Pharmacology Of Haemostasis Flashcards
(39 cards)
Definition of anticoagulant
Interferes with process of fibrin plug formation to reduce or prevent coagulation
How does warfarin work
Inhibits the reduction of vitamin k which is needed as a cofactor in gamma carboxylation of the glutamate residue of clotting factors II, VII, IX, X
During the gamma carboxylation Vit k is converted to k 2,2 epoxide, warfarin stops its conversion (reduction) back to Vit k due to its structural similarity to Vit k
What are the half lives of the Vit k dependant clotting factors
II 60hrs
VII 6 hrs
IX 24hrs
X 40hrs
Other types of anticoagulant that act similar to wararin
Nicoumalone (a coumarin)
Phenindione (an inandione)
Isomerism of warfarin
L and D forms
Given as an racemic mixture
How fast does oral warfarin take to reach peak plasma concentration
Bioavailability
1 hr
Bioavailability 100%
Type to peak warfarin effect
36-48hrs
Degree of protein binding of warfarin
To what
99%
Albumin
Breast feeding and warfarin?
Enters breast milk causing issue as newborn gut flora not yet developed for producing Vit k
Methods of interaction with warfarin
Competition for protien binding sites
Increased hepatic binding
Inhbition or induction of hepatic enzymes
Reduced Vit k synthesis
Synergistic anti haemostatic action
Which drugs may displace warfarin from proteins
NSAIDs, choral hydrate, oral hypoglycaemics, diuretics, amiodarone
Why might abx influence warfarin
Alter gut bacteria reducing Vit k synthesis
How does oestrogen effect warfarins action
Increases production of Vit k dependant clotting factors
Effect of cholestyramine on wawrfarin
Binds it reducing effect
How do heparins work
Binding antithrombin increasing its activity on factors IIa IXa Xa XIa, XIIa by confimational change and binding to both the antithrombin and the clotting factor (all but Xa)
Reduces platelet aggregation (due to reduced thrombin)
Increases vascular permeability
Releases lipoprotein lipase into plasma
Structure of heparin
Sulphated acid glycosaminoglycans (mucopolysaccharides)
Chain about 50 sugar residues on a protein Skelton
Molecular weight 3000-40000 daltons
Strong negative charge
Where is endogenous heparin found
Lungs, arterial walls, mast cells
What are lmwhs
How do they work
Fragments of depolymerised heparin purified to contain the antithrombin specific binding site
All inhibit Xa, much reduced antithrombin activity but do require antithrombin for effect
Molecular weight of lmwh
3000-8000 daltons
Advantages of lmwh
Minimal alteraltion to platelet function
Better interop haemostasis
Possible better vte prophylaxis
Sc administration
Once daily dosing
More predictable (much less protein bound)
What is the issue with acute illness and heparin function
Heparin is bond to acute phase proteins so acute illness increases these levels altering Clincial effect
Heparin metabolism
Half life
Hepatic, renal and reticularendothelial system
40-90 mins
Time to peak action of lmwh and time to degrade to half action
Peak in 3-4 hrs
Degrades to half in 12 hrs
Metabolism of lmwh
Renal elimination
