Anticoagulants/Antiplatelets

Question 1

Warfarin is metabolised how?

Answer 1

Hepatic metabolism- by CYP450 enzyme

Question 2

What is Warfarins distribution once absorbed?

Answer 2

Heavily protein bound to albumin 99%

Question 3

What drugs would increase the conc of warfarin in the blood? (2 mechanisms)

Answer 3

By displacing warfarin bound to albumin- NSAIDs

By inhibiting CYP450- cimetidine, amiodarone, alcohol, metronidazole

Question 4

How long is Warfarins onset of action?

Answer 4

Slow and so may need heparin to cover initially

Question 5

How fast or slow is Warfarins offset?

Answer 5

Half life ~48 hrs

Therefore need to stop 3 days prior to surgery to allow for making of new clotting factors

Question 6

Side effects of Warfarin

Answer 6

Bleeding, epistaxis, GI bleeding, intracranial

Question 7

How can you reverse warfarin?

Answer 7

Parenteral vitamin K (acts slowly)
Fresh frozen plasma (acts quickly)
Can also give Prothrombin Complex Concentrate (ii, ix, x)

Question 8

What cautions do you need to be wary of with warfarin?

Answer 8

Teratogenic in 1st trimester

Can cause brain haemorrhage in 3rd trimester

Question 9

What is INR?

Answer 9

Patients prothrombin time OVER average prothrombin time

Question 10

Which common drugs should be avoided in warfarin use?

Answer 10

Antiepileptics
St Johns Wort
Rifampicin

(All induce hepatic enzymes)

Question 11

Mechanism of action of warfarin?

Answer 11

Vitamin K antagonist.

Vitamin K is needed for the production of active factors II, VII, IX, X

Question 12

What is Virchow triad?

Answer 12

Hypercoaguability
Blood stasis
Endothelial damage

Question 13

Mechanism of action of heparin

Answer 13

Binds reversibly to anti-thrombin therefore
Almost instant inactivation of factors IIa, Xa
Therefore prevents progression of existing clots

Question 14

Name two examples of a LMWH

Answer 14

Dalteparin

Enoxaparin

Question 15

Give three advantages of LMWH over unfractionated

Answer 15

Absorbed better/better absorption predictability
Higher bioavailability (90%)
More predictable dose response curve

Question 16

Name three negatives of unfractionated heparin

Answer 16

Non linear dose response curve
Poor absorption from gut therefore needs to be IV or SC
Can’t be eliminated in haemodialysis

Question 17

Name three adverse drug reCtions of unfractionated heparin

Answer 17

Bruising/bleeding
Osteoporosis
Thrombocytopenia (immune phenomenon)

Question 18

How can you reverse heparin?

Answer 18

Stop the heparin asap

Use Protamine Sulfate (dissociates the heparin from the antithrombin)

Question 19

Name an advantage of LMWH over warfarin

Answer 19

Is safe to use in pregnancy

Question 20

Name three DOACs

Answer 20

Rivoroxaban
Apixaban
Dabigatran

Question 21

What is the mechanism of action of Rivoroxaban

Answer 21

Competitive antagonist of factor Xa

Question 22

What is the mechanism of action of Dabigatran

Answer 22

Competitive antagonist of Thrombin

Question 23

Name a positive of DOACs

Answer 23

No monitoring required
No antidote available
Have more predictable pharmacokinetics

Question 24

Name one drug you should avoid while taking Dabigatran

Answer 24

PPI

they reduce absorption

Question 25

How are DOACs excreted?

Answer 25

Renal | Therefore in renal exposure, you will get increased drug exposure

Question 26

Name three anti-platelet drugs

Answer 26

Aspirin Clopidogrel Dipyridamole

Question 27

Mechanism of action of aspirin

Answer 27

Irreversibly binds to COX enzyme COX produces pro-inflammatory prostaglandins and thromboxanes Thromboxanes facilitate platelet aggregation

Question 28

Side effects of aspirin

Answer 28

Bronchospasm GI upset Hypersensitivity reactions

Question 29

Contraindications of aspirin

Answer 29

Asthma Peptic ulcer If pt has hypersensitivity to NSAID

Question 30

Mechanism of action of clopidogrel

Answer 30

Prevents binding of ADP to platelet receptor which stops the cross linking of fibrin

Question 31

How is clopidogrel metabolised?

Answer 31

Clopidogrel is a pro drug that is metabolised by CYP450 to become active. Then metabolised by the liver

Question 32

Side effects of clopidogrel

Answer 32

Abdo pain Diarrhoea Dyspepsia Bleeding disorder

Question 33

How is clopidogrel excreted

Answer 33

50% renal, 50% excreted

Question 34

What is the half life of aspirin

Answer 34

15 minutes but then increases as the dose increases

Question 35

Mechanism of action of dipyridamole

Answer 35

Adjunct to other antiplatelets | Phsophodiesterase inhibitor, prevents breakdown of cAMP, cAMP usually inhibits platelet function.

Question 36

Metabolism of dipyridamole

Answer 36

Hepatic and excreted with bile

Question 37

Side effect of dipyridamole

Answer 37

Positive inotrope and vasodilator(tf flushing and headaches)