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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
Why is INR better for monitoring warfarin than prothrombin time?
It standardises the values between labs by taking different lab thromboplastins into account
26
Do the majority of drugs that interact with warfarin potentiate it or inhibit it?
Most potentiate it i.e. increase anticoagulant effect
27
Give some examples of drugs that will potentiate the effect of warfarin if started de novo.
- Amiodarone - Quinolones - Metronidazole - Cimetidine - Alcohol - Aspirin - Cephalosporins - NSAIDs (displacement from albumin)
28
Give some examples of drugs that will inhibit the effect of warfarin if started de novo.
- Antiepileptics - St Johns Wart - Rifampicin
29
Other than the teratogenic effect, what is the main ADR of warfarin?
Bleeding + Bruising
30
Where do pts on warfarin commonly bleed from?
Nose Injection sites GI tract Intracranial blood vessels
31
What does a high INR increase risk of?
Bleeding
32
How can warfarin be reversed?
Stop the warfarin!! | Parenteral Vitamin K or FFP
33
Does vitamin K work fast or slow to reverse the effect of warfarin?
Slowly
34
Does FFP work fast or slow to reverse the effect of warfarin?
Fast
35
When can FFP be given to reverse the effect of warfarin?
If the pt has severe/serious bleeding - it isn't used very often.
36
When should INR be checked during the day?
Between 9am and 11am.
37
How often should INR be checked?
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
What time of day is warfarin recommended to be taken at?
6pm - but the pt should aim to take it at the same time of day each day at the very least.
39
What do the different doses of warfarin tablets look like?
``` 0.5mg = white 1mg = brown 3mg = blue 5mg = pink ```
40
What is the recommendation for a missed dose of warfarin?
Take it as soon as you remember unless its the next day, in which case just skip the missed dose.
41
If a drug is started that might affect INR, when should INR be checked?
4-5 days after starting the new drug.
42
Other than warfarin, what is the other major group of anticoagulants?
Heparins
43
How do heparins work?
Activates anti-thrombin III, and deactivates factors: - Xa - IIa - IXa i.e. inhibits the activated clotting factors
44
What are the 2 forms of heparin available?
- Unfractionated | - Low molecular weight
45
How is unfractionated heparin given?
IV usually but can be given SC
46
How is LMWH given?
SC
47
What does unfractionated heparin mean?
It is a mixture of different legths of heparin chains (12-15 kDaltons)
48
Why is unfractionated heparin better at inactivating thrombin than LMWH?
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
Why is LMWH preferred to unfractionated heparin?
- It is absorbed more uniformly - High bioavailability (90%) - Dose response is more predictable - Monitoring not required usually
50
Give example of factor Xa inhibitors used to anticoagulate patients commonly.
Fondaparinux Rivaroxaban Apixaban Edoxaban
51
Give example of direct thrombin inhibitors used to anticoagulate patients commonly.
Dabigatran
52
Why do heparins need to be given parenterally?
They are poorly absorbed from GI tract
53
How should unfractionated heparin be initiated?
Bolus the IV infusion
54
How should LMWH be initiated?
OD/BD S/C injection
55
When is LMWH used to prevent VTE?
Peri-operatively or in immbolity
56
When is LMWH used as a treatment (rather than prophylaxis)?
DVT/PE AF ACS Pregnancy (instead of warfarin)
57
What are the major ADRs associated with heparin?
- Bruising/bleeding - Thrombocytopenia - Osteoporosis
58
Why does thrombocytopenia occur in some individuals following heparin therapy?
As an autoimmune response - immunogenic nature causes immune complexes to activate more platelets and deplete stores.
59
How can heparin therapy be reversed?
Stop the heparin Give protamine if actively bleeding
60
What needs to be monitored when a pt starts unfractionated heparin?
APTT
61
What needs to be monitored when a pt starts LMW heparin?
Nothing!! NB some people may need the odd Xa assay.
62
List the commonly used anti-platelets.
Aspirin Dipyridamole Clopidogrel Glycoprotein IIb/IIIa inhibitors
63
How does aspirin work?
COX-1 inhibition (irreversible)
64
How does Dipyridamole work?
Phosphodiesterase inhibition
65
How do glycoprotein IIb/IIIa inhibitors work?
As the name suggests to decrease platelet crosslinking by fibrinogen

Clinical Pharmacology and Therapeutics (26 decks)

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