Anticoagulants & antiplatelets

Question 1

What are the 2 main classes of anticoagulant drugs

Answer 1

Warfarin

Heparin

Question 2

Warfarin:
Mechanism of action
Indications for use
Pharmacokinetics
ADRs

Answer 2

Vitamin K competitive antagonist: prevents production of vitamin K depending clotting factors: II/prothrombin, VII, IX, X)

Used in DVT, PE, AF, mechanical prosthetic hear valves

Good GI absorption, so given Orally
Preferred from long term anti-coagulation
Slow onset and offset of action
Heavily protein bound and can be displaced to have greater effect (e.g. With albumin)
Metabolised via CYP so affected by inducers and inhibitors
Dose monitoring via INR

ADRs: haemorrhage (esp GI), bruising, teratogenic

Question 3

What is INR

Answer 3

International normalised ratio
time taken for blood to clot
high = poor clotting
Aim 2-3 for DVT, PE,AF

Question 4

What are the main drugs potentiating and inhibiting warfarin

Answer 4

Potentiating (increase INR)
Inhibit hepatic metab (amiodarone, quinolone, cimetidine, alcohol, metroniazole)
Inhibit platelet function (aspirin)
Reduce vitamin K From gut bacteria (cephalosporin)

Inhibiting (reduce INR)
Antiepileptics
Rifampicin
St john’s wort, grapefruit juice

Question 5

How is warfarin overdose treated

Answer 5

Warfarin a competitive vitamin K antagonists: so can be displaced by excessive vitamin K (slowly)

Faster reversal: fresh frozen plasma: activate clotting factors

Question 6

Heparin:
Main Mechanism of action
2 subdivisions
Indications
ADRs

Answer 6

Acts on anti-thrombin III to inhibit mainly clotting factor II (thrombin) and Xa

Subdivided into unfractionsted and low molecular weight heparin

LMWH usually preferred in prophylaxis of venous thromboembolism because lower risk thrombocytopenia
Also used in DVT, PE (prior to warfarin to cover whilst loading dose achieved), MI, unstable coronary artery disease
Used in surgery as has faster offset than warfarin

ADRs: haemorrhage, thrombocytopenia (autoimmune: activation of more platelets, depletion of platelets and thrombosis)

Question 7

What are the main differences between unfractionated and LMW heparin

Answer 7

UFH:
Non-linear dose response, unpredictable binding to cells (variable bioavailibility), needs monitoring with APTT test

LMWH:
Predictable dose response, less binding to cells and endothelium (predictible bioavailibility), not monitoring required

Question 8

What are the 2 types of anti-platelets

Give some examples

Answer 8

Thromboxane A2 inhibitors
E.g. Aspirin, dipyridamole

Platelet ADP-receptor antagonists
E.g. Clopidogrel

Question 9

How does aspirin work as an anti-platelet

Answer 9

COX enzyme inhibitor

Prevents thromboxane A2 production and platelet aggregation

Question 10

How does dipyridamole work as an anti-platelet

Answer 10

Inhibits phosphodiesterase enzymes to inhibit thromboxane A2 production

Question 11

What are the reasons for thrombus formation

Answer 11

Virchov’s triad:

Abnormality of vessel wall (endothelial damage e.g. Atheroma, htn)

Abnormality to blood constituents (hypercoagulability: genetic or acquired e.g. Smoking)

Abnormality to blood flow (stasis: e.g. Immobility, AF)