Anticoagulants, antithrombotics, and thrombolytics Flashcards
What is the purpose of anticoagulant drugs?
Slow clotting time and stop coagualtion cascade
Which anticoagulants are used for rapid termination of clot propagation? How are these administered?
Heparin, LMWH, and fondaparinux
Which anticoagulants would be used for a slow and prolonged effect?
Warfarin (Coumadin)
What would antiplatelet drugs be used for?
Inhibition of platelet activation and aggregation
What does aspririn do?
Inhibits produciton of thromboxane inhibiting platelet activation
What are clopidogrel, ticlodipine, prasugrel?
Inhibits the ADP receptor
What is cilostazol?
Inhibits platelet aggregation and stimulates vasodilation
What are abciximan, eptifibatide, and tirofiban?
Blockers of the GpIIb-IIIa complex
Whare are fibrinolytic drugs? What are two examples?
these are given to cause thrombolysis
t-PA and urokinase
Where is heparin isolated from?
Procine intestinal mucosa or bovine lung
What are the effects of heparin?
Heparin serves as a template for the binding of ATIII to thrombin
Also inhibits IXa, Xa, XIa, XIIa, and kalikrein
What are the effects of heparin on clotting times?
Prolongs aPTT and TT
Only high concentrations will prolong PT
How can heparin be administered and why?
Heparin is a large molecule which will be digested in the GI tract. It must be administered parenterally
How does the onset of action of heparin determine administration?
Heparin’s onset is directly related to the rate at which it appears in the blood. When rapid onset is required, an IV bolus with continuous IV perfusion is administered. When slower onset is sufficient, a subcutaneous injection is administered.
What is the process of a continuous heparin infusion?
Continuous infusion is initiated and then the bolus is given. Rate of infusion is adjusted base on aPTT. Although this allows rapid onset, hypervolemia may occur.
Why is intermittent intravenous heparin not recommended??
Can result in fluctuations of blood concentrations
What is normal aPTT time for heparin thearapy?
1.5-2.5
What are the two major manifestations of heparin toxicity?
Hemorrhage or HIT-1 and HIT-2
HIT-1 is a transient thrombocytopenia which normally resolves
HIT-2 is the formation of autoantibodies to the platelet factor-4 heparin complex. this causes thrombocytopenia, but immune complex damage of the endothelium will cause a prothrombotic state.
What are five indications for heparin use?
AMI, unstable angina, PE, DVT, or DIC
How do you treat heparin toxicity?
Immediate withdrawal of heparin and IV administration of protamine sulfate
Note: cannot reverse the effects of warfarin
What is protamine sulfate?
Protamine sulfate is a strongly negative protein which complexes and inactivates the strongly positive heparin protein
What are potential side effects (3) of protamine sulfate?
transient hypotension, thrombotic state, or anaphylaxis
What is the prototype of LMWH and its suffic
Enoxoparin
suffix = parin
What is the effect of LMWH?
LMWH has a greater affinity for Xa specifically over all others
What are the benefits of LMWH affinity?
It allows less frequent dosing reducing the risk of side effects
What are the indications (5) for LMWH?
Used to prevent DVT and thromboembolic events in abdominal surgery, hip replacement, knee replacement, and severe immobility
How does LMWH home therapy work?
pre-filled syringes are provided to the patient
What is Fondaparinux?
This is a synthetic analog of heparin, which inhibits Xa and not thrombin or platelet activity
What is the route of administration and benefits (3) of fondaparinux?
Administered subcutaneously
No HIT
does not prolong aPTT, PT, or bleeding time
Doesn’t affect platelet function
What are the indications for fondaparinux?
DVT, knee replacement, hip replacement, abdominal surgery, and immobility
What is hirudin and lepirudin? What are the uses? How is lepirudin administered?
Hirudin and lipirudin are irreversible thrombin inhibitors
Hirudin is produced by medicinal leeches and lipirudin is the recombinant form.
used to treat thrombosis in HIT
Administered by IV
What is argatrobin?
It is a reversible thrombin inhibitor used for HIT patients
What is warfarin?
It is an oral anticoagulant which interferes with the vitamin K-dependent coagulation factors. Inhibits II, VII, IX, X, PrS, PrC, and PrZ
What is the onset, absorption, bioavailability, duration of action, and termination of warfarin?
Onset is 36 to 72 hours. Completely absorbed through the GI mucosa and 99% bound to albumin. The duration of action is long because the termination half-life is 40 hours.
What are the toxic manifestations (4) and contraindication of warfarin?
Toxicity - hemorrhage, anorexia, nausea, vomiting, and diarrhea
Contraindication - pregnancy
What is warfarin used for?
Prophylaxis in any condition increasing thromboemboli
How is warfarin therapy monitored?
Monitored by INR with PT time. Normal INR is 2-3
How do you treat warfarin toxicity?
Withdrawal of warfarin, administration of vitamin K, and possibly frozen plasma rich in II, VII, X
What is dabigatran etexilate?
This is an orally administered thrombin innhibitor which also reduces the thrombin activation of platelet aggregation. It is rapidly absorbed as a prodrug and converted in the blood by esterases.
Note: has a less variably effect compared to warfarin and doesn’t require INR monitoring.
What is rivaroxaban?
An orally administered factor Xa inhibitor which seems more effective than LMWH
How does aspirin act as an antiplatelet agent?
aspirin is an irreversible COX-1 inhibitor which blocks the production of thromboxane-2.
What are the indications for aspirin in CVD?
primary prevention of MI and secodary prevention of MI
What is clopidogrel?
This is an orally administered drug which irreversibly inhibits the ADP receptor on platelets and subsequently the ADP-dependent activation of the gpIIb-gpIIIa complex. Administered as a prodrug.
What are the indications (4) of clopidogrel?
prophylaxis of stroke, MI, PAD, and ACS
What is the mechanism of action, indication, and adverse effects (2) of ticlodipine?
Irreversible blocks the binding of ADP and fibrinogen to platelets. Used to prevent stroke and TIA. Can cause TTP and aplastic anemia.
What is cilostazol? what is the mechanism of action? What is the indication? what is the contraindication?
Cilostazol is an inhibitor of cAMP PDE-III. Increases the concentration of cAMP in blood vessels causing vasodilation and inhibition of platelet aggregation.
Used for intermittent claudication. contraindicated in CHF
What is dipyridamole? What are its three indications?
It is a PDE inhibitor which raises cAMP levels.
Used for secondary prevention of AMI in prosthetic valve patients. Prevention of stroke in TIA. Maintenance of valve patency in coronary bypass graft.
What is abciximab? Its mechanism of action? Indications (2)?
Abciximab is a monoclonal antibody which inhibits gpIIb-IIIa inhibiting platelet aggregation. Used for high risk angioplasty and ACS.
What is pentoxyifylline?
This drug increases the flexibility of erythrocytes and decreased blood viscosity. Used for intermittent claudication.
Name three thrombolytics?
t-PA (alteplase, reteplase, and tenecteplase), streptokinase, urokinase
What are the 4 indications for thrombolytics?
AMI, PE, DVT, and stroke
What is significant about the blood interactions of streptokinase?
Many patients have developed antibodies, so a loading dose must be given to saturate these sites.
What are the uses of aPTT (4)?
monitor intrinsic pathway, hemophilias A and B (factor VIII and IX deficiency), and unfractionated heparin therapy.
