Pharmacology of Haemostasis and Coagulation

Question 1

Types of anticoagulants

Answer 1

Oral
Hearings
Direct oral anticoagulants (DOACs)

Question 2

What is warfarin?

Answer 2

Oral anticoagulants

Vitamin k antagonist

Question 3

What does warfarin do?

Answer 3

Blocks vitamin k reductase which is needed for vitamin k to act as a cofactor
Inhibits post-translational modification, therefore no carboxylation of glutamic acid residues
Production of proper coagulation factor is inhibited

Question 4

What is warfarin used for?

Answer 4

Prevent thrombosis:

Patients with replaced heart valves, atrial fibrillation, PE, DVT

Question 5

How long does it take for warfarin to take effect?

Answer 5

Several days

Question 6

What is warfarin monitored by?

Answer 6

International normalised ratio with a specific target value and adjust dose

Question 7

Problems with warfarin

Answer 7

Many drug interactions - may be potentiated by a range of drugs
- may be reduced by enzyme inducers
Increased risk to bleeding

Question 8

Give an example of injectable anticoagulants

Answer 8

Unfractionated heparin or Low Molecular Weight Heparin

Eg. Enoxaparin, tinzaparin

Question 9

What do injectable anticoagulants do?

Answer 9

Activate antithrombin III (natural protein)

Antithrombin inactivates some clotting factors and thrombin by complexing with serine protease of the factors

Question 10

Difference between injectable anticoagulants and warfarin

Answer 10

IAs are immediate and subcutaneous

Question 11

Use of heparin

Answer 11

Prevent thrombosis (particularly DVT), used to prevent clots
Used while warfarin takes effect
Unfractionated heparin monitored with APTT

Question 12

Example of DOAC

Answer 12

Dabigatran - oral thrombin inhibitor

Question 13

What do DOACs do?

Answer 13

prevents thromboembolism by inhibiting the coagulation factors in the cascade

Question 14

Why are DOACs better than warfarin?

Answer 14

less bleeding
fewer drug interactions
does not require monitoring
equally as effective

Question 15

Why are DOACs not better than warfarin?

Answer 15

effects are less easily reversed

expensive antidote

Question 16

What are prostacyclin/nitric oxide?

Answer 16

endothelial derived vasodilators

Question 17

What does prostacyclin do?

Answer 17

PGI2 - prevents platelet aggregation

acts on platelets to increase cAMP

Question 18

What does thromboxane do?

Answer 18

promotes aggregation, decreases cAMP

Question 19

What does nitric oxide do?

Answer 19

prevents both platelet adhesion and aggregation by increasing platelet cGMP

Question 20

Give examples of antiplatelet drugs?

Answer 20

low dose aspirin (75mg)

dipyridamole

Question 21

What is low dose aspirin used for?

Answer 21

prevent MI in ps who have previously had a MI
(not for primary prevention)
reduces incidence of stroke

Question 22

How does low dose aspirin work?

Answer 22

inhibits cyclo-oxygenase irreversibly so free arachidonic acid cannot be made into endoperoxides which in turn form PGI2 and thromboxane
thromboxane is a platelet and therefore has no nucleus whereas PGI2 is an endothelial cell and therefore the nucleus regenerates COX

Question 23

What is dipyridamole?

Answer 23

antiplatelet drug

Question 24

What is dipyridamole used for?

Answer 24

prevention of thrombosis

used in conjunction with aspirin, enhances effect of aspirin

Question 25

How does dipyridamole work?

Answer 25

phosphodiesterase inhibitor - prevents breakdown of cAMP and cGMP (which are broken down by phophodiesterase) therefore inhibits aggregation also inhibits adenosine uptake

Question 26

What is GP IIb/IIIa?

Answer 26

expressed from ADP from aggregating platelets | binds fibrinogen which leads to cross-linking of platelets

Question 27

What does clopidogrel do?

Answer 27

inhibits ADP induced expression of GP, ie prevents ADP activating platelets

Question 28

When is clopidogrel used?

Answer 28

for ps who can't take aspirin | used with aspirin after a heart attack

Question 29

Why is aspirin not used for primary prevention?

Answer 29

risk of gastric bleeding

Question 30

What is abciximab?

Answer 30

monoclonal antibody against GP IIb/IIIa

Question 31

When is abiciximab used?

Answer 31

ps undergoing angioplasty (catheter and balloon to open up coronary artery)

Question 32

Give an example of fibrinolytic drug/protein

Answer 32

alteplase

Question 33

What is fibrinolysis?

Answer 33

break down of fibrin endogenous system to dissolve clots, activated with clotting system plasminogen becomes activated to form plasmin

Question 34

What is plasmin

Answer 34

part of fibrinolysis enzyme which digests fibrin of the clot and also some of the clotting factors dissolves it

Question 35

What do fibrinolytic agents do?

Answer 35

activate plasminogen to plasmin conversion

Question 36

What are thrombolytics used for?

Answer 36

given after MI to dissolve thrombus that has caused blockage of coronary arteries and the MI pulmonary embolism thromboembolic stroke

Question 37

What are thrombolytics used with?

Answer 37

with aspirin, but need care can cause bleeding

Question 38

What is alteplase used for?

Answer 38

ischaemic strokes dissolves clot and restores blood flow, saving neurons must be given <4 hours post-stroke