2.4 Anticoagulants Flashcards Preview

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Flashcards in 2.4 Anticoagulants Deck (30):
1

How does heparin work as an anticoagulant?

potentiates the formation of complexes between Antithrombin III and activated factors of the coagulation cascade leading to their inactivation.

2

How does antithrombin III work

It forms a 1:1 complex with activated factors (thrombin, Xa, IXa, XIIa) via a reactive site

3

How is heparin administered?

Parenteral (prophylaxis)
Iv infusion with or without bolus for therapy

4

How is heparin cleared?

Saturable: (rapid) – heparin binds to receptors on endothelial cells and macrophages and is internalized, depolymerized and metabolized into smaller fragments

Non-saturable clearance (slow): Renal

5

How do you monitor heparin therapy?

APTT - important due to the variability in protein binding and metabolism between individuals

6

What are the complications of heparin therapy?

Bleeding
Heparin induced thrombocytopenia
Osteoporosis
Transaminitis
Hyperaldosteronism
Hypersensitivity

7

What factors does warfarin inhibit?

II (thrombin)
VII
IX
X

8

How does warfarin work?

It blocks the regeneration of vitamin K which is needed for the addition of gamma-carboxyglutamine acid residues on factors II, VII, IX and X as well as protein C and Protein S

9

How does warfarin work?

It blocks the regeneration of vitamin K which is needed for the addition of gamma-carboxyglutamine acid residues on factors II, VII, IX and X as well as protein C and Protein S

10

How is warfarin metabolised and what are the effects of warfarin dependent on?

By CYP2C9

Effects are dependent on the T1/2 of the vitamin K dependent clotting factors in the blood

11

What do you need to give with warfarin?

It has a delayed onset of anticoagulation effect so commence after a patient is on heparin or LMWH

12

What will initially happen with warfarin treatment?

Initial hypercoaguable state due to the decreased level of protein C

13

What are the important drug interactions of warfarin?

Displacement of warfarin from albumin binding sites (anticonvulsants)

Inhibition or acceleration of drug clearance (antibiotics, barbituates)

Reduced absorption (cholestyramine)

14

What genetic polymorphisms affect warfarin?

CYP2C9 polymorphisms

Vitamin K epoxide reductase polymorphisms

15

How do you monitor warfarin therapy?

Prothrombin Time

16

What are the complications of warfarin therapy?

Haemorrhage
Warfarin induced skin necrosis

17

What causes warfarin induced skin necrosis?

the initial decrease in protein C which results in paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis

18

How can you reverse warfarin therapy?

Cessation - 3-5 days
Prothrombin complex concentrate
Vitamin K infusion - complete reversal with 10 mg

19

Where is the main action of LMWH?

Factor Xa

20

Where is the main action of LMWH?

Factor Xa

21

What is the advantage of LMWH?

less binding to plasma, platelet or endothelial derived proteins → more predictable response to weight adjusted dose than heparin

22

What are the complication of LMWH?

Bleeding, especially in renal impairment

Thrombocytopenia: lower incidence if initial exposure to LMWH rather than heparin

LMWH cannot be recommended once heparin associated thrombocytopenia has occurred

23

How can you reverse LMWH therapy?

50% reversal with use of protamine

24

What drug is used when there is heparin associated thrombocytopenia?

Danaparoid - similar to LMWH (blocks Xa)

25

What are the two direct thrombin inhibitros?

Hirudin and Bivalirudin

26

What drugs inhibit Xa?

Rivaroxaban and Apixaban

27

What are the two direct thrombin inhibitors?

Hirudin and Bivalirudin

28

What drugs inhibit Xa?

Rivaroxaban, Apixaban and Aristotle

29

How does Rivaroxaban and Apixaban work and what are they used for?

Inhibit Xa - works in the plasma and in the prothrombinase complex within the clot to which heparin cannot reach

used for post surgical prevention

30

What is usually used in conjunction with anticoagulants?

Antiplatelet drugs such as aspirin