Antiplatelet and Anticoagulant Therapy

Question 1

Describe virchow triad

Answer 1

Hypercoag = factor V leiden, smoking, malignancy, prosthetic heart valves

Endothelial damage = atheroma, hypertension, toxins

Stasis = post-op, long flights, AF, mitral valve disease, post MI

Question 2

Discuss warfarin

Answer 2

Inhibits prod of vit K dependent clotting factors = 2, 7, 9, 10

Warfarin has a delayed onset due to decay of activated clotting factors = heparin cover initially

Oral, good GI absorption

Heavily protein bound = caution with drugs that displace it

Met by liver p450 = caution with liver disease

Can cross placenta = caution teratogenic in 1st trimester, 3rd brain haemorrhage

Question 3

Wha drugs potentiate the effect of warfarin?

Answer 3

Inhib hepatic met = metronidazole, quinolone

Inhib platelet function = aspirin

Reduce vit K from gut bacteria = cephalosporin ABX

Question 4

What drugs inhibit the effect of warfarin?

Answer 4

Anti-epileptics = stim met of warfarin by inducing liver enzymes

Rifampicin (TB)

St Johns Wort (depression, OTC)

Question 5

When is warfarin used?

Answer 5

DVT

PE

AF

Prosthetic valves

Recurrent thrombosis

Question 6

Outline the ADRs of warfarin

Answer 6

Bleeding = intracranial, epistaxis, injection, GI loss

Teratogenic = can cross placenta

Question 7

How can warfarin be reversed?

Answer 7

Parenteral vit K = slow

Fresh frozen plasma = fast

Be carful about giving too much vit K = pt will be anti coag for the next 4 weeks – will have to stay on heparin all that time

Question 8

What is INR?

Answer 8

International normalised ratio

Calculated from PT result

Ratio of a pts prothrombin time to a control sample

Used to monitor how well warfarin is working to prevent blood clotting

Question 9

Discuss heparin

Answer 9

Deactivates 10a, 9a, 11a, 12a, thrombin

Unfractionated (IV) = bind anti-thrombin 3 increasing its activity, inactivates thrombin – MONITOR APTT

Low molecular weight (subcutaneous) = high bioavailability, binds anti-thrombin 3 increasing activity but doesn’t inactivate thrombin

IV/SC as poor GI absorption, rapid onset

Uses = prevent thromboembolism, treatment: DVT/PE, AF, acute coronary syndromes

Question 10

Outline the ADRs of heparin

Answer 10

Bruising, bleeding = intracranial

Thrombocytopenia

Osteoporosis

Question 11

How can the effect of heparin be revered?

Answer 11

Protamine sulphate = dissociates heparin from anti-thrombin 3

If actively bleeding give = protamine

Question 12

What anti-platelet drugs are available?

Answer 12

Aspirin = inhib COX1 irreversibly

Dipyridamole

Clopidogrel = blocks platelet receptor

Glycoprotein 2b/3a inhibitors = block final pathway in platelet aggregation

Question 13

What is the mechanism of anti-platelet drugs?

Answer 13

Block platelets adhesion/activation/aggregation