BL- Antithrombotic drugs Flashcards
interfere with the coagulation cascade and prevent thrombin formation.
Heparin and oral anticoagula
fibrinolytin–> thrombin–> fibrin
They lyse clots by increasing formation of plasmin
Fibrinolytic agents
fibrin–> plasmin–>degrade product
inhibit formation of platelet products or
block platelet adhesion preventing platelet aggregation and clot formation
. Anti-platelet agents.
Proteoglycan with sulfated polysaccharides of varying lengths (~12,000 daltons). Made from pig intestine.
Unfractionated Heparin
Depolymerized heparin- (~4500 daltons).
Better pharmkintetics
Low Molecular Weight Heparin (LMWH).
Synthetic pentasaccharide (5) corresponding to the minimal sequence in heparin for binding anti-thrombin.
Fondaparinux. (type of heprin)
binds antithromin 3
Examples of pathologic thrombi formation
Formation of thrombus in atrial fibrillation
Formation of deep vein thrombus (DVT)
Formation of thrombus on atherosclerotic plaque
Fibrin
required for a stable clot
Three types of heprin
Unfractionated Heparin
Low Molecular Weight Heparin (LMWH)
Fondaparinux
Current Heprin Concerns
shortage- sourced by China
contamintaion- chondroitin sulfate
What does Heprin bind?
Antithrombin 3
How does heprin work
helps antithromin 3 inactivate coag factors
______dependent differences in action of heparins
Size
Unfractionted heprin binds
AT-3
2a
10a
Low molecular weight heprin (LMWH ) binds
AT-3
10a
Unfractionted heprin route/pharmkinetics
IV or Sub-Q
Does not cross placenta
Unpredictable dose response
Requires hospital admission and monitoring.
LMWH and fondaparinux route/pharmkinetics
Administered sub-cutaneously
Better bioavailability, more predictable dose response, longer half-life
Less monitoring (outpatient)
Uses of Heparins
Coronary angioplasty
stent placement
Surgery requiring cardiopulmonary bypass
Kidney dialysis
Uses of Heparins
*Used with warfarin
Venous thrombosis, pulmonary embolism (heparins act rapidly)
(Abdominal surgery, hip and knee replacement)
Uses of Heparins
✪Used with fibrinolytics
myocardial infarction✪
Toxicity of Heparins
- Bleeding
- Heparin-induced thrombocytopenia
- Allergic Reaction
a. Discontinue drug
b. Effects are reversed with protamine sulfate.
Toxicity of Heparins
Bleeding
Oral Anticoagulants
Warfarin
Pharmacokinetics of Warfarin
Rapidly absorbed
Good bioavailability
Long half-life
Slow onset of action
Warfarin Used to prevent
Venous thromboembolism (used with heparin)
Embolism in patients with prosthetic valves or atrial fibrillation
Stroke, recurrent infarctions
a. Low platelet count due to production of AB to plt factor 4/heparin complexes. ABs bind to plts and induce a pro-thrombotic state.
b. Less common with LMWH and fondaparinux
c. Direct thrombin inhibitors used as anti-coagulants Argatroban, Lepirudin
Heparin-induced thrombocytopenia
Warfarin: Adverse effects and problems
Hemorrhage- administer vit. K/plasma
Crosses placenta - teratogenic
Drug interactions/food
Delayed onset of action
Requires monitoring
Dicumarol
precursor of warfrin
Warfrin is a _____ antagonist
Vit.K
a. Due to the contaminant oversulfated chondroitin sulfate
b. Activation of the contact system (bradykinin, complement)
Allergic Reaction to heprin
New oral anticoagulants
Direct thrombin or Factor Xa inhibitors
Direct thrombin or Factor Xa inhibitors Advantages
Rapid onset of action
Absence of food interactions
Do not require monitoring
Direct thrombin or Factor Xa inhibitors
Disadvantages
*Contraindicated with kidney disease Greater GI bleeding than with warfarin Short half-life Cost (20X> warfarin) **No antidote to reverse effects
Oral prodrug, a potent direct thrombin inhibitor
Lower rates of stroke and systemic embolism than with warfarin
Less intracranial hemorrhage (but increase in MI)
No antidote available to reverse its effects
Dabigatran etexilate (Pradaxa) for afib/VTE
Direct inhibitors of Factor Xa
Superior to warfarin in preventing strokes and emboli for treatment of atrial fibrillation
Apixaban (Eliquis), FDA approved for afib
Rivaroxaban (Xarelto), FDA approved in 2011 for afib/VTE
Dabigatran etexilate (Pradaxa) for afib/VTE
Oral prodrug, a potent direct thrombin inhibitor
Lower rates of stroke and systemic embolism than with warfarin
Less intracranial hemorrhage
INC in MI
No antidote available to reverse its effects
Apixaban (Eliquis), FDA approved for afib
Rivaroxaban (Xarelto), FDA approved in 2011 for afib/VTE
Direct inhibitors of Factor Xa
Superior to warfarin in preventing strokes and emboli for treatment of atrial fibrillation
Tissue plasminogen activator
Serine protease
convert plasminogn to plasmin
plasmin degrades fibrin
(desolves clot)
Uses of Fibrinolytic drugs
ER rx for:
acute myocardial infarction
Ischemic stroke
Deep vein thrombosis and pulmonary embolism
Adverse effects of Fibrinolytic drugs
Hemorrhage from lysis of “physiological clots”
Induce a systemic lytic state due t increased plasmin formation
Inhibits thromboxane A2 production by irreversibly inactivating cyclooxygenase 1.
Anti-platelet Drugs
Aspirin
Aspirin uses
after AMI and thrombotic stroke (with thrombolytics) to prevent AMI and stroke in high-risk patients
Anti-platelet Drugs
ADP receptor blockers
Clopidogrel (PLAVIX)
Ticagrelor
Bind IRREVERSIBLY to ADP receptor.
Block alpha granule secretion and expression of adhesion proteins, GPIIb/IIIa
Slow onset of action
Used to prevent AMI and thrombotic stroke (with aspirin)
Clopidogrel- PLAVIX
Binds REVERSIBLY to ADP receptor
Acts more rapidly
Ticagrelor
block binding of fibrinogen to
the adhesion protein GPIIb/IIIa.
Anti-platelet Drugs
Glycoprotein IIb/IIIa inhibitors
