Anticoagulants Flashcards
How does aspirin work as an anticoagulant?
It inhibits platelet aggregation but irreversible acetylating COX1 which blocks the synthesis of TXA2 (a promoter of platelet aggregation).
It also blocks PGI2 (an inhibitor of platelet aggregation) but PGI2 comes from endothelial cells which can synthesize more. TXA2 comes from platelets which don’t have nuclei to synthesize more.
How is aspirin administered?
What dose achieves maximum antithrombotic effect?
Orally- rapid action 2hrs.
80-325mg
What are the adverse effects of using aspirin?
- Hemorrhage- a single dose of aspirin increases the bleeding risk for 4-7 days
- GI ulcers (rare at 80-325mg) in ppl on steroids
- ASA intoxication
Aspirin use is contraindicated in what 4 patients?
- severe hepatic damage
- hypoprothrombinemia
- vit K deficient
- hemophilia
Basically people that were already at an increased bleeding risk
What are the 4 therapeutic uses of aspirin?
- prevent a stroke in patients with transient ischemic attack
- prevent occlusive cardiovascular diseas in patients with MI or unstable angina
- increase saphenous vein patency in bypass grafts
- prophylaxis in patients at risk for a myocardial infarction
What age should women start taking aspirin prophylactically to decrease risk of MI?
Men?
Why not younger?
Women- 55
Men- 45
If they were younger the benefit would be offset by the increased risk of hemorrhagic stroke
What is the mechanism of clopidogrel?
It inhibits platelet ADP receptors which prevents activation of GpIIb/IIIa.
This reduces:
- fibrinogen and vWF binding
- platelet aggregation
- clot retraction.
Describe the pharmacokinetics of clopidogrel. Administration Mechanism Time of onset Duration
It is an orally administered prodrug that becomes converted to metabolites by hepatic cyp metabolism.
The metabolites irreversible bind ADP receptors which prevent GpIIb/IIIa activation.
Onset is slow (several days) because it needs to be converted before action
It has prolonged action after discontinuation
What are the adverse effects of clopidogrel?
rashes, diarrhea, neutropenia, bleeding
What are the therapeutic uses of clopidogrel?
- Reduce MI, stroke, vascular deaths in patients with coronary syndrome
- reduce stint occlusion
What is the mechanism of GpIIb/IIIa blockers?
How are they administered?
What is their major adverse effect?
They inhibit:
- fibrinogen and vWF binding
- prevent clot retraction
- block platelet binding in the presence of agonists like ADP, TXA2, thrombin and collagen)
They are administered IV with:
- Heparin and ASA
- clopidogrel
They can cause bleeding
What are the two main reasons to use anticoagulant drugs?`
How do they achieve their purpose?
- to reduce risk of thrombosis or embolism
- to prevent extension of current venous thrombus
They block coagulation cascade. They cannot dissolve an existing thrombus but can prevent extension of the thrombus and block formation of new thrombi.
What are the four major mechanisms of thrombin?
- Fibrinogen–> fibrin
- activate factors 5 and 8
- activate factor 11
- activate factor 13
What is the mechanism of Heparin?.
It is a sulfated mucopolysaccharide with an electronegative charge that interacts with antithrombin III to increase the ability of ATIII to neutralize factor Xa and thrombin.
What coagulation factors does thrombin affect?
Factor Xa and thrombin (ACTIVATED FACTORS)
It has no effect on factor X or prothrombin, the inactive precursors
What is LMWH? How is its action different from that of heparin?
Low molecular weight heparin is hydrolyzed heparin that has a MW of 4-5 kDalton instead of 15.
Like heparin, LMWH binds to antithrombin III to enhance its effects.
The difference is that LMWH and fondaparinux bind ATIII and inactivate Xa but they have little effect on thrombin.
How must heparin, LMWH and fondaparinux be administered?
How frequently are they administered?
They have an electronegative charge and are large so they can’t be absorbed in the GI.
They are administered SC or IV.
Heparin IV is repeated every 4-8 hours
LMWH is SC every 12-24 hours
What is the difference in IV heparin administration and SC administration?
IV is immediate
SC is delayed 20-60 minutes
What are the two general adverse reactions to heparin or LMWH?
- Hemorrhage
2. Thrombocytopenia
What is the incidence of serious bleeding when given:
- heparin
- LMWH
- fondaparinux
How can bleeding by heparin or LMWH be reversed?
- 1-4%
- 1-3%
- 1-2%
Bleeding is reversed with protamine sulfate which is positively charged and binds the electronegative heparin molecule. NO reversal for fondaparinux.
Who would the use of heparin be contraindicated in?
- recent brain or eye surgery
- thrombocytopenia
- uremia
- history of bleeding
- on current platelet inhibitor
What causes HIT?
How can it be prevented?
Heparin induced thrombocytopenia is caused by the generation of heparin-dependent antibodies.
The antibodies cause platelet activation, thrombocytopenia, and thrombosis.
There are screening methods to detect the presence of heparin-dependent antibodies.
What are the therapeutic uses of heparin?
- venous thrombosis and PE, manage MI, angina, during/after coronary angioplasty or stent placement, cardiopulmonary bypass surgery
- Prevention/treatment of venous thromboembolism in hip-replacement patients
- Anti-coagulation during pregnancy
What is warfarin? What is the method of action?
Super warfarin is rat poison that causes internal bleeding and death in rats
Warfarin is an antagonist to Vitamin K which inhibits the synthesis of coagulation factors 2,7,9,10 in the liver. (it also inhibits the anti-coagulants protein C and S)
