308 Antiplatelet and antithrombotic drugs

Question 1

What is the intrinsic coagulation cascade?

Answer 1

XII - XI - IX - VIII

then converges at factor X

Question 2

What is the extrinsic coagulation cascade?

Answer 2

III - VII

then converges at factor X

Question 3

Name some DOAC’s that work on factor IIa

Answer 3

Riveroxaban
Apixaban

Question 4

Name a DOAC that works on factor IIa

Answer 4

Dabigatran

Question 5

How does Warfarin work?

Answer 5

It’s a vitamin K antagonist that prevents the gamma-carboxylation of factors II,VII,IX,X

Question 6

What is the prothrombin time?

Answer 6

Tells you about the extrinsic pathway

It’s monitored using the international normalised ratio (INR)

Question 7

What is the usual target INR?

Answer 7

2.5 for DVT/PE or AF
3.5 for VTE or metal heart valves

Question 8

What is VTE?

Answer 8

Venous thromboembolism

Question 9

Where is warfarin metabolised?

Answer 9

In the liver

Question 10

How long does warfarin take to achieve therapeutic effects?

Answer 10

At least 3 days

Question 11

Which drug inhibits protein S and C?

Answer 11

Warfarin

Question 12

What is protein S?

Answer 12

It’s the normal substance in the body that prevents clotting

Protein S deficiency causes blood to clot too easily

Question 13

What is protein C?

Answer 13

It provides important control of blood coagulation by regulating the activities of factor VIIIa (FVIIIa) and factor Va (FVa), cofactors in the activation of factor X and prothrombin

Deficiency causes blood to clot too easily

Question 14

How is Warfarin prescribed?

Answer 14

The patient should be given LMW heparin until the INR is 2

Question 15

What are the interactions of Warfarin?

Answer 15

-Anything to so with CYP450
Enzyme inhibitors will potentiate warfarin and enzyme inhibitors will inhibit warfarin

-Alcohol
Chronic alcoholism inhibits warfarin

-Warfarin binding control due to albumin, absorption of vitamin K in GI tract, synthesis of vitamin K factors by the liver, hereditary resistance

Question 16

What are the side effects of Warfarin?

Answer 16

-Teratogenic (LMW heparin is used in pregnancy)
-Significant haemorrhage risk
-Minor bleeds
-Skin necrosis
-Alopecia

Question 17

How is Warfarin reversed?

Answer 17

Give activated prothrombin complex
Eg. Octaplex or Beriplex

It contains vitamin K dependent factors II, VI, IX, X

Fresh frozen plasma (FFP) can be used but is not optimal

Question 18

How does Heparin work?

Answer 18

It’s a mucopolysaccharide that potentiates anti-thrombin and irreversibly inactivates factor IIa and Xa

Question 19

What are the 2 different formulations of heparin?

Answer 19

Unfractionated heparin given by IV infusion

Low molecular weight heparin given as an injection

It’s safe in pregnancy

Question 20

Why is unfractionated heparin rarely given?

Answer 20

Because of inconvenience of administration (IV)

Question 21

Where is unfractionaed heparin metabolised?

Answer 21

In the liver

Question 22

What drug partially reverses heparin?

Answer 22

Protamine sulphate

Question 23

What is Heparin-induced thrombocytopaenia (HIT)?

Answer 23

A rare complication of heparin
Suspect if platelet count falls on heparin

It’s a paradoxical prothrombotic condition that can cause a VTE

Question 24

How is HIT diagnosed?

Answer 24

Using the HIT screen

Then alternative anticoagulation is used

Question 25

Heparin is prescribed according to the patient what?

Answer 25

Weight

Question 26

Name some LMW heparin formulations

Answer 26

Tinzaparin (Innohep)
Enoxaparin (Clexane)
Dalteparin (Fragmin)

Question 27

Where is LMW heparin metabolised?

Answer 27

In the kidney

Creatinine clearance must be at least 30ml/min

Question 28

What is the drug Argatroban for?

Answer 28

A direct thrombin inhibitor

Used in place of heparin in patients with HIT

Question 29

What is the drug Danaparoid for?

Answer 29

A type of anticoagulant

A heparin-like compound

Question 30

What is the drug Arixtra?

Answer 30

It potentiates anti-thrombin by inhibiting factor Xa

Question 31

What are DOAC’s?

Answer 31

Direct oral anti-coagulants

Developed as an oral alternative to warfarin, no monitoring is required

Question 32

What are the 2 classes of DOAC’s?

Answer 32

Direct thrombin (IIa) inhibitor

Direct factor Xa inhibitor

Question 33

How does Rivaroxaban compare to Apixaban?

Answer 33

Rivaroxaban: direct factor Xa inhibitor dosed OD

Apixaban: anti-Xa inhibitor dosed BD. It’s less affected by renal function and can be used at a reduced dose if renal function in impaired

Question 34

What are the indications for Rivaroxiban or Apixaban?

Answer 34

VTE prophylaxis
treatment for DVT and PE
Stroke prevention in AF

Question 35

What is the drug Dabigatran used for?

Answer 35

VTE prophylaxis
treatment for DVT and PE
Stroke prevention in AF

Question 36

Which drug is Praxbind (Idarucizumab)used to reverse?

Answer 36

Dabigatran

It bind to Dabigatran and blocks its activity

Question 37

Name some anti-platelet drugs

Answer 37

Aspirin – cyclo-oxygenase inhibitor
Clopidogrel – ADP receptor blocker

Dipyridamole – inhibits phosphodiesterase
Prostacyclin – stimulates adenylate cyclase

Glycoprotein IIb/IIIa inhibitors:
Abciximab – monoclonal antibody
Eptifibatide – snake venom derivative
Tirofiban – blocks platelet aggregation

Question 38

When are fibrinolytic drugs used?

Answer 38

Work by by converting plasminogen to plasmin

Administered systemically in acute MI, recent thrombotic stroke, major PE, or massive iliofemoral thrombosis

Question 39

Give examples of fibrinolytic agents

Answer 39

Tissue Plasminogen Activator (tPA, Alteplase)
Also streptokinase and urokinase