Anticoagulant drugs Flashcards
Clinical uses of anticoagulants
- Prevention of deep vein thrombosis
- In treatment of deep vein thrombosis/ prevention of pulmonary emboli
- Prevention of thrombosis on prosthetic heart valves
Mechanism of action of warfarin
- It prevents the carboxylation of factors II, XII, IX and X by inhibiting vitamin K reductase
- The tissue factors cant then localize to the right place (on platelets) and cant stimulate the conversion of fibrinogen to fibrin
clinical use of warfarin
Prolonged therapy
administration of warfarin
- Orally
* Is rapidly absorbed by GI tract
Rate of onset of warfarin
- Rate of onset is slow as already carboxylated tissue factors have to be broken down and factor VII has a half life of 6h which is the fastest
- Rate of onset therefore 6-12h
duration of action/ half life of warfarin
Duration 4-5 days
It strongly binds to plasma proteins
Its own half life = 40 hours and is metabolized in the liver
Warfarins actions are potentiated by
- Drugs which displace warfarin from plasma proteins (Aspirin) → As it would cause an increased amount of free warfarin in the blood stream
- Drugs which interfere with liver function (sulphonamides)→ reducing the livers function would decrease warfarin clearance
- Drugs which interfere with platelet function (NSAID)
- Liver disease (decreases factor production and warfarrin clearance)
- Decreased Vit K availability
Warfarins actions are decreased by
- Drugs which induce metabolizing enzymes (Barbiturates) → so warfarin clearance is increased
- Promoted clotting factor synthesis (Vitamin K)
- Reduced warfarrin adsorption (colestipol) → many patients with DVT also have high LDL levels so are on drugs to prevent absorption in the gut
Unwanted side effects of warfarin
•Haemorrhage – bowel or brain
who can warfarin not be administered to
•Pregnant women as it is teratogenic
What is the mechanism of action of heparin
- It has a negative charge and binds and activates antithrombin III (AT3) which has a positve charge
- Antithrombin III inhibits Factor IIa (thrombin) and Factor Xa
- Heparin/ AT3 more potent action at factor IIa than factor Xa
Clinical use (time) of heparin
•Acutely (short term therapy)
Limitations in heparin use
- Activity modified by platelet factor 4 which is released from platelts and inhibits heparin action
- If factor Xa is already bound to fibrin, it cannot interact with AT3/heparin complex
Administration of heparin
IV
pharmacokinetics of heparin
- Complex due to high plasma protein binding
- There is an initial rapid removal of heparin due to binding to endothelial and macrophage cells therefore an initial big bolus is given to saturate this followed by slow infusion
- Slower subsequent removal by renal excretion
onset of action of heparin
•Immediate if IV
Unwanted side effects of heparin
- Haemorrage → if so treat with the heparin antagonist protamine sulphate
- Thrombosis → rare, associated with antibodies against heparin causing endothelial damage
- Occasional osteoporosis, hypersensitivity and hypoaldosteronism
Examples of heparin
- Heparin
- Calciparine
- Minihep
- Monoparin
what is the mechanism of action of LMW heparin
- Activate antithrombin III
* Can only inhibit factor Xa (not IIa)
How is LMW heparin administered
•IV or SC (subcutaneously)
pharmacokinetics of LMW heparin
•It does not bind to plasma proteins so the kinetics are simpler
onset of action of LMW heparin
rapid
Bad qualities of LMW heparin
•Acts only on factor Xa
Good qualities of LMW heparin
- Not neutralized by platelet 4
- Can administer subcutaneously
- Much less complex pharmocokinetics
Examples of LMW heparin
•Certoparin
•Dalteparin
Enoxaparin
What are anticoagulant drugs primarily used for
Venous thrombosis
