Anticoagulants, Thrombolytics And Anti Platelets

Question 1

Warfarin- why initially prothrombotic?

Answer 1

Also inhibits production of protein C and S which normally STOP coagulation!

Question 2

Warfarin PKs?

Answer 2

Heavily protein bound!

Question 3

Warfarin- ADRs?

Answer 3

Bleeding/bruising- intracranial, GI, epistaxis

Teratogenic! Not in 1st trimester, or 3rd trimester (baby brain haemorrhage!)

Question 4

Warfarin- DDIs? Drugs that increase effect?

Answer 4

• CYP inhibitors
• protein displacement (NSAIDs)
• anti platelets (aspirin)
• vitamin K deficiency (broad spect antibiotic kill gut bacteria!)

Question 5

Warfarin DDIs? Drugs that decrease effect?

Answer 5

CYP inducers!

Question 6

Warfarin monitoring?

Answer 6

Use INR

• aim for 2.0-3.0 in DVT, PE, AF
• aim for 2.5-4.5 in recurrent thrombosis, prosthetic valve, thrombophilic condition

Question 7

Warfarin- INR above 4.5!!!

Answer 7

Stop warfarin, or reduce dose, if very high/bleeding give fresh frozen plasma and/or vitamin K

Question 8

Heparin- mechanism? LMWH vs unfractioned?

Answer 8

Activate antithrombin III

• unfractioned -> inactivate Xa and thrombin
• LMWH -> inactivated Xa ONLY! As too small!

Question 9

Heparin- administration (both types)

Answer 9

Unfractioned- IV, need loading dose

LMWH- subcutaneous injection

Question 10

Heparin- monitoring?

Answer 10

LMWH- no monitoring needed as predictable response!

Unfractioned- monitor APTT as unpredictable dose response/bioavailability

Question 11

Heparin- ADRs?

Answer 11

Bleeding/bruising, thrombocytopenia (unfractioned), osteoporosis

Question 12

Heparin- uses?

Answer 12

Rapid onset- works before warfarin has effect- DVT, PE, AF
MI, unstable angina
Pregnancy instead of warfarin!

Question 13

Thrombolytics- mechanism?

Answer 13

Increases plasmin, by generating it or converting plasminogen to plasmin -> degradation of fibrin mesh

Question 14

Thrombolytics- ADRs?

Answer 14

Bleeding (brain, GI), streptokinase- anaphylaxis (only use once), hypotension

Question 15

Warfarin- mechanism?

Answer 15

Inhibits vitamin K reductase- decrease synthesis of vitamin K dependent clotting factors (prothrombin, X, VII, IX) takes DAYS to have effect

Question 16

Thrombolytics- contraindications?

Answer 16

Bleeding, anticoagulant therapy, haemophilia, recent surgery,

Question 17

Thromboxane inhibition- mechanism?

Answer 17

Decrease thromboxane (e.g, aspirin inhibit COX-1) -> reduce platelet aggregation and vasoconstriction

Question 18

ADP receptor antagonists- mechanism? And example?

Answer 18

Blocks ADP receptors inhibits ADP/ADP receptor interaction -> inhibits platelet aggregation e.g, clopidogrel

Question 19

GpIIb/IIa inhibitors- mechanism?

Answer 19

Stops fibrinogen binding to GbIIb/a receptors -> inhibits platelet aggregation

Question 20

Heparin- reversal of therapy?

Answer 20

Protamine sulphate - irreversibly binds to heparin causes dissociation of heparin/antithrombin complex