Anticoagulant drugs COPY Flashcards
what does warfarin target
vitamin K synthesis
vit k needed to produce clotting factors 2,7,9 and 10
what does heparin target
anti-thrombin - makes it stronger
what are the indications for anticoagulant drugs
Venous thrombosis
Atrial fibrillation
(to prevent clot forming in the left atrium (which isn’t contracting properly leading to stasis and pooling of blood) and the clot could break off into LV through carotids to the brain causing stroke).
treatment of cardioembolic strokes vs atheroembolic
cardioembolic - anticoagulants bc its coming from AF in the heart, pooling of blood and fibrin clot
atheroembolic - anti platelets, due to atheroma in situ
what are the naturally occurring anticoagulants
Serine protease inhibitors - anti thrombin
Protein C (factor V)
Protein S (Factor VIII)
what natural anticoagulants are vitamin K reliant
protein C
protein S
so warfarin immediately drops protein C and protein S levels increasing risk of thrombosis
what does heparin do
has an immediate effect to increase the action of anti-thrombin
given IV or SC
IV = unfractionated (needs a lot of monitoring for right does).
SC= low molecular weight heparin (more predictable and given on a weight basis)
how does heparin increase the effect of antithrombin
joins antithrombin and thrombin together and stabilises them
also joints antithrombin and factor X to prevent prothrombin being converted to thrombin
when is unfractionated heparin used
complicated patients with thrombosis but also risk of bleeding
can stop it quickly as it has a v short half life
what is the predominant target for LMWH vs unfractionated
LMWH - more factor Xa
Unfractionated -more thrombin
which test is most sensitive for monitoring heparin
APTT - activated partial thromboplastin time
Thrombin feeds back to activate factors VIII and IX making this test more sensitive than prothrombin time
complications of heparin
Bleeding
heparin induced thrombocytopenia (with thrombosis) antibodies to the heparin and platelets - platelets tend to aggregate
osteoporosis with long term use
what to do if bleeding on heparin
stop heparin - v short half life
can give antidote to heparin - Promatine sulphate
complete reversal for unfractionated and partial for LMWH because it only reverses binding to thrombin not factor Xa
what oral agents do you use if a patient needs long term anticoagulation
Warfarin
3-6 months for first venous thrombosis
if more than one event = lifelong
How does warfarin work
inhibits vitamin K
used for carboxylation of clotting factors 2,7,9 and 10
also used for protein C and protein S (so when you first give warfarin you make risk of thrombosis worse)
where are vitamin K dependent clotting factors made
Liver
how is vit K absorbed
fat soluble vitamin (ADEK)
absorbed in proximal intestine
needs bile salts to be absorbed
what is the action of vitamin K
carboxylation of glutamic acid residues in factors II, VII, IX and X and protein C and S
leads to synthesis of non-functional clotting factors
why does heparin need to be prescribed with warfarin
because of the initial decrease in protein C and S so makes you more thrombotic
when would you not need to give heparin with warfarin
if you start giving it v slowly so the decrease in protein C and S is not as rapid
has a narrow therapeutic window so need to monitor therapy
dose should be given at the same time every day
how do you monitor warfarin
prothrombin time - most sensitive as factor VII has the shortest half life
will also effect X and IX so also prolongs APTT but not as much as PT
what is the INR
score used for monitoring warfarin therapy
international normalised ration
a mathematical correction of normal PT and mean PT
risk factors for bleeding on warfarin
intensity of coagulation
contaminant clinical disorders
contaminant use of other medicines
quality of management
what is the INR which is aimed for in warfarin monitoring
2-3
types of bleeding complication on warfarin
Mild
- skin bruising
- epitaxes
- haematuria
Severe
- gastro-intestinal
- intraverebral
- significant drop in Hb
how do you reverse the action of warfarin in bleeding
No action - if INR is normal and mild bleeding
omit some doses - if INR high and some mild bleeding
if INR high and not going down - administer oral vitamin K (takes about 6 hours for INR to come back down)
If major severe bleeding - administer clotting factors
why dont you give clotting factors immediately
risk of infection (blood product)
expensive
how quickly do vitamin k and clotting factors work
vit K - 6 hours
clotting factors - immediate
where do clotting factors bind to to form the fibrin clot
surface of platelets in the platelet plug
what do new anticoagulants target
Thrombin inhibitors (dabigatran) - directly inhibits thrombin (not through antithrombin like heparin)
Xa inhibitors (edoxaban, rivaroxiban, apixaban) - oral and dont need as much monitoring
why are new anticoagulants better
less monitoring
oral
less risk of bleeding
less drug interactions
dont effect protein C and S so can go straight onto them
what are new anticoagulants used for
prophylaxis for hip and knee replacement surgery
used for treatment of DVT/PE
Introduced for stroke prevention in Atrial Fib
