Pharm of Anticoagulation Therapy (complete) Flashcards

1
Q

Describe the MOA of heparin

A
  • 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
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2
Q

Describe the pharmacokinetics of heparin

A

A: IV or SubQ, poor GI absorption

  • Short t1/2 (poor bioavailability)
  • Unpredictable dose response
  • Requires hospital admission/monitoring
  • Does NOT cross the placenta
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3
Q

Describe the MOA of low molecular weight heparin (LMWH)

A
  • 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
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4
Q

Describe the pharmacokinetics of LMWH

A

A: SubQ

  • Better bioavailability than heparin
  • More predictable dose response
  • Longer t1/2
  • Less monitoring (out-patient)
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5
Q

What are the differences in management of patients on heparin and LMWH?

A
  • 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)

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6
Q

What are the complications associated with heparin therapy?

A

1) Bleeding
2) Heparin-induced thrombocytopenia syndrome (HIT)
3) Allergic events

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7
Q

Describe bleeding as a complication associated with heparin therapy

A
  • Must discontinue drug w/ hemorrhage

- Effects are reversed w/ protamine sulfate

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8
Q

Describe Heparin-induced thrombocytopenia syndrome (HIT) as a complication associated with heparin therapy

A
  • 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
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9
Q

Describe allergic events as a complication associated with heparin therapy

A
  • Due to contaminant: oversulfated chondroitin sulfate

- Activation of contact system (bradykinin, complement)

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10
Q

What are alternative anticoagulant therapies used for pts with HIT?

A

1) argatroban (novastan)

2) lepirudin (refludan)

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11
Q

Describe argatroban (novastan)

A
  • an alternative therapy for pts w/ HIT

- a small molecule inhibitor

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12
Q

Describe lepirudin (refludan)

A
  • an alternative therapy for pts w/ HIT

- recombinant form of hirudin (an anticoagulant from leeches)

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13
Q

Describe the MOA of oral anticoagulant warfarin

A
  • Depletes vitamin K through inhibition of Vit K reductase
  • W/depletion => no gamma-carboxylase => no modification of coag factors
  • Ultimately depletion of coag factors
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14
Q

Describe the pharmacokinetics of warfarin

A
  • 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

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15
Q

What are the uses of warfarin?

A
  • Venous thromboembolism (w/heparin)
  • Embolism in pts w/ prosthetic valves or atrial fibrillation
  • Stroke, recurrent infarctions
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16
Q

What are the adverse rxns and potential complications associated with warfarin use?

A
  • Hemorrhage (requires vitK admin or plasma transfusion)
  • Cross placenta
  • Drug interactions
  • Delayed action onset
  • Requires monitoring
17
Q

Describe the MOA of fibrinolytic agents

A
  • Lyse clots already formed
  • Instead of preventing clot formation
  • Increases activation of plasmin from plasminogen => then fibrin is broken down more quickly

CLOT BUSTERS!

18
Q

What are the uses of fibrinolytic agents?

A
  • Acute MI (emergency tx — must be used w/in 3 hrs)
  • Ischemic stroke
  • DVT and PE
19
Q

Describe the MOA of antiplatelet agents

A
  • 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

20
Q

What are the uses of antiplatelet agents?

A

Aspirin:

  • After acute MI
  • Thrombotic stroke (w/ thrombolytics)

ADP blockers:
-same

GP inhibitors:

  • Tx of AMI
  • Unstable angina
  • before, during, after angioplasty
21
Q

What are the uses of heparin?

A
  • 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
22
Q

What are types of fibrinolytic agents?

A
  • T-PA
  • Urokinase
  • Streptokinase