Flashcards in 6: Anticoagulants, Thrombolytics, Antiplatelet agents & Antifinrinolytics Deck (44):
What are Anticoagulants?
Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of thrombi.
What rae Thrombolytics/Fibrinolytic's?
Substances that promote the destruction of already formed blood clots or thrombi (i.e lyse thrombi) by disrupting the fibrin mesh
What are Anti platelets?
Drugs that reduce the adhesion and aggregation of platelets
What are Antifibrinolytics?
Drugs that promote the formation of clots and prevent excessive bleeding
What do Anticoagulants inhibit?
The action or formation of one or more of the clotting factors
Why should Anticoagulants be treated with caution?
They create an immediate defect (minutes when given IV, hours when given orally) in the clotting mechanism and should be treated with caution.
What is the range between sufficient therapy and hemorrhagic risk?
The risk is narrow and varies considerably from patient to patient.
-A large # of unrelated drugs also affect the dose of the anticoagulant needed to produce a desired effect.
-Individual treatment & frequency lab tests are imperative.
What are the Anticoagulants be divided into?
1) Indirect Thrombin Inhibitors (basically HEPARIN :)
2) Coumarin Anticoagulants (basically WARFARIN)
3) Direct THROMBIN INHIBITORS
4) DIRECT FACTOR X INHIBITORS
What is Heparin ?
Commercial heparin is actually a mixture of heparins (protein molecules) w/ a wide range of molecular weights
What are the 2 MOST common preparations:
1) Unfractionated heparin (UFH)--Heparin Sodium
2) Low-molecular-wt heparin (LMWH)-- Fragmin, Innohep, Lovenox
How does Heparin work ?
Heparin stimulates Antithrombin III (this neutralizes the activity of factor & other factors)
What occurs to the intrinsic system without factor Xa?
Prothrombin can't be converted into thrombin, which ultimately prevents FIBRIN formation from FIBRINOGEN
Why is Heparin called an "indirect thrombin inhibitor" ?
Stimulates heparin cofactor II which inhibits thrombin
What is Unfractionated Heparin (UFH)
****Effective parenteral ANTICOAGULANT for the PREVENTION of clots!
-Discovered in 1916 and has been used for more than 50 years
Why is Unfractionated Heparin (UFH) not effective if given orally?
Not absorbed if given orally as heparin proteins are destroyed by stomach acidity.
***Given by IV (bolus or infusion)
When UFH binds to a number of plasma proteins (or endothelial cells & macrophages) what happens?
It reduces its anticoagulation activity & causes a rather larger variability of anticoagulant response among patients.
***The relationship between UFH dose & UFH response is a bit tricky
Since the anti-coagulant response to UFH varies among patients what is it important to do?
It is standard practice to adjust the dose of UFH & monitor its clinical effectiveness w/ the activated partial thromboplastin time (APTT)
What is the normal APTT time?
**Therapeutic levels of UFH will typically prolong the aPTT (activated partial thromboplastin time) to 2-2.5 times that of the normal value
How can LMWH preparations be used?
In-hospital or out-of-hospital setting b/c they can be administered SC(typically w/ pre-filled needle/syringe systems) on a body weight basis w/out the needle for lab monitoring
What is the only major coumarin anticoagulant in the US?
****Can lead to death by hemorrhage or internal bleeding
How does Warfarin work?
Inhibits blood clotting mechanisms by interfering w/ the hepatic synthesis of the VITAMIN K DEPENDENT CLOTTING FACTORS (2, 7, 9, 10)
What is the long-term treatment or prophylaxis of Warfarin?
1) Venous thrombosis
*Post-MI and post-op (after cardiac, vascular surgery) patients. Prevention of systemic thromboembolism in patients w/ prosthetic heat valves or atrial fibrillation
What is INR?
The therapeutic range for oral anticoagulation therapy is defined in terms of the international normalized ration (INR)
*****Therapeutic levels of warfarin should be adjusted to achieve an INR of 2.0-3.0
What are the Key Drug-Drug Interactions Warfarin that inhibit warfarin metabolism(inhibit breakdown) ?
These inhibit warfarin metabolism:
1) Cimetidine (Tagamet) --acid reflux
2) Acetaminophen (Tylenol)
3) High dose, acute alcohol
***Keeps it around in the blood longer :)
What are the Key Drug-Drug Antibiotic Interactions that inhibit warfarin metabolism (inhibiting its breakdown)?
1) Azithromycin (Zithromax)
***INR goes up!! (when inhibited) and can lead to bleeding.
(Sticks around a lot long and accumulated in the body)
How can synthetic thyroid hormones affect the catabolism of many clotting factors & can potentiate the effects of warfarin?
INCREASE ( inhibit the anticoagulant action-blood clots)
Which Drugs stimulate WARFARIN metabolism (breaking it down fast) and may diminish the desired effects?
1) Chronic alcohol use
2) Phenytonin (Dilantin) --seizure meds
***Oral contraceptives INCREASE the synthesis of many factors and can reduce the effects of warfarin (causes blood clots)
Note: Rhis DECREASES the INR !!
What does interactions involving warfarin & food rich in vitamin K result in?
DECREASED warfarin effects by stimulating the synthesis of vitamin K dependent clotting factors.
***Often b/c of leafy vegetables (maintain consistent daily intake)
What are Warfarin overdoses typically treated by?
With vitamin K & transfusion
What are the side effects of Warfarin?
Bleeding is most common side effect. Occurs most often from the mucous membranes of the GI tract & the genitourinary tract.
Why is Warfarin contraindicated during pregnancy (Category X) ?
Should not be used during pregnancy b/c it crosses the placenta & is teratogenic.
***Breast feeding should also be avoided during warfarin therapy!!
What are the Direct Thrombin Inhibitors?
Example: Dabigatran (Pradaxa) 1st orally direct thrombin inhibitor!!!
If offers an alternative to warfarin as an orally administered anticoagulant.
**This NEW drug does not require frequent blood tests for INR, doesn't affect vitamin K or antibiotic levels :) :)
What is an example of a DIRECT FACTOR X INHIBITORS?
(newly release in 2011)
What are Thrombolytics/Fibrinolytics?
Rapidly lyse thrombi when administered intravenously by catalyzing the formation of plasmin from plasminogen
**Bust clot to regulate regular blood flow
What are examples of Thrombolytics/Fibrinolytics?
3) Synthetic tPA
Why would you administer Thrombolytics/Fibrinolytics?
For acute Mi, acute ischemic stroke and PE.
***for best results, Thrombolytics work best the sooner they are initiated from the onset of the event.
What are the main classes of Antiplatelet agents?
1) Cyclooxygenase Inhibitors( aspirin)
2) Thienopyridines (ADP Inhibitors)
3) GP IIb/IIIa inhibitors
How does Aspirin act on platelets?
By inhibiting the synthesis of TXA2 one of the substances that helps make the platelets sticky & more likely to aggregate
What are the Thienopyridines (ADP Inhibitors?)
Prevent the binding of ADP to its receptor on platelets, thereby inhibiting an important pathway that leads to platelet aggregation.
What is the main drug that fits in this category ( Thienopyridines (ADP Inhibitors?)
or new one Effient (ADP inhibitor)
What are GP IIb/IIIa inhibitors?
These inhibit the activation of glycoproteins IIb/IIIa receptors on platelets, inhibiting the "final common pathway" for platelet aggregation
What is an example of a drug that is an GP IIb/IIIa inhibitors?
**Administered IV w/ an initial bolus followed by constant infusion
What are Antifibrinolytics? What is an example?
Inhibits the activation of plasminogen to plasmin
(***Counteracts the Tissue plasminogen activator tPA)
Example= Tranexamic acid (reduce clots from being dissolved, keep them around longer)