Anticoagulants and thrombolytics Flashcards
What is the mechanism of action of warfarin?
Inhibits vitamin k reductase which means that tissue factor cannot be carboxylated.
acts in liver.
What is the t0.5 of warfarin?
40 hrs
What is warfarins measurement of action?
INR (a measure of prothrombin time)
Where is warfarin metabolized?
Liver
Where does warfarin act?
liver
Why can aspirin cause increased effects of warfarin?
Aspirin displaces warfarin from plasma proteins
What other drugs potentiate the action of warfarin?
Sulphonamides - as they interfere with liver function
NSAIDS - as they interfere with platelet function
Decreased Vit K levels.
What drugs decrease the potency of warfarin?
- Barbituates, Vitamin K. colestipol.
Drugs which induce metabolizing enzymes
Increased vitamin K levels (promotes clotting factor synthesis)
Cholestipol (reduced warfarin absorption).
What are some advantages of DOACs over warfain?
Fixed dose
Predicatble
Quick onset and short t1/2 so easier initiation and perioperative management.
What are some cons of using DOACs compared to warfarin?
Need for good compliance as patient needs to take once a day.
Short t1/2 and no INR monitoring needed.
What is the mechanism of action of Heparin?
Activated antithrombin III leading to removal or thrombin/Xa.
What is the differences between LMWH and heparin?
LMWH can only remove factor X where as heparin can bind factor X and thrombin.
LMWH can only be subcutaneously administered compared to heparin which can be done by IV.
LMWH does not bind to plasma proteins.
When would we use Warfarin/heparin?
Prevention of DVT
Patients at risk of DVT
Treatment of DVT / prevention of pulmonary thrombi.
Heparin is used for short term acute treatment whilst warfarin / DOAC is administered for a more prolonged amount of time.
How can we reverse the effects of heparin and DOACs?
antidotes
How can we counteract the effects of warfarin?
Vitamin K
Vitamin K transfusion which in turn increases the amount of clotting factors that can be produced by the liver.
Also blood transfusion in order to replace clotting factors.
What are the properties of platelets and what is the function?
Small
Anuclear
Stick to damaged blood vessels and have a major role in both thrombosis and clot formation.
What can come from increased platelet activity?
Thrombosis - heart attack and stroke due to emboli blocking cerebral/cardiac arteries.
Describe the role of platelets in thrombosis
Platelets adhere to exposed collagen via von Willebrand factor.
Platelets secrete chemicals (thromboxane A2) which promote platelet aggregation.
This causes platelet crosslinking via fibrin.
Name two antiplatelet drugs?
Aspirin - inhibition of COX-1
Clopidogrel - bind to ADP receptor ( P2Y12)
Why does Aspirin selectively decrease the production of thromboxane A2 in platelets whilst not decreasing the production of PGI2 in endothelial cells?
Aspirin targets COX-1 in both cells, however platelets take between 7-10 days to replace COX where as endothelial cells can replace immediately so they can contiue to produce PGI2 where as TxA2 production stops as there is no COX enzymes in the platelets.
PGI2 is responsible for decreasing platelet activity where TXA2 is responsible for activating it.
Why is >1000mg of aspirin a day not beneficial for preventing heart attack/stroke?
Too much inhibition of endothelial cox so that it cant produce PGI2. - so no down regulation of platelet activty.
What is the outcome of ADP binding to the p2y12 receptor?
Platelet recruition.
Increased platelet aggregation
Increased coagulation activity.
Give an example of an irreverisbile p2y12 receptor antagonist?
Clopidogrel
Ticlopidine
Prasgrel
What is clopidogrel used for?
Preventing stroke and MI
What is the mechanism of action of abcimimab?
Antibody fragment which is used as an antagonist to aiibb3 receptor.
Prevents fibrin cross linking.
What are the clinical uses of drugs which reduce platelet activation? (clopidogrel, aspirin, abciximab)?
Predomiantly to prevent/treat arterial thrombosis.
Acute MI
In patients with risk of MI
Following coronary bypass
Following Coronary angioplasty
Thrombotic stroke.
What are some side effects of anti platelet activation drugs?
Gi distrubances/ indigestion
Bleeding - GI, Nose, brusing
Shortness of breath - trcagrelor specific.
How do we prescribe clopidogrel?
Oral administration
Name some fibrinolytic drugs?
Streptokinase
Alteplase
Urokinase
Anistreplase
What is the mechanism of action of streptokinase?
Forms complex with plasminogen to produce plasmin, which then goes to degradation of fibrin clot.
How long must you wait between using streptokinase?
1 year
Why does streptokinase action only last approx. 4 days?
Action is blocked by antistreptococcal antibodies after 4 days.
Why do we have to administer alteplase by IV infusion?
short half life
Why is alteplase seen to be more clot specific?
More activity at fibrin bound plasminogen.
What are the clinical uses of fibronlytics?
Acute MI - within 12 hours of onset.
Acute thrombotic stroke
Acute arterial thromboemolism (pulmonary emoblism).
What are some unwanted effects of fibrinolytics?
Gi heamorrhage
Haemorraghic Stroke
Low grade allergic reaction
Burst of plasmin caused by streptokinase can result in release of kinins which can cause hypotension.
When would we definitely not use fibrinolytic drugs?
Active or recent internal bleeding
Recent cerebrovascular accident
Invasive procedures where haemostasis is important.
Name two antifibrinolytic drugs
tranexamic acid
aprotinin
What is the mechanism of action of tranexamic acid?
inhibits plasminogen activator
What is the mechanism of action of aprotinin??
Breaks down plasmin.
How do we administer Tranexamic acid?
oral/iv
When would we use tranexamic acid?
reduce risk of bleeding
When increased risk of bleeding (dental extraction).
When do we use aprotinin?
High risk of blood loss during and after open heart surgery.
What drugs are used to treat venous thrombosis?
Warfarin
Heparin
Name some NOACs which act by inhibiting factor X?
Rivaroxaban
Edoxaban
Apixaban
what NOAC is a direct thrombin inhibitor?
Dabigatran
