Antiplatelets, Anticoagulants & Thrombolysis Flashcards

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1
Q

What is the difference between a venous thrombus and an arterial thrombus.

A

Venous - ‘red’ - RBC and fibrin rich, platelet low.

Arterial - ‘white’ - platelet rich, fibrin low.

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2
Q

How does treatment differ for arterial and venous thrombosis?

A

Arterial - use antiplatelets and fibrinolytic drugs.

Venous - use anticoagulants.

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3
Q

Describe the production of prostaglandins and thromboxanes.

A

Tissue damage during the inflammatory process produces phospholipase A2, which converts phospholipids in the membrane into arachidonic acid. Oxidation of arachidonic acid by COX enzymes produces eicosanoids such as thromboxanes, prostaglandins and leukotrienes.

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4
Q

What is the rate limiting enzyme in the eicosanoid generation?

A

Phospholipase A2.

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5
Q

How is thromboxane A2 formed and what are its effects?

A

Formed by COX-1

Causes vasoconstriction and promotes platelet aggregation

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6
Q

How is PGI-2 produced and what are its effects?

A

Produced by COX-2

Causes vasodilation and inhibits platelet aggregation

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7
Q

Name 3 COX-1 selective inhibitors.

A

Aspirin
Ibuprofen
Naproxen

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8
Q

What is the MOA of COX-1 inhibitors.

A

Inhibit COX-1 enzyme, reducing TXA2 synthesis, therefore inhibits platelet aggregation.

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9
Q

What is the MOA of COX-2 inhibitors?

A

Inhibit COX-2 enzymes, reducing PGI2 synthesis, which promotes platelet aggregation.

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10
Q

Name a COX-2 selective inhibitor.

A

Celecoxib

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11
Q

Name a non-selective COX inhibitor.

A

Diclofenac

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12
Q

State a side effect of aspirin.

A

Prolonged bleeding time due to reduced TXA 2 synthesis and reduced platelet aggregation.

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13
Q

What are P2Y12 inhibitors used for? What is their MOA?

A

Antiplatelet agents

Inhibit binding of ADP to P2Y12 receptors, inhibits activation of GPIIb/IIIa receptors.

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14
Q

What drug class are clopidogrel and ticagrelor?

A

P2Y12 receptor antagonists, both are prodrugs.

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15
Q

What are Glycoprotein IIb/IIIa inhibitors used for? What is their MOA?

A

Antiplatelet agents
Antibody irreversibly blocks receptor, preventing fibrinogen binding to IIb/IIIa receptors on platelets, reduces platelet aggregation.

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16
Q

Name a GIIb/IIIa inhibitor.

A

Abciximab.

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17
Q

What drug class is dipyramidole and what is it used for?

A

Phosphodiesterase inhibitor - used as an antiplatelet.

18
Q

What is the MOA of dipyramidole?

A

Prevents cAMP and cGMP degradation, which inhibits expression of GPIIb/IIIa, reducing platelet aggregation.

19
Q

What are streptokinase, alteplase and reteplase used for? What is their MOA?

A

Fibrinolytic

Increase fibrinolysis.

20
Q

What is the MOA of tranexamic acid?

A

Anti-fibrinolytic
Inhibits fibrinolysis, slows breakdown of clots, which helps to prevent prolonged bleeding.
Often used for menorrhagia.

21
Q

What is the MOA of warfarin?

A

Stops production of active vitamin K, reducing synthesis of vitamin K-dependent clotting factors - II (prothrombin), VII, IX and X.

22
Q

What is heparin cover?

A

When warfarin is taken, there is a delay in onset of action as active circulating clotting factors will be present for several days. During this time, heparin can be given.

23
Q

Is warfarin taken orally or IV? Why?

A

Orally as it has 100% bioavailability and good GI absorption.

24
Q

How can warfarin be monitored?

A
  • INR (internal normalised ratio - ratio of speed of someone’s clotting action compared to standardised value).
  • prothrombin time
25
Q

Is warfarin safe in pregnancy?

A

No, as it can cross the placenta.

26
Q

What is the main side effect of warfarin?

A

Bleeding.

27
Q

What is the most effective antidote to bleeding caused by warfarin?

A

Vitamin K1

Also stop warfarin

28
Q

In a patient with PE, which drugs should be given?

A
  • immediate heparinisation - stops thrombus propagation
  • oral anticoagulant e.g. Warfarin or DOAC e.g. Rivaroxiban for 3 months
  • fibrinolytic e.g. Streptokinase
29
Q

In patients who cannot be given anticoagulant drugs, which surgical intervention can be used?

A

IVC filter - collects any clots coming up from the legs.

30
Q

What is a d-dimer test?

A

Positive result indicates that there has been significant thrombus formation and breakdown in the body e.g. May have had a PE. (D-diner is a fibrin degradation product released into the blood when a thrombus is degraded by fibrinolysis).

31
Q

What would happen if you gave warfarin and aspirin together?

A

Dual action of inhibiting platelet function/thinning blood can lead to bleeding.

32
Q

What is a parenteral anticoagulant?

A

Means that it doesn’t enter the GI tract e.g. Heparin, which is given IV.

33
Q

Name the 2 types of heparin that can be given.

A

Unfractionated heparin

Low molecular weight heparin

34
Q

Name some uses for heparin.

A
  • DVT
  • PE
  • AF
  • pregnancy (doesn’t cross the placenta)
35
Q

What is heparin reversal?

A

Protamine sulphate can be given as an antidote to heparin, it dissociates heparin from ATIII, often given following surgery.

36
Q

What is heparin induced thrombocytopenia (HIT)?

A

When heparin-dependent IgG antibodies activate platelets and produce a hypercoagulable state.

37
Q

What is the MOA of unfractionated heparin?

A

Binds to AIII (antithrombin), inactivating IIa and Xa. To inhibit IIa, heparin needs to simultaneously bind to ATIII and IIa (thrombin). To inhibit Xa, only needs ATIII binding.

38
Q

What is the MOA of low molecular weight heparin?

A

Binds to AIII (antithrombin) to inactivate Xa.

39
Q

Name 2 LMWHs.

A

Dalteparin

Enoxaparin

40
Q

Of UFH and LMWH, which is more likely to cause thrombocytopenia?

A

UFH

41
Q

What is the MOA of Fondaparinux?

A

Anticoagulant that selectively inhibits Xa by binding to ATIII.

42
Q

What is a DOAC?

A

Direct oral anticoagulant:
Rivaroxaban, apixaban, that inhibits both free Xa and that bound with ATIII. Has no effect on IIa.
Argatroban and dabigartran both inhibit IIa.