Pharmacology - Anticoagulants Flashcards Preview

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Flashcards in Pharmacology - Anticoagulants Deck (43):
1

Anticoagulants – venous thrombosis include:

Heparins
Vitamin K antagonist
Direct thrombin inhibitors
Direct Xa inhibitors

2

Cox inhibitor
P2Y12 (ADP receptor) inhibitors
GPIIbIIIa (fibrinogen receptor) inhibitors
Phosphodiesterase inhibitors

These are what kinds of drugs?

Antiplatelet Drugs - arterial thrombosis

3

T/F: Anticoagulants do not lyse already formed clots, but prevent their further propagation

True
Use TPA for acute thrombosis

use Anticagulants to prevent thromboses in low shear environments is heart in a-fib, valvular disease and valve replacement

4

These are _______ drugs:
Aspirin
Dipyramole
Clopidogrel
Presugrel
Ticagrelor
Abciximab
Eptifibatide
Tirofiban

Antiplatelet drugs - used in arterial thrombosis

5

These are _____ drugs:
Alteplase
Tenecteplase
Reteplase

Fibrinolytic drugs
lyse clots acutely

6

Class Warfarin:

Vitamin K antagonist

7

MOA Warfarin:

Blocks Vitamin-K-dependent gamma-carboxylation of factors II, VII, IX, X, protein C and S
***7-9-10-2*** remember this
**does not affect already synthesized factors

8

Thrombin is aka:

activated factor 2 (clotting cascade)

9

Unfractionated and low molecular weight heparin act on what parts of the clotting cascade:

10a, thrombin

10

Apixaban and Rivaroxaban act on what part of the clotting cascade?

They are direct 10a inhibitors
Reversibly bind active site of 10a

11

Therapeutic Uses:
Apixaban
Rivaroxaban

DVT/PE prophylaxis

12

Side effects:
Apixaban
Rivaroxaban

Bleeding (duh, they're anticoagulants)

13

Skin necrosis is a side effect of what anticoagulant?

Warfarin
Other side effects:
bleeding;
thrombosis is a warfarin side effect bc of protein C lowering

14

Therapeutic use of warfarin for long-term anticoagulation is particularly useful bc it lacks what toxicity?

Warfarin has no major organ toxicities, so OK for lifelong therapy

15

Mode of administration of unfractionated heparin is IV for what 2 reasons?

Big molecule
short half life

16

T/F: Dosing of unfractionated heparin can be unpredictable bc it binds to everything basically, ie cell surface glycoproteins, vitronectin, platelet factor four etc.

True

The binding to factor 4 makes a highly immunogenic compound that is responsible for HIT

17

MOA Unfractionated Heparin

Binds antithrombin

Heparin-AT complex inactives IIa, Xa, IXa, XIa, XIIa

18

Uses: unfractionated heparain

prevention/tx of venous thromboembolism

19

MOA:
Dalteparin
Enoxaparin

LMWH
inhibits thrombin less effectively than factor Xa

longer half life, less monitoring necessary

20

What anticoagulant is preferred for use in pregnancy?

Enoxaparin
indirect thrombin inhibitor
LMWH
monitor with heparin assay instead of PTT (unfractionated heparin)

21

What test do you use to monitor warfarin therapy?

PT (expressed as INR)

22

Too low warfarin can cause clots bc:

warfarin also inhibits the carboxylation of anticoagulants protein S and C, which may induce thromboembolism (for example at the onset of therapy)

To avoid it, warfarin is always started while on heparin.

23

Bivalirudin
Argatroban
Dabigatran

These drugs are:

Direct thrombin inhibitors

24

MOA: Direct thrombin inhibitors
Bivalirudin
Argatroban
Dabigatran

Inactivate thrombin both bound and unbound to fibrinogen

Bind to the catalytic site of thrombin
Immediate onset
No antidote (under development)

25

Therapeutic Uses:
Bivalirudin
Argatroban

percutaneous coronary intervention (PCI)

monitor with PTT

26

Therapeutic Use: Dabigatrain

DVT/PE
Afib

27

What anticoagulantis preferred for use in cancer patients?

Unfractionated heparin

28

Therapeutic uses:
Dalteparin
Enoxaparin

Use in pregnancy;
unstable angina

29

Dosing of warfarin is difficult because:

1. Competes with Vitamin K
– Vitamin K is influenced by diet, diarrhea, laxatives, antibiotics, fat absorption
2. >99% is bound to albumin – Interference by other drugs
3. Hepatic metabolism
– Enhanced by barbiturates, rifampin
– Inhibited by metronidazole, amiodarone, disulfiram.......
4. Fluctuation of the cascade

30

How would you reverse the effects of warfarin?

1. Stop warfarin
2. Give vitamin K
3. Give Prothrombin factor concentrate (Kcentra: Factors II, VII, IX, X, Protein C+S)
4. Give fresh frozen plasma (FFP) (until recently, this was common practice)

31

Name the direct Xa inhibitors.

Rivaroxaban
Apixeban

reversibly bind active site of Xa

for DVT/PE prophylaxis

32

Even though Apixaban did well in clinical trials, still the only anticoagulant preferred for valvular disease is:

warfarin

33

MOA: Fibrinolytics
Alteplase
Tenecteplase
Reteplase

activate plasminogen --> plasmins
lyse clots

for STEMI

34

Therapeutic Use: Alteplase

STEMI, acute stroke, PE

35

How is Tenecteplase differenct from the other fibrinolytics (Alteplase, Reteplase)?

Clot-specific, long half-life

36

Therapeutic Uses: Antiplatelet Drugs
Aspirin
Dipyramole
Cilostazol
Clopidogrel

 Myocardial infarction (MI)
 Stroke/Transient Ischemic attack (TIA)
 Peripheral arterial disease (PAD)
 Percutaneous coronary intervention (PCI)

37

MOA Abciximad

MAB against GP2b/3a

38

MOA:
Dipyramole
Cilostazol

Phophodiesterase (PDE) inhibitor --> increase in platelet cAMP

 Dipyridamole
--Used alone or with aspirin
--Secondary stroke prevention
 Cilostazol
– Peripheral arterial disease
– Also reduces smooth muscle proliferation and intimal hyperplasia

39

MOA Clopidogrel

P2Y12 (ADP Receptor) Blocker

prevent and treat ACS, stroke, PVD, angina, stent

40

T/F: Dabigatran is a prodrug.

True
Direct thrombin inhibitor
metabolized in the liver to active form

41

Take a moment to read about the αIIbβ3- Integrin (GPIIb/IIIa, Fibrinogen Receptor) Inhibitors (antiplatelet family).

They are Parenteral drugs

 Abciximab
– monoclonal antibody: Fab’2 fragment of chimeric mouse/human – immune response prevents repeated use
– effective for 24-48 hours

 Eptifibatide
– rattlesnake venom peptide fibrinogen analog
– rapid onset, short half-life and reversible action

 Tirofiban
– tyrosine derivative fibrinogen analog

42

The effects of cytokines, such as IL-1, are mediated by receptors that cause:

tyrosine phosphorylation
other autacoids – histamine, serotonin, the kinins, and eicosanoids – bind to G- protein-coupled membrane receptors that are themselves not tyrosine kinases

43

The NSAIDs inhibit the cyclooxygenases, which convert arachidonic acid into prostacyclins, prostaglandins, and thromboxanes. They do not inhibit:

lipoxygenase, which converts arachidonic acid into the leukotrienes.