thrombin inhibitor - irreversible IIa inhibitors
Renal elimination
Argabatran
Direct thrombin inhibitor (IIa)
* injectable
Small synthetic: can bind to IIa in clot
Hepatic metabolism
Heparin: unfractionated heparin (UFH)
MOA
Enhance the actions of antithrombin -anti Xa, IIa -unfavorable PK: variable dose-dependent absorption -onset 1-2 hrs -dose dependent t1/2: 30-90 min Renal metabolism and elimination
UFH
Molecules are all different lengths
Each size works differently: more mechanisms than LMWH
* active against clotting factor Xa and IIa (thrombin)
Heparin
Monitoring and risks
A PTT- many limitations
- anti Xa activity
- heparin concentration (0.3-0.7 units/mL)
- Bleeding: heparin induced thrombocytopenia
- osteoporosis with long term use
LMWH
Short chained- more consistent in length MOA: enhance actions of antithrombin * more predictable PK and effects -primarily renal elimination -weight based dosing( even in obese PTs) * monitoring is less necessary * lower risk of bleeding * lower variability from pt to pt
What alter UFH and LMWH variability?
Weight and renal fxn
