Anticoagulants

Question 1

How does aspirin work?

Answer 1

At low doses it:

• Inhibits COX1
• COX1 is needed to form thromboxane A2 (TXA2)
• Reduction of TXA2 inhibits platelet aggregation (irreversible)

Question 2

Indications of aspirin?

Answer 2

• prevention of stroke, TIA and ACS
• post Percutaneous Coronary Intervention and stent
• prevention of MI in stable angina

Question 3

Contraindications for aspirin?

Answer 3

active peptic ulcers, bleeding disorders, renal impairment

Question 4

How do clopidogrel and prasugrel work?

Answer 4

Antiplatelets !!!

binds irreversibly to P2Y12 receptor, inhibiting ADP from binding to it

This inhibits GPIIb/IIIa receptors from being activated.

Question 5

When do we use P2Y12/ADP receptor antagonists? eg. clopidogrel

Answer 5

post MI, etc.

Question 6

How does abciximab work?

Answer 6

Antiplatelets !!!!

irreversibly blocks GPIIb/IIIa receptors

This inhibits fibrinogen from binding

This reduces aggregation

It is more completely inhibiting than eg. clopidogrel, as GP2b/3a receptors are found at the end of the pathway.

Question 7

What is a SE of abciximab?

Answer 7

• huge bleeding risk

- Thrombocytopenia

Question 8

How does dipyridamole work?

Answer 8

Antiplatelets!!!

phosphodiesterase inhibitor.

prevents cAMP and cGMP degradation

this inhibits expression of GP2b/3a receptors

This reduces aggregation

Question 9

When is dipyridamole used?

Answer 9

prevents ischaemic stroke and TIA

used as adjunct to oral anticoagulants after valve replacement

Question 10

Name a fibrinolytic agent “clot buster” and an agent that inhibits fibrinolysis

Answer 10

“clot buster” = streptokinase, alteplase, reteplase

Inhibitor of fibrinolysis = tranexamic acid

Question 11

How does warfarin work?

Answer 11

Anticoagulant !!!

Inhibits conversion of vit K to active reduced form (inhibits VK epoxide reductase)

Inhibits synthesis of vit K dependent clotting factors
(Prothrombin II, X, IX, VII)

(Delayed onset of action as circulating active clotting factors remain for a while)

Question 12

when is warfarin used?

Answer 12

DVT/PE prophylaxis and treatment

AF with high stroke risk

mechanical prosthetic valves

following ortho surgery (stasis)

***heparin cover if anticoagulation needed immediately, due to delayed onset of action.

Question 13

when is warfarin contraindicated?

Answer 13

functional 2C9 polymorphism (CYP2C9 metabolism)

amiodarone, clopidogrel, metronidazole, etc inhibit hepatic metabolism esp CYP2C9

pregnancy (1st and 3rd trimesters)

St Johns wort, barbiturates, etc accelerate warfarin metabolism

Question 14

How do you stop warfarin?

Answer 14

Reverse by using vitamin K1, prothrombin complex concentrate IV, fresh frozen plasma, and stop warfarin.

Question 15

How does unfractionated heparin work?

Answer 15

it binds to antithrombin (ATIII) and causes a conformational change

ATIII inactivates thrombin IIa, factor Xa, IXa, XIa and XIIa

(To inhibit IIa, heparin must simultaneously bind ATIII and IIa)

IV infusion or SC as poor GI absorption

Question 16

How does dalteparin work?

Answer 16

It is a low molecular weight heparin

works same as heparin, but more predictable dose response
(does not bind to endothelial cells, plasma proteins, macrophages)

Less likely to cause thrombocytopenia

Targets Xa specifically.
Does not inactivate thrombin IIa

Question 17

When are heparins indicated?

Answer 17

DVT, PE, AF
- prior to warfarin as quicker onset prior to warfarin loading

post MI or NSTEMI, Acute Coronary SYndrome

During pregnancy as does not cross placenta

prevention of venous thromboembolism perioperative (LMWH)

Question 18

When are heparins contraindicated?

Answer 18

hepatic and renal compromise

Question 19

How do you reverse heparins?

Answer 19

Protamine sulphate dissociates heparin from ATIII

Question 20

How do apixaban and rivaroxaban work?

Answer 20

Inhibits free Xa and Xa bound to ATIII
(Direct Xa inhibition)

No effect on thrombin IIa

hepatic metabolism, excreted partly by kidneys

Question 21

How does dabigartran work?

Answer 21

Direct competitive thrombin inhibitor (both circulating and thrombus bound IIa)