By Duy Thai
HAEMOSTASIS
Definitions
• Thrombus:
• An aggregate of platelets and fibrin which occurs at the site of injury.
• Embolus:
• A portion of thrombus which has broken off from the primary site and impacted at a distant site
ORAL ANTICOAGULANTS
• Coumarin derivatives:.
• Warfarin
Mechanism of action:
• Prevents the activation of vitamin K dependent clotting factors (II, VII, IX and X)
• These clotting factors are synthesised by the liver and converted into an active form via γ carboxylation (catalysed
by vitamin K)
CH2 CH2
Vit K Vit K
(Hydroquinone) (Epoxide form)
Warfarin
• Warfarin is only active in vivo
• Because it acts to inhibit a natural physiological process which only occurs in the liver. If you take a sample
of blood, it already has the active coagulation factors, and so adding warfarin does not prevent coagulation
of stored blood.
Pharmacokinetics:
• There is a delayed onset of activity.
• The effects of warfarin are only seen when the already active circulating coagulation factors are broken
down. Any new ones which are made by the liver will be inactive. Warfarin does not affect the normal
circulating active factors.
• Orally active
• Rapidly absorbed
• Strongly bound to plasma proteins (approximately 99% is bound)
• This means that there is a lot of drug interaction with other drugs which are bound to plasma proteins.
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1997 Clinical pharmacology
By Duy Thai
INJECTABLE ANTICOAGULANTS
• Heparin
Properties
• Low molecular weight forms of heparin
• Is a natural long chain mucopolysaccharide found in most cells of the body
• Specific arrangement of sulphate groups (high negative charge), therefore not absorbed well from the GIT
Mechanism of action
• Promotes the action of antithrombin III
• Heparin binds to antithrombin III and changes its conformation. thus exposing an active site
• The activated antithrombin III + Heparin complex inactivates active clotting factors 1000 times more rapidly than
antithrombin III on its own
• Low molecular weight heparin has more specificity towards affecting factor Xa
Side effects
• Never given intramuscularly because it can lead to haemorrhage in the muscle (given IV or subcutaneously)
• Thrombocytopenia (often transient and mild)
• Low molecular weight heparin has less effects on platelet number
• Osteoporosis (only occurs with long term use of heparin - Greater than 6 months)
• Heparin is only used for short periods (for acute treatment - NOT long term prophylaxis)
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1997 Clinical pharmacology
By Duy Thai
Platelet membrane
PLA2
Arachidonic acid
COX
TxA2
THROMBOLYTICS
Plasminogen Plasmin
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1997 Clinical pharmacology
By Duy Thai
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