Mda Dr. Smith Anticoagulants, Antiplatelets And Thrombolytic

Front 1

What does Heparin do?

Back 1

It accelerates the binding of the antithrombin to thombin and Xa to prevent conversion on fibrinogen to fibrin.

Front 2

What does Low Molecular Weight Heparin do?

Back 2

Selective for Xa

Front 3

Do LMW Heparins require aPTT monitoring?

Back 3

No becasue we are working up stream of factor IIa and factor IIa is the RLS

Front 4

What are the different types of LMW Heparin?

Back 4

- enorxaparin
- dalteparin
- tinzaparin

Front 5

What is LMW heparin used to treat?

Back 5

It treats venous thromboembolism and acute coronary syndromes. It is also used in deep venous thrombosis postop or preop by sc administration

Front 6

Unlike Heparin, LMW heparin is less likely to produce what?

Back 6

heparin induced thrombocytopenia

Front 7

Can LMW heparin accumulate? If so in which patient population

Back 7

Yes it accumulates in patients with renal failures. The way to prevent accumlation is to adjust the dose.

Front 8

Does Protamine work against LMW heparin?

Back 8

NO NO NO because LMW heparin has different stereochemistry

Front 9

Is Heparin's half life longer or shorter than LMW heparin's half life?

Back 9

Heparin has a shorter half life than LMW Hep.

Front 10

What is Ximelagatran?

Back 10

It is an orally active direct thrombin inhibitor but it is not used to US because it causes liver toxicity and bleeding. But if we can find something like this drug then we can replace WARFARIN!

Front 11

What kind of drug is fondaparinux?

Back 11

It works by inhibiting factor Xa. It is highly selective for factor Xa. It is used for prophylaxis of deep venous thrombosis

Front 12

How do you administer fondaparinux?

Back 12

SC or IV

Front 13

The protein factors (zymogens) are synthesized and controlled by what?

Back 13

The factors are all synthesized in the liver and they are controlled by Vit K (factors II, VII, IX, X). These factors react with Ca2+

Front 14

What does Warfarin do?

Back 14

It antagonizes the Vit K dependent carboxylation factors such as II, VII, IX and X. It also antagonizes anticoagulant proteins C and S.

Front 15

How is warfarin monitored?

Back 15

prothombin time adjusted to INR

Front 16

What are protein C and S?

Back 16

They are natural proteins that are carboxylated and they put a break on coagulation.

Front 17

Mechanism of Warfarin?

Back 17

It blocks the de novo synthesis of new clotting factors. It blocks that step going from KO to KH2.

Front 18

How long will it take for us to see effects of warfarin? And why does it take that amt of time?

Back 18

3-5 days. This is because the half lives of the clotting factors will last days. And warfarin only works on the de novo synthesis of new clotting factores and so this means that we will have to wait for the clotting factors that are already in the circulation to die out. Therefore we will not see changes in the INR for 3-5 days

Front 19

What other drug should be prescribe when patients initially start using warfarin?

Back 19

LMW heparin to ensure that patients are still able to have anticoagulant effects.

Front 20

Explain the early prothrombic effect that may occur when starting to use Warfarin?

Back 20

Warfarin antagonizes Protein C, a natural anticoagulant, first before it affects Vit K dep factors. therefore, patients run the risk of forming clots when they first switch over to warfarin when the anticoagualtion isnt' working yet.

Front 21

Why does warfarin have alot of DDI?

Back 21

Warfarin binds tightly to plasma proteins and so when there is another drug, there is competition for the binding site. Warfarin binds so tightly to proteins that only 1% is unbound that will cause effect. Therefore when there is competition, there will be more unbound drugs more say 2% unbound and that is significant change and will cause alot of effects.

Front 22

What will happen if you are on warfarin but you decide to eat lots of veggies? What will happen to your INR?

Back 22

Increase in Vit K from the vegetables. Although warfarin inhibits the reduction process of vitamin K, Vit K can still find its way around to get to cells that goes directly to KH2. therefore eating lots of veggies will increase Vit K, which will decrease the INR (shorter time to clot now).

Front 23

When are thrombolytic drugs used?

Back 23

they are used to resolve preexisting clots from MI, Stroke, etc.

Front 24

What do the thrombolytic drugs do?

Back 24

They increase the degradation of fibrin by plasmin.

Front 25

What is the precursor of plasmin?

Back 25

Plasminogen

Front 26

What is urokinase?

Back 26

It is a recombinant that converts plasminogen to plasmin.

Front 27

How is the plasmin produced by urokinase different than the regular plasmin that is produced by tissue plasminogen activator?

Back 27

The plasmin produced by urokinase is not fibrin specific so it will cut up anything that looks like fibrin.

Front 28

Why do you get a higher incidence of bleeding with urokinase?

Back 28

B/c the plasmin is not fibrin specific. It will degrad fibrinogen which is something we need to help clot but it will cut that up and that will lead to bleeding.

Front 29

Tissue Plasminogen Activator (t-PA)

Back 29

Converts plasminogen to plasmin at recommended doses. If clinician uses a dose higher than it may lead to lose of fibrin

Front 30

Name the agents that are in t-PA class

Back 30

alteplase
reteplase
tenecteplase

Front 31

Name a drug that is used when you have sepsis and you need to restore Protein C

Back 31

Drotrecogin alfa - used during severe sepsis. B/c the bacteria will feel on protein c and that will lead to coaguopathy. But this drug is rarely used only when you have severe case of sepsis.

Front 32

What do antiplatelet drugs do?

Back 32

Inhibit platelet aggregation to reduce thrombi in the arterial vasculature.

Front 33

Explain the pathway of platelet aggregation

Back 33

Collagen exposed due to break. Collagen binds to platelets and it activates the glycoprotein receptor.
Also the von willinbin factor which
also exists in circulation can bind
and activate another glycoprotein
receptor. these two systems
stimulate the release of ATP, expression of TxA2 from
Cox. ANd it also cause
sprouting of the
expression of the surface
glycoprotein that binds to
fibrinogen. So in this situation,
we have platelet adhesion and gives raise to bridging. The bridging of the two platelets come together. this bridging is called
platelet aggregation. this is
distinct from platelet adhesion.
We dont have a way to block
adhesion but we can antagonize
the proliferation of these receptors

Front 34

What does Aspirin do?

Back 34

Inhibits Cox mediated synthesis of thromboxane A2 and this is irreversible by acylation.

Front 35

Why is the antiplatelet effect of aspirin long lasting?

Back 35

It irreversibly inhibits Cox and the platelets are anucleated

Front 36

Give examples of ADP antagonist

Back 36

Clopidogrel
Ticlopidine
both agents binds irreversibly to ADP receptors on platelets. And this inhibits aggregation.

Front 37

GIve an example of PDE III inhibitor

Back 37

Cilostazol

Front 38

MDA of cilostazol

Back 38

Inhibition of phosphodiesterase which results in increase cAMP, and that causes vasodilation and also it inhibits platelet aggregation (bridge forming)

Front 39

Drugs that are IIb/IIIa antagonists

Back 39

Abciximab
Eptifibatide
Tirofiban

Front 40

What does abciximad do?

Back 40

an antibody against IIb/IIIa complex and it prevents the fibrinogen bridge from occuring. SEE SLIDE 36

Hint 40

What does abciximad do?

Front 41

What do eptifibitide and tirofiban do?

Back 41

These two drugs bind to the receptors reversibly. They occlude the area temporary and they dont induce alot of bleeding. It inhibits aggregation.

Front 42

What does Dipyridamole do?

Back 42

Inhibits phosphodiesterase and reuptake of adenosine which results in the decrease activity and platelet aggregation.

Front 43

What is dipyridamole used for?

Back 43

postop cardiac valve replacement or reduce risk of stroke in patients with TIA.

Front 44

Dipyridamole is used in conjunction with what drugs?

Back 44

Warfarin (valve replacement)
Aspirin (reduce risk of stroke)

Front 45

What is thrombocytopenia?

Back 45

reduction in platelet count

Front 46

What is thrombocythemia

Back 46

increase in platelet count.

Front 47

What does Anagrelide do?

Back 47

selectively reduces platelet counts by reduction in megakaryocyte maturation.

Front 48

What is anagrelide used for

Back 48

used for thrombocythemia