Antithrombotics Flashcards
Thrombus
A clot that adheres to the wall of a blood vessel
Embolus
A clot that has dislodged from the vessel wall and is freely moving in the blood stream
What is the difference between an arterial and venous thrombus
Arterial is usually due to a collection of platelets. Where as a venous clot usually forms because of inappropriate activation of the coagulation cascade (rich in fibrin)
What is the MOA of anti-platelet therapies
Prevents platelets from aggregating by inhibiting the COX-1 enzyme (cox-1 is cyclooxgenase)
Which NSAID is the only one that irreversibly exhibits antithrombotic efficacy
Aspirin (also has a 7-10 half life)
What are anti platelet drugs used for
Treatment of MI and stroke (arterial clot prevention)
What is the MOA of anticoagulation
Either inhibits the action of the coagulation factors (thrombin inhibitors) or inhibits the synthesis of coagulation factors (vitamin K antagonists)
What is the extrinsic clotting system triggered by
Factor VII
What is the intrinsic clotting system triggered by
Factor XII
What are the steps of blood clot (clotting cascade - basic end pathyway)
Factor Xa initiates the conversion of prothrombin to thrombin. Thrombin then activates fibrinogen to fibrin formation which becomes the blood clot
Which pathway can you test PTT for
Intrinsic
Which pathway can you test pT for
Extrinsic
What drug works on the intrinsic pathway (pTT)
Heparin
What drug works on the extrinsic pathway
Warfarin
Which drug is a thrombin inhibitor
heparin
Which drug is a vitamin K antagonist
warfarin
What is the MOA of the antithrombin drugs
Blocks the prothrombin/thrombin interaction in the clotting cascade (interferes with formation of thrombi)
What is the MOA of the Vitamin K antagonists
Protein coagulation factors need vitamin K as a cofactor. By blocking vitamin K, it results in clotting factors with diminished activity (prevents clot from getting bigger)
What is a major difference of heparin and warfarin
Takes a lot longer for warfarin to work 8-12 hours, but peak effects may be even as late as 72 hrs.
How to you reverse the effects of coumadin
give vitamin K
What are anticoagulation drugs used for
prevention of venous thromboembolism, DVT, PE
What is the MOA of thrombolytic agents
Act directly or indirectly to cover plasminogen to plasmin, which cleaves fibrin (lyses clot = fibrinolysis)
What are the adverse effects of coumadin
- Hemorrhage
2. Numerous drug drug interactions due to liver metabolism (aspirin, alcohol, metronidazole)
How do you monitor coumadin
INR 2-3 is therapeutic window, or pT test
What additional clinical uses does heparin have
- surgical prophylaxis
2. Pregnant women with prosthetic heart valves or DVT/PE, do not cross placenta
Administration of heparin
Must be given parenterally - IV (1-2 hours) - NO IM INJECTIONS. Due to potential hemorrhagic issues
Administration of warfarin
Given orally. 99% bound which prevents diffusion into CSF, urine or breast milk. Crosses the placenta.
What is the absorption of LMWH
Subcutaneous injection that takes 4 hours to get max effect.
What are the adverse effects of heparin
- Bleeding
2 Hypersensitivity - Thrombocytopenia
- abnormal LFT
MOA of dabigatran (Pradaxa)
Antithrombotic (anticoagulant)
What is the use of dabigatran
Prodrug that is a direct thrombin inhibitor used for prevention of stroke and systemic embolism with atrial fibrillation.
How is dabigatran administered
Orally, very few side effects, does not need to be monitored
MOA of rivaroxaban (xarelto)
Antithrombotic (anticoagulant)
What is the use of rivaroxaban
DVT, afib in nonvalvular patients
What is the MOA of aspirin
it is an anti platelet drug. Which means that it inhibits platelet aggregation factors (COX 1). And more specifically in aspirin thromboxane A2 is inhibited
What is aspirin used for
MI, stoke (transient cerebral ischemia)
Adverse effects of aspirin
- Bleeding
- Increased risk for hemorrhagic stroke
- GI bleeding
MOA of ticlopidine (ticlid)
Anti platelet aggregation but different mechanism than aspirin. Blocks ADP from binding to receptors which then inhibits platelets to bind to fibrinogen and to each other
What is ticlopidine used for
Prevention of transient ischemic attacks and strokes for patients with prior cerebral thrombotic events. Also used during coronary stent placement to decrease risk of clot forming on the stent.
Adverse effects of ticlopidine
- Neutropenia/agranulocytosis
- Thrombotic thrombocytopenia purpura *TTP
- Aplastic anemia
MOA of copidogrel (plavix)
Anti platelet, same mechanism as ticlopidine
What is the use of clopidogrel
Prevention of atherosclerotic events following recent MI, stroke, or established peripheral arterial disease. Also used for with coronary stent procedures (used more in heart patients than in ticlopidine)
Adverse effects of clopidogrel
Better adverse effects than ticlopidine. Still can cause TTP.
MOA of dipyridamole (persantine)
Antiplatelet mechanism. Increases cellular levels of cAMP which results in decreased thromboxane A2 synthesis
What is thromboxane A2 responsible for
Promotes clumping process of platelets
What is dipyridamole (persantine) used for
- Coronary vasodilator - given to patients with artificial heart valves
- Usually given in combo with aspirin/or warfarin
Adverse effects of dipyridamole
- GI bleeding
- should not be used in elderly
- Orthostasis problems
MOA of alteplase (tPA, activate)
Low affinity for free plasminogen but rapidly activates plasminogen that is bound to fibrin in a clot or hemostatic plug. “fibrin selective”
Use of alteplase
MI, massive PE, acute ischemic strokes
Adverse effects of alteplase
- Major bleeding complications
- GI bleeding
- Cerebral hemorrhage
MOA of Urokinase (abbokinase)
Directly cleaves arganine-valine bond of plasminogen to yield active plasmin
Use of urokinase
Only approved for lysis of PE.
off label use - acute MI, arterial thromboembolism, coronary thrombosis and DVT
Adverse effects of urokinase
Bleeding
