Anticogulants Flashcards
what are anticoagulants used for?
Prophylaxis and treatment of thromboembolism
What are the main types of anticoagulants?
Vitamin K antagonists e.g. warfarin Inhibitors of thrombin - unfractionated heparin, LMW heparin- enoxaparin fondapurinux
What is WARFARIN?
A COUMARIN derivative with similar structures to vitamin K Active orall
How does it act?
It blocks vitamin K dependent gamma carboxylation of glutamate residues on residues on factors II, VII, IX and X resulting in the production of modified factors known as PIVKA- proteins in vitamin K absence
What is the importance of the production of these modified factors?
They cannot bind calcium and therefore become INACTIVE IN COGULATION
How long does warfarin take to take effect?
2-3 days to achieve full potential as inactive forms replace active
How are the effects of warfarin monitored?
with the PROTHROMBIN TIME expressed as the INR - the international normalised ratio
What is warfarin’s half life?
long around 40 hours, and it takes as long as 5 days for it to return to normal once stopped.
How is warfarin metabolised?
By HEPATIC microsomal enzymes to INACTIVE 7-hydroxywarfarin
What are the adverse effects of Warfarin?
HAEMORRHAGE - in overdose reverse with clotting factor concentrates of FFP If severe consider vitamin K DRUG INTERACTIONS- induce= barbiturates, carbamazepine inhibit= ethanol, metronidazole TERATOGENICITY -
What is heparin?
A naturally occurring GLYCOAMINOGLYCAN of VARYING MOLECULAR WEIGHT 5000-15000
How is heparin given? is it long or short acting?
injection subcutaneously or iv short acting
How does thrombin work?
It forms a 1:1 complex with ANTI THROMBIN III, a PROTEASE INHIBITOR that INACTIVATES THROMBIN (FACTOR II) when bound to heparin
What also does the heparin- antithrombin II complex inhibit?
FACTOR Xa Factor IX so no formation of factor VIII
How do you measure the effects of heparin?
By the ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT)
Does heparin have a short or long duration?
Short, 4-6 hours
What does LMWH-antithrombin III complex inhibit?
only factor Xa-> LESS BLEEDING
Do LMWHs have a longer or shorter half life?
Longer half life therefore only requires SINGLE DAILY DOSES Prophylaxis doses don’t require monitoring
What are the adverse effects of heparin?
HAEMORRHAGE LESS with LMWH than HEPARIN Bleeding from heparin normally controlled by stopping its administration but in severe cases PROTAMINE SULPHATE ( a basic peptide that combines with the acidic heparin) maybe required ALLERGIC RXN HEPARIN INDUCED THROMBOCYTOPENIA - HIT OSTEOPOROSIS THROMBOSIS- rare
What is fondaparinux?
A PENTASACCHARIDE that inhibits factor Xa
What has fondaparinux been shown to do?
Reduce VENOUS THROMBOEMBOLISM more effectively than LMWH in knee and hip arthroplasty and hip fractures given 6h post surgery or 12h after removal of epidural catheter
What is Melagatran?
a newer DIRECT ORAL THROMBIN INHIBITOR
What Advantages does Melagatran have over warfarin?
wide therapeutic and safety window no monitoring required no interactions with other medication
What would the APTT and PT values do in a patient with Haemophilia A?
- APTT- activated partial thromboplastin time- instrinic pathway
- PT- prothrombin time= extrinsic pathway
- Factor VIII deficiency so APTT Increase , PT same
How would the APTT and PT change with warfarin, dic or factor V or X deficiency?
- Prolonged APTT and PT
- both extrinsic and intrinsic effected
How would the APTT and PT change with Von willebrand’s disease ?
- Deficiency in von willebrand factor a multimeric protein that is required for platelet adhesion.
- VWf is bound to factor VIII so -> reduction in factor VIII increase APTT normal PT
What would give a increased PT and a normal APTT?
- Chronic liver disease
