Clotting drugs

Question 1

How does aspirin work?

Answer 1

Anti platelet. Irreversibly inactivates platelet COX-1 enzyme which reduces the production of Thromboxane A2 from prostaglandin H2. This limits thromboxane A2’s normal function of platelet aggregation and vasoconstriction.

Question 2

Why is aspirin irreversible?

Answer 2

Blocks COX-1 enzyme in platelets. Platelets cannot regenerate this enzyme so won’t be able to produce thromboxane A2 for the rest of their lives

Question 3

How does clopidogrel work?

Answer 3

Blocks ADP receptors (P2Y12 subtype) on surface of platelets which reduces platelet aggregation. Doesn’t affect COX enzyme so can work synergistically with aspirin

Question 4

How do glycoprotein IIb/IIIa receptors anatagonists work? E.g. abciximab, tirofiban

Answer 4

Stop platelets from aggregating

Question 5

Why are antiplatelets generally only recommended for arterial and intracardiac thombi and not venous thrombi?

Answer 5

Arterial + intracardiac thrombi are rich is platelets whereas venous thrombi have a low platelet content.

Question 6

Briefly outline three indications for anticoagulant drugs

Answer 6

1) Stroke prevention in high risk groups e.g. AF
2) VTE- treatment and prophylaxis e.g. bed bound patients
3) Arterial thrombotic disease- ACS/MI

Question 7

What route is unfractionated and low molecular weight heparin administered via?

Answer 7

SC

Question 8

What can be given to reverse heparin?

Answer 8

Protamine sulphate

partial reversal in LMWH and full reversal in UFH

Question 9

How do heparins and fondaparinux work?

Answer 9

Indirectly inhibit factor 10a by inhibiting antithrombin 3.

Question 10

What are the advantages of fondaparinux compared to UFH and LMWH?

Answer 10

No routine coagulation monitoring (UFH)
No risk of HIT (Heparin induced thrombocytopenia)
lower risk of bleeding

Question 11

How does naturally occurring heparin act as an anticoagulant?

Answer 11

Acts as a cofactor for antithrombin 3 which inactivates clotting factors flowing away from site of injury

Question 12

How does Warfarin work?

Answer 12

Vitamin K antagonist.
Inhibits vitamin K epoxide reductase which is needed to convert Vitamin K back into its reduced form to synthesise clotting factors.

Question 13

What are the vitamin K dependent clotting factors?

Answer 13

2, 7, 9, 10

Question 14

What are the disadvantages of warfarin?

Answer 14

Diet restrictions, regular monitoring via INR, Narrow therapeutic window, interacts with other drugs e.g. antibiotics, slow on and offset of action and unpredictable response

Question 15

What can reverse warfarin?

Answer 15

PCC (Prothrombin complex concentrate) or vitamin K

Question 16

What type of drug are; rivaoxaban, apixaban and edoxaban? How do they work?

Answer 16

NOACs- new oral anti-coagulant agents. Directly inhibit factor 10a

Question 17

Dabigatran is a NOAC but works differently to other NOACs. How?

Answer 17

Directly inhibits thrombin (rather than factor 10a)

Question 18

What are the disadvantages of NOACs?

Answer 18

No antidote available - apart from dibigatran . Must be immediately stopped in bleeding

Question 19

When plasmin dissolves a fibrin clot what products are formed?

Answer 19

Fibrin degradation products (FDPs) and D-dimer

Question 20

Name a first generation thrombolytic drug

Answer 20

Streptokinase

Question 21

Name a second generation thrombolytic drug

Answer 21

tissue plasminogen activator (t-PA)

Question 22

Name a third generation thrombolytic drug

Answer 22

recombinant plasminogen activator (r-PA)

A TNK mutant (TNK=tenectaplase)

Question 23

List some indications for thrombolytic drugs

Answer 23

Acute MI, ischaemic stroke, peripheral arterial thrombosis, PE, occluded haemodialysis shunts

Question 24

Are anticoagulants or anti platelets suitable for arterial and venous thrombosis?

Answer 24

Anticoagulants- venous thromboses tend to have a low platelet concentration so anti platelets aren’t as effective