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Flashcards in Coag Drugs Deck (29):
1

What does tPA do? What endogenous substance can inhibit it?

fibrinolysis via plasminogen --> plasmin
(plasmin will lyse the clot)

plasminogen activator inhibitor 1

2

What is the last step in the coag pathway?

fibrinogen --> fibrin

3

Clotting factors synth in liver?

II, V, VII, IX, X

4

What clotting factors need vitamin K?

II, VII, IX, X

5

Clotting factors targeted (most commonly) for pharm intervention?

II, X

6

Heparin MOA:

bind antithrombin III, increasing its affinity for X
(*makes thrombin inactivation more favorable)

7

Pathophys of HIT?

PF4 binds heparin (pt on hep for 5-10d)
Antibodies against hep/PF4 form, which:
--activate platelets to form arterial clots
--causes more PF4 release from platelets (destroys endothelial cells)

8

MOA of warfarin (coumarin)

vitamin K antagonist; by binding to vit K sites, it blocks:

1. carboxylation of glutamic acid on II, VII, IX, X, C, S (*liver and some in circulation)

2. binding of vit K to epoxide reductase (this enzyme reduces the oxidized-VitK)

9

Why is warfarin onset delayed?

1. long warfarin half life
2. pre-existing factors are slowly cleared from blood

*note: C/S are cleared more quickly, so you can actually be more coag in the first couple days; this is why you heparinize patients, then give them oral warfarin

10

What is warfarin rx to treat?

DVT, PE, a-fib, rheumatic heart disease, mechanical/prosthetic heart valves

11

What are some of the downsides to warfarin and other vitK antagonists?

slow onset
narrow therapeutic window
variability among patients
food/drug interactions (CYP2C9)
unpredictable
requires monitoring and dose-adjustment

*have to keep pts between INR of 2-3

12

How does low-mol-wt heparin differ from unfractioned heparin?

low-mol-wt:
cannot stabilize thrombin (its smaller)
is more effective in binding Xa

*are there more??

13

What are some uses/benefits of LMW heparin?

DVT prophylaxis (hip/abd srx)
no clotting test needed
longer duration/halflife
less binding to cellular proteins
more predictable

14

Thrombin binding site exosite 1 functions in:

binding fibrinogen
interacts w thrombomodulin, protein C platelet activation

15

Thrombin binding site exosite 2 functions in:

binding antithrombin
heparin binding site

16

Direct thrombin inhibitors don't require:

antithrombin III

FYI: most of these drugs are cleared by the kidneys. just an unrelated side note.

17

What drugs can be used in patients with HIT?

Direct thrombin inhibitors

18

What are some uses/benefits of Direct thrombin inhibitors?

no coag monitoring
higher therapeutic index
no CYP effects
predictable
fixed dosing
rapid onset of action

downside:
no antidote
monitor hepatic enzymes

19

How do dabigatran and hirudin differ?

dab binds reversibly to the thrombin active site

20

Fibrin bound thrombin is resistant to:
(Why is this notable?)

inactivation by heparin-ATIII complex
(heparin binding site is no longer accessible)

even when bound, thrombin is enzymatically active and can be used to amplify the coag cascade

21

Direct thrombin inhibitors prevent the activation of what clotting factors by thrombin?

V, VIII. XI, XIII

(also, platelets)

22

What anti-coags can inhibit free and bound heparin?

direct thrombin inhibitors
direct factor Xa inhibitors

23

What are some benefits of direct factor Xa inhibitors?

no interaction with food/drugs
reversible
predictable
no monitoring

24

Why are direct factor Xa inhibitors so effective?

they can act on the intrinsic AND extrinsic pathways

act on a step in amplification (1X can activate 1,000 thrombin molecules)

25

Blocking what receptor prevents fibrinogen cross-linking by activated platelets?

GpIIb/IIIa

26

What is the ADP receptor on platelets?

P2Y1

27

(Heparin/Warfarin) is used for acute therapy, whereas (Heparin/Warfarin) is used for chronic therapy.

1. heparin
2. warfarin

28

What drugs require antithrombin III for function?

unfractioned heparin
LMW heparin

29

Note: I skipped all the stuff that looks more like path, only covered the drugs

Week from hell.