BL- Antithrombotic drugs

Question 1

interfere with the coagulation cascade and prevent thrombin formation.

Answer 1

Heparin and oral anticoagula

fibrinolytin–> thrombin–> fibrin

Question 2

They lyse clots by increasing formation of plasmin

Answer 2

Fibrinolytic agents

fibrin–> plasmin–>degrade product

Question 3

inhibit formation of platelet products or

block platelet adhesion preventing platelet aggregation and clot formation

Answer 3

. Anti-platelet agents.

Question 4

Proteoglycan with sulfated polysaccharides of varying lengths (~12,000 daltons). Made from pig intestine.

Answer 4

Unfractionated Heparin

Question 5

Depolymerized heparin- (~4500 daltons).

Better pharmkintetics

Answer 5

Low Molecular Weight Heparin (LMWH).

Question 6

Synthetic pentasaccharide (5) corresponding to the minimal sequence in heparin for binding anti-thrombin.

Answer 6

Fondaparinux. (type of heprin)

binds antithromin 3

Question 7

Examples of pathologic thrombi formation

Answer 7

Formation of thrombus in atrial fibrillation

Formation of deep vein thrombus (DVT)

Formation of thrombus on atherosclerotic plaque

Question 8

Fibrin

Answer 8

required for a stable clot

Question 9

Three types of heprin

Answer 9

Unfractionated Heparin
Low Molecular Weight Heparin (LMWH)
Fondaparinux

Question 10

Current Heprin Concerns

Answer 10

shortage- sourced by China

contamintaion- chondroitin sulfate

Question 11

What does Heprin bind?

Answer 11

Antithrombin 3

Question 12

How does heprin work

Answer 12

helps antithromin 3 inactivate coag factors

Question 13

______dependent differences in action of heparins

Answer 13

Size

Question 14

Unfractionted heprin binds

Answer 14

AT-3
2a
10a

Question 15

Low molecular weight heprin (LMWH ) binds

Answer 15

AT-3

10a

Question 16

Unfractionted heprin route/pharmkinetics

Answer 16

IV or Sub-Q
Does not cross placenta
Unpredictable dose response
Requires hospital admission and monitoring.

Question 17

LMWH and fondaparinux route/pharmkinetics

Answer 17

Administered sub-cutaneously

Better bioavailability, more predictable dose response, longer half-life

Less monitoring (outpatient)

Question 18

Uses of Heparins

Answer 18

Coronary angioplasty
stent placement
Surgery requiring cardiopulmonary bypass
Kidney dialysis

Question 19

Uses of Heparins

*Used with warfarin

Answer 19

Venous thrombosis, pulmonary embolism (heparins act rapidly)
(Abdominal surgery, hip and knee replacement)

Question 20

Uses of Heparins

✪Used with fibrinolytics

Answer 20

myocardial infarction✪

Question 21

Toxicity of Heparins

Answer 21

1. Bleeding
2. Heparin-induced thrombocytopenia
3. Allergic Reaction

Question 22

a. Discontinue drug

b. Effects are reversed with protamine sulfate.

Answer 22

Toxicity of Heparins

Bleeding

Question 23

Oral Anticoagulants

Answer 23

Warfarin

Question 24

Pharmacokinetics of Warfarin

Answer 24

Rapidly absorbed
Good bioavailability
Long half-life
Slow onset of action

Question 25

Warfarin Used to prevent

Answer 25

Venous thromboembolism (used with heparin) Embolism in patients with prosthetic valves or atrial fibrillation Stroke, recurrent infarctions

Question 26

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

Answer 26

Heparin-induced thrombocytopenia

Question 27

Warfarin: Adverse effects and problems

Answer 27

Hemorrhage- administer vit. K/plasma Crosses placenta - teratogenic Drug interactions/food Delayed onset of action Requires monitoring

Question 28

Dicumarol

Answer 28

precursor of warfrin

Question 29

Warfrin is a _____ antagonist

Answer 29

Vit.K

Question 30

a. Due to the contaminant oversulfated chondroitin sulfate | b. Activation of the contact system (bradykinin, complement)

Answer 30

Allergic Reaction to heprin

Question 31

New oral anticoagulants

Answer 31

Direct thrombin or Factor Xa inhibitors

Question 32

Direct thrombin or Factor Xa inhibitors Advantages

Answer 32

Rapid onset of action Absence of food interactions Do not require monitoring

Question 33

Direct thrombin or Factor Xa inhibitors | Disadvantages

Answer 33

``` *Contraindicated with kidney disease Greater GI bleeding than with warfarin Short half-life Cost (20X> warfarin) **No antidote to reverse effects ```

Question 34

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

Answer 34

Dabigatran etexilate (Pradaxa) for afib/VTE

Question 35

Direct inhibitors of Factor Xa | Superior to warfarin in preventing strokes and emboli for treatment of atrial fibrillation

Answer 35

Apixaban (Eliquis), FDA approved for afib Rivaroxaban (Xarelto), FDA approved in 2011 for afib/VTE

Question 36

Dabigatran etexilate (Pradaxa) for afib/VTE

Answer 36

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

Question 37

Apixaban (Eliquis), FDA approved for afib Rivaroxaban (Xarelto), FDA approved in 2011 for afib/VTE

Answer 37

Direct inhibitors of Factor Xa | Superior to warfarin in preventing strokes and emboli for treatment of atrial fibrillation

Question 38

Tissue plasminogen activator

Answer 38

Serine protease convert plasminogn to plasmin plasmin degrades fibrin (desolves clot)

Question 39

Uses of Fibrinolytic drugs

Answer 39

ER rx for: acute myocardial infarction Ischemic stroke Deep vein thrombosis and pulmonary embolism

Question 40

Adverse effects of Fibrinolytic drugs

Answer 40

Hemorrhage from lysis of "physiological clots" Induce a systemic lytic state due t increased plasmin formation

Question 41

Inhibits thromboxane A2 production by irreversibly inactivating cyclooxygenase 1. Anti-platelet Drugs

Answer 41

Aspirin

Question 42

Aspirin uses

Answer 42

after AMI and thrombotic stroke (with thrombolytics) to prevent AMI and stroke in high-risk patients Anti-platelet Drugs

Question 43

ADP receptor blockers

Answer 43

Clopidogrel (PLAVIX) Ticagrelor

Question 44

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)

Answer 44

Clopidogrel- PLAVIX

Question 45

Binds REVERSIBLY to ADP receptor Acts more rapidly

Answer 45

Ticagrelor

Question 46

block binding of fibrinogen to the adhesion protein GPIIb/IIIa. Anti-platelet Drugs

Answer 46

Glycoprotein IIb/IIIa inhibitors