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Clinical Pharmacology and Therapeutics > Anticoagulant and Antiplatelet Therapy > Flashcards

Anticoagulant and Antiplatelet Therapy Flashcards

1
Q

What are the principles of managing an arterial clot?

A

Antiplatelets and thrombolysis

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2
Q

What are the principles of managing an venous clot?

A

Anti-coagulation

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3
Q

What factors lead to increased risk of arterial thrombosis/embolisation?

A

Endothelial damage
Cardiac abnormalities
Hypercoagulability

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4
Q

What factors lead to increased risk of venous thrombosis/embolisation?

A

Immobility

Hypercoagulability

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5
Q

What are the 2 elements of the clotting pathway?

A

Intrinsic and extrinsic pathways

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6
Q

What is the basic mechanism of action of warfarin?

A

Inhibits the production of active/functional vitamin K dependant clotting factors

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7
Q

Which clotting factors are vitamin K dependant?

A

II (Prothrombin)
VII
IX
X

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8
Q

Considering it’s mechanism of action, which pathway in clotting does warfarin inhibit?

A

Extrinsic i.e. it inhibits the precursors in the clotting cascade

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9
Q

Is the onset of action of warfarin fast or slow?

A

Slow - takes many days due to the slow turnover of clotting factors

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10
Q

How is warfarin given?

A

PO

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11
Q

Why is it possible to give warfarin PO?

A

It has good GI absorption

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12
Q

Why is the slow onset of warfarin important to recognise?

A

The period between starting treatment and the onset of benefit needs to be covered by heparinisation

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13
Q

What is the half life of warfarin?

A

Around 48 hours, but it can be unpredictable

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14
Q

Why is the long half life of warfarin important to know about clinically?

A

It means that pre-operatively, warfarin needs to be stopped for 3-5 days for new clotting factors to be synthesised and INR to become <1.5

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15
Q

What is the target INR for patients on warfarin?

A

Depends on the indication:

  • 2.5 for DVT/PE/AF/cardiomyopathy/mitral valve pathology/Prosthetic valves/MI
  • 3.5 for recurrent DVT/PEs

Mechanical heart valves - depends on the inidividual

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16
Q

How long is warfarin given for isolated calf vein DVT?

A

6 weeks

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17
Q

How long is warfarin given for VTE following surgery/other transient risk factors?

A

3 months

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18
Q

How long is warfarin given for unprovoked proximal DVT or PE?

A

At least 3 months

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19
Q

How does warfarin circulate?

A

Heavily protein bound

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20
Q

Why does the protein binding of warfarin matter?

A

Caution needs to be exercised with drugs that might displace it

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21
Q

How is warfarin metabolised?

A

CYP450 liver enzyme

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22
Q

When does a pt on warfarin need to be careful wrt warfarin metabolism?

A

If they have liver disease or are taking drugs that affect cyp450 system

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23
Q

Is warfarin teratogenic?

A

Yes, especially in the 1st trimester.

In the 3rd trimester it can cause brain haemorrhage

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24
Q

How is warfarin monitored?

A

International Normalised Ratio

Prothrombin Time can also be used

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25
Q

Why is INR better for monitoring warfarin than prothrombin time?

A

It standardises the values between labs by taking different lab thromboplastins into account

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26
Q

Do the majority of drugs that interact with warfarin potentiate it or inhibit it?

A

Most potentiate it i.e. increase anticoagulant effect

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27
Q

Give some examples of drugs that will potentiate the effect of warfarin if started de novo.

A
  • Amiodarone
  • Quinolones
  • Metronidazole
  • Cimetidine
  • Alcohol
  • Aspirin
  • Cephalosporins
  • NSAIDs (displacement from albumin)
28
Q

Give some examples of drugs that will inhibit the effect of warfarin if started de novo.

A
  • Antiepileptics
  • St Johns Wart
  • Rifampicin
29
Q

Other than the teratogenic effect, what is the main ADR of warfarin?

A

Bleeding + Bruising

30
Q

Where do pts on warfarin commonly bleed from?

A

Nose
Injection sites
GI tract
Intracranial blood vessels

31
Q

What does a high INR increase risk of?

A

Bleeding

32
Q

How can warfarin be reversed?

A

Stop the warfarin!!

Parenteral Vitamin K or FFP

33
Q

Does vitamin K work fast or slow to reverse the effect of warfarin?

A

Slowly

34
Q

Does FFP work fast or slow to reverse the effect of warfarin?

A

Fast

35
Q

When can FFP be given to reverse the effect of warfarin?

A

If the pt has severe/serious bleeding - it isn’t used very often.

36
Q

When should INR be checked during the day?

A

Between 9am and 11am.

37
Q

How often should INR be checked?

A

Initially every day/alternate days until INR stable.

Then twice weekly for 1-2 weeks.

Every 1-12 weeks depending on the pt and stability of INR.

38
Q

What time of day is warfarin recommended to be taken at?

A

6pm - but the pt should aim to take it at the same time of day each day at the very least.

39
Q

What do the different doses of warfarin tablets look like?

A 
0.5mg = white
1mg = brown
3mg = blue
5mg = pink
40
Q

What is the recommendation for a missed dose of warfarin?

A

Take it as soon as you remember unless its the next day, in which case just skip the missed dose.

41
Q

If a drug is started that might affect INR, when should INR be checked?

A

4-5 days after starting the new drug.

42
Q

Other than warfarin, what is the other major group of anticoagulants?

A

Heparins

43
Q

How do heparins work?

A

Activates anti-thrombin III, and deactivates factors:

  • Xa
  • IIa
  • IXa

i.e. inhibits the activated clotting factors

44
Q

What are the 2 forms of heparin available?

A
  • Unfractionated

- Low molecular weight

45
Q

How is unfractionated heparin given?

A

IV usually but can be given SC

46
Q

How is LMWH given?

A

SC

47
Q

What does unfractionated heparin mean?

A

It is a mixture of different legths of heparin chains (12-15 kDaltons)

48
Q

Why is unfractionated heparin better at inactivating thrombin than LMWH?

A

It contains longer chain heparins with can bind to antithrombin III and thrombin simultaneously, where as LMWH is too short so only binds to antithrombin III

49
Q

Why is LMWH preferred to unfractionated heparin?

A
  • It is absorbed more uniformly
  • High bioavailability (90%)
  • Dose response is more predictable
  • Monitoring not required usually
50
Q

Give example of factor Xa inhibitors used to anticoagulate patients commonly.

A

Fondaparinux
Rivaroxaban
Apixaban
Edoxaban

51
Q

Give example of direct thrombin inhibitors used to anticoagulate patients commonly.

A

Dabigatran

52
Q

Why do heparins need to be given parenterally?

A

They are poorly absorbed from GI tract

53
Q

How should unfractionated heparin be initiated?

A

Bolus the IV infusion

54
Q

How should LMWH be initiated?

A

OD/BD S/C injection

55
Q

When is LMWH used to prevent VTE?

A

Peri-operatively or in immbolity

56
Q

When is LMWH used as a treatment (rather than prophylaxis)?

A

DVT/PE
AF
ACS
Pregnancy (instead of warfarin)

57
Q

What are the major ADRs associated with heparin?

A
  • Bruising/bleeding
  • Thrombocytopenia
  • Osteoporosis
58
Q

Why does thrombocytopenia occur in some individuals following heparin therapy?

A

As an autoimmune response - immunogenic nature causes immune complexes to activate more platelets and deplete stores.

59
Q

How can heparin therapy be reversed?

A

Stop the heparin

Give protamine if actively bleeding

60
Q

What needs to be monitored when a pt starts unfractionated heparin?

A

APTT

61
Q

What needs to be monitored when a pt starts LMW heparin?

A

Nothing!!

NB some people may need the odd Xa assay.

62
Q

List the commonly used anti-platelets.

A

Aspirin
Dipyridamole
Clopidogrel
Glycoprotein IIb/IIIa inhibitors

63
Q

How does aspirin work?

A

COX-1 inhibition (irreversible)

64
Q

How does Dipyridamole work?

A

Phosphodiesterase inhibition

65
Q

How do glycoprotein IIb/IIIa inhibitors work?

A

As the name suggests to decrease platelet crosslinking by fibrinogen

Clinical Pharmacology and Therapeutics (26 decks)

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