Pharm of Anticoagulation Therapy (complete) Flashcards
Describe the MOA of heparin
- proteoglycan w/sulfated polysaccharide — varying lengths
- Binds to anti-thrombin III => leads to increased protease inactivation (especially thrombin and 10a)
- Also inactivates 9a, 12a
- Heparin increases rate of thrombin inactivation by 1000x
- prevents fibrin formation
Describe the pharmacokinetics of heparin
A: IV or SubQ, poor GI absorption
- Short t1/2 (poor bioavailability)
- Unpredictable dose response
- Requires hospital admission/monitoring
- Does NOT cross the placenta
Describe the MOA of low molecular weight heparin (LMWH)
- A smaller version of heparin
- Bind to anti-thrombin III but not thrombin
- Does not inhibit thrombin by anti-thrombin
- Does selectively bind to and inactivates 10a
Describe the pharmacokinetics of LMWH
A: SubQ
- Better bioavailability than heparin
- More predictable dose response
- Longer t1/2
- Less monitoring (out-patient)
What are the differences in management of patients on heparin and LMWH?
- You need to be admitted into the hospital if given heparin
- requires lots of monitoring due to unpredictability of dose response
Not the case with LMWH (can do outpatient)
What are the complications associated with heparin therapy?
1) Bleeding
2) Heparin-induced thrombocytopenia syndrome (HIT)
3) Allergic events
Describe bleeding as a complication associated with heparin therapy
- Must discontinue drug w/ hemorrhage
- Effects are reversed w/ protamine sulfate
Describe Heparin-induced thrombocytopenia syndrome (HIT) as a complication associated with heparin therapy
- There’s a low platelet count b/c of production of Abs to platelet factor 4/heparin complexes => Abs bind to platelets => pro-thrombic state
- Less common w/ LMWH and fondaparinux
Describe allergic events as a complication associated with heparin therapy
- Due to contaminant: oversulfated chondroitin sulfate
- Activation of contact system (bradykinin, complement)
What are alternative anticoagulant therapies used for pts with HIT?
1) argatroban (novastan)
2) lepirudin (refludan)
Describe argatroban (novastan)
- an alternative therapy for pts w/ HIT
- a small molecule inhibitor
Describe lepirudin (refludan)
- an alternative therapy for pts w/ HIT
- recombinant form of hirudin (an anticoagulant from leeches)
Describe the MOA of oral anticoagulant warfarin
- Depletes vitamin K through inhibition of Vit K reductase
- W/depletion => no gamma-carboxylase => no modification of coag factors
- Ultimately depletion of coag factors
Describe the pharmacokinetics of warfarin
- Rapidly absorbed
- Good bioavailability
- Long t1/2
- Slow action onset
Effective dose = 3-5 days => b/c you can’t get rid of all coag factors at once, still have some there
What are the uses of warfarin?
- Venous thromboembolism (w/heparin)
- Embolism in pts w/ prosthetic valves or atrial fibrillation
- Stroke, recurrent infarctions
What are the adverse rxns and potential complications associated with warfarin use?
- Hemorrhage (requires vitK admin or plasma transfusion)
- Cross placenta
- Drug interactions
- Delayed action onset
- Requires monitoring
Describe the MOA of fibrinolytic agents
- Lyse clots already formed
- Instead of preventing clot formation
- Increases activation of plasmin from plasminogen => then fibrin is broken down more quickly
CLOT BUSTERS!
What are the uses of fibrinolytic agents?
- Acute MI (emergency tx — must be used w/in 3 hrs)
- Ischemic stroke
- DVT and PE
Describe the MOA of antiplatelet agents
- Inhibit platelet formation and aggregation
Three ways:
1) Inhibits thromboxane A2 production => irreversibly inactivates COX1
2) ADP receptor blockers (irreversibly) => prevents alpha granule secretion
3) GP2a/3a inhibitors => block binding of fibrinogen to GPs
What are the uses of antiplatelet agents?
Aspirin:
- After acute MI
- Thrombotic stroke (w/ thrombolytics)
ADP blockers:
-same
GP inhibitors:
- Tx of AMI
- Unstable angina
- before, during, after angioplasty
What are the uses of heparin?
- Venous thrombosis (w/warfarin)
- PE (w/warfarin)
- Management of unstable angina, MI (w/fibrinolytics)
- Coronary angioplasty, stent placement
- Surgery that require cardiopulm bypass
- Kidney dialysis
What are types of fibrinolytic agents?
- T-PA
- Urokinase
- Streptokinase
