BL- Antithrombotic drugs Flashcards Preview

BL/DD USMLE and Basics > BL- Antithrombotic drugs > Flashcards

Flashcards in BL- Antithrombotic drugs Deck (46):
1

interfere with the coagulation cascade and prevent thrombin formation.

Heparin and oral anticoagula

fibrinolytin--> thrombin--> fibrin

2

They lyse clots by increasing formation of plasmin

Fibrinolytic agents

fibrin--> plasmin-->degrade product

3

inhibit formation of platelet products or
block platelet adhesion preventing platelet aggregation and clot formation

. Anti-platelet agents.

4

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

Unfractionated Heparin

5

Depolymerized heparin- (~4500 daltons).
Better pharmkintetics

Low Molecular Weight Heparin (LMWH).

6

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

Fondaparinux. (type of heprin)

binds antithromin 3

7

Examples of pathologic thrombi formation

Formation of thrombus in atrial fibrillation

Formation of deep vein thrombus (DVT)

Formation of thrombus on atherosclerotic plaque

8

Fibrin

required for a stable clot

9

Three types of heprin

Unfractionated Heparin
Low Molecular Weight Heparin (LMWH)
Fondaparinux

10

Current Heprin Concerns

shortage- sourced by China
contamintaion- chondroitin sulfate

11

What does Heprin bind?

Antithrombin 3

12

How does heprin work

helps antithromin 3 inactivate coag factors

13

______dependent differences in action of heparins

Size

14

Unfractionted heprin binds

AT-3
2a
10a

15

Low molecular weight heprin (LMWH ) binds

AT-3
10a

16

Unfractionted heprin route/pharmkinetics

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

17

LMWH and fondaparinux route/pharmkinetics

Administered sub-cutaneously

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

Less monitoring (outpatient)

18

Uses of Heparins

Coronary angioplasty
stent placement
Surgery requiring cardiopulmonary bypass
Kidney dialysis

19

Uses of Heparins
*Used with warfarin

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

20

Uses of Heparins
✪Used with fibrinolytics

myocardial infarction✪

21

Toxicity of Heparins

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

22

a. Discontinue drug

b. Effects are reversed with protamine sulfate.

Toxicity of Heparins
Bleeding

23

Oral Anticoagulants

Warfarin

24

Pharmacokinetics of Warfarin

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

25

Warfarin Used to prevent

Venous thromboembolism (used with heparin)

Embolism in patients with prosthetic valves or atrial fibrillation

Stroke, recurrent infarctions

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


Heparin-induced thrombocytopenia

27

Warfarin: Adverse effects and problems

Hemorrhage- administer vit. K/plasma

Crosses placenta - teratogenic

Drug interactions/food

Delayed onset of action

Requires monitoring

28

Dicumarol

precursor of warfrin

29

Warfrin is a _____ antagonist

Vit.K

30

a. Due to the contaminant oversulfated chondroitin sulfate

b. Activation of the contact system (bradykinin, complement)

Allergic Reaction to heprin

31

New oral anticoagulants

Direct thrombin or Factor Xa inhibitors

32

Direct thrombin or Factor Xa inhibitors Advantages

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

33

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

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

Dabigatran etexilate (Pradaxa) for afib/VTE

35

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

36

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

37

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

38

Tissue plasminogen activator

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

39

Uses of Fibrinolytic drugs

ER rx for:

acute myocardial infarction

Ischemic stroke

Deep vein thrombosis and pulmonary embolism

40

Adverse effects of Fibrinolytic drugs

Hemorrhage from lysis of "physiological clots"

Induce a systemic lytic state due t increased plasmin formation

41

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

Aspirin

42

Aspirin uses

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

Anti-platelet Drugs

43

ADP receptor blockers

Clopidogrel (PLAVIX)

Ticagrelor

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)

Clopidogrel- PLAVIX

45

Binds REVERSIBLY to ADP receptor

Acts more rapidly

Ticagrelor

46

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

Glycoprotein IIb/IIIa inhibitors