Antiplatelet Drugs

Question 1

What are the 3 parts of virchows triad?

Answer 1

Abnormalities in blood flow
Abnormalities in blood constituents
Abnormalities in the vessel wall

Question 2

What can cause an abnormality in blood constituents?

Answer 2

Smoking
Surgery- increased clotting factors
Pregnancy

Question 3

What can cause abnormalities in blood flow?

Answer 3

Stasis- either a cardiac abnormality or immobility

Cardiac cause- AF, mitral valve disease, post MI

Immobility- ill health, post op, economy class flying

Question 4

What can cause abnormalities in the vessel wall?

Answer 4

Endothelial damage-
atheroma- MI
Hypertension
Toxins- cigarettes, homocysteine.

Question 5

Which clotting factors are dependent on vitamin K and therefore inhibited by warfarin?

Answer 5

2, 7, 9 and 10

Question 6

Which clotting factor does LMWH inhibit?

Answer 6

Factor Xa.

Question 7

Which clotting factors does the heparin AT complex inhibit?

Answer 7

12,11,10,9 and 2(thrombin)

Question 8

What happens when an atherosclerotic plaque ruptures?

Answer 8

Adhesion, activation and aggregation of platelets via Von Willebrand factor

Activation of clotting factors- fibrinogen—> fibrin—> thrombus formation

Question 9

How do warfarin and similar anti coagulants work?

What consequence does this have for how quickly it has its effects?

Answer 9

Inhibit production of vitamin K dependent clotting factors by stopping conversion of vit K into active reduced form.

Because of this warfarin takes 2-3 days to have effect because there will still be clotting factors in the blood

Question 10

What is the pharmacokinetics of warfarin?

Why is it so important to titrate the dose of warfarin slowly?

Answer 10

Good GI absorption, long half life so needs a loading dose. Heavily protein bound. Hepatic metabolism via CYP450s- is different in all of us so warfarin dose needs to be steadily increased.

Question 11

Which factors are involved in the intrinsic pathway?

Answer 11

12, 11, 9

Question 12

From what kind of injury does the intrinsic pathway arise?

Answer 12

Eg thrombus clot in the vessels.

Question 13

From what kind of injury does the extrinsic pathway arise?

Answer 13

From external tissue injury.

Question 14

What test do we use to measure the intrinsic pathway?

Answer 14

APTT

Question 15

What test do we use to measure the extrinsic pathway?

Answer 15

PT- commonly converted to INR in most labs.

Question 16

On which clotting factor do both the extrinsic and intrinsic pathways converge?

What does this do?

Answer 16

Factor X—> Xa

Xa causes conversion of prothrombin to thrombin and from that fibrinogen to fibrin and with help of factor VIII helps to form a stable clot.

Question 17

What does plasmin do?

Answer 17

Breaks down fibrin clot

Question 18

How can fibrin degradation products be detected in the blood?

Answer 18

D dimer test

Question 19

Which clotting factors does Protein C inhibit?

Why do we need to cover the first 2-3 days of warfarin treatment with LMWH?

Answer 19

VIII and V.
Protein C is also Vit K dependent so protein C levels decrease with warfarin treatment so patient becomes slightly more hypercoaguable.

Question 20

What INR do we aim for in DVT, PE or AF?

Answer 20

2-3

Question 21

What INR do we aim for in mechanical heart valves, recurrent thromboses or thrombophilia?

Answer 21

2.5-4.5

Question 22

What drugs inhibit warfarin by inducing its CYP450 enzyme?

Answer 22

Antiepileptics
Rifampicin
St johns wort

Question 23

Which drugs potentiate warfarin by inhibiting its enzyme?

Answer 23

Amiodarone, quinolone, metronidazole, cimetidine, alcohol.

Cephalosporin reduces vit K from gut bacteria

Aspirin inhibits platelet function so exaggerates effect of warfarin.

Question 24

How is warfarin overdose reversed?

Answer 24

Stop warfarin
Then either:
Fresh frozen plasma
Prothrombin complex concentrate
IV vit K

Question 25

What are the two major types of heparin?

What is the difference?

Answer 25

Low molecular weight heparin
Unfractionated heparin

Unfractionated heparin can bind to AT III (and activate it) and other clotting factors simultaneously, LMWH is not big enough for this, therefore unfractionated heparin has a larger anticoagulative effect.

Question 26

Which clotting factor does LMWH affect?

Answer 26

Xa

Question 27

What are the pharmacokinetics of LMWH?

Answer 27

Absorbed uniformly, injected subcutaenously to achieve high bioavailability.
Long half life
Predictable dose response
Cleared by kidneys

Question 28

Which clotting factors does unfractionated hepatin inhibit?

Therefore which bleeding time needs to be measured?

Answer 28

2, 9, 10, 11 and 12

APTT

Question 29

What are the pharmacokinetics of unfractionated heparin?

Answer 29

Poor Gi absorption and variable bioavailability to commonly subcut/ IV. Rapid onset

Question 30

What is the benefit of using heparin in pregnancy in place of warfarin?

Answer 30

It is not teratogenic

Question 31

How is heparin overdose reversed?

Answer 31

Stop heparin
Give protamine sulphate.
This dissociates heparin from its ATIII and irreversibly binds to heparin.

Question 32

What are some of the newer ACAs?

Answer 32

Aspirin
Dipyridamole
Clopidogrel
Glycoprotein IIb, IIIa inhibitors

Question 33

What is the mechanism of action of dipyridamole

Answer 33

Phosphodiesterase inhibitor

Question 34

What is the mechanism of action of clopidogrel and when is it indicated?

Answer 34

ADP antagonist, inhibits platelet aggregation.

Indicated in ACS, PCI.