Pharmacology - Anticoagulants

Question 1

Anticoagulants – venous thrombosis include:

Answer 1

Heparins
Vitamin K antagonist
Direct thrombin inhibitors
Direct Xa inhibitors

Question 2

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

These are what kinds of drugs?

Answer 2

Antiplatelet Drugs - arterial thrombosis

Question 3

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

Answer 3

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

Question 4

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

Answer 4

Antiplatelet drugs - used in arterial thrombosis

Question 5

These are _____ drugs:
Alteplase
Tenecteplase
Reteplase

Answer 5

Fibrinolytic drugs

lyse clots acutely

Question 6

Class Warfarin:

Answer 6

Vitamin K antagonist

Question 7

MOA Warfarin:

Answer 7

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

Question 8

Thrombin is aka:

Answer 8

activated factor 2 (clotting cascade)

Question 9

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

Answer 9

10a, thrombin

Question 10

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

Answer 10

They are direct 10a inhibitors

Reversibly bind active site of 10a

Question 11

Therapeutic Uses:
Apixaban
Rivaroxaban

Answer 11

DVT/PE prophylaxis

Question 12

Side effects:
Apixaban
Rivaroxaban

Answer 12

Bleeding (duh, they’re anticoagulants)

Question 13

Skin necrosis is a side effect of what anticoagulant?

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

Big molecule

short half life

Question 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.

Answer 16

True

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

Question 17

MOA Unfractionated Heparin

Answer 17

Binds antithrombin

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

Question 18

Uses: unfractionated heparain

Answer 18

prevention/tx of venous thromboembolism

Question 19

MOA:
Dalteparin
Enoxaparin

Answer 19

LMWH
inhibits thrombin less effectively than factor Xa

longer half life, less monitoring necessary

Question 20

What anticoagulant is preferred for use in pregnancy?

Answer 20

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

Question 21

What test do you use to monitor warfarin therapy?

Answer 21

PT (expressed as INR)

Question 22

Too low warfarin can cause clots bc:

Answer 22

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.

Question 23

Bivalirudin
Argatroban
Dabigatran

These drugs are:

Answer 23

Direct thrombin inhibitors

Question 24

MOA: Direct thrombin inhibitors
Bivalirudin
Argatroban
Dabigatran

Answer 24

Inactivate thrombin both bound and unbound to fibrinogen

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

Question 25

Therapeutic Uses:
Bivalirudin
Argatroban

Answer 25

percutaneous coronary intervention (PCI)

monitor with PTT

Question 26

Therapeutic Use: Dabigatrain

Answer 26

DVT/PE

Afib

Question 27

What anticoagulantis preferred for use in cancer patients?

Answer 27

Unfractionated heparin

Question 28

Therapeutic uses:
Dalteparin
Enoxaparin

Answer 28

Use in pregnancy;

unstable angina

Question 29

Dosing of warfarin is difficult because:

Answer 29

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

Question 30

How would you reverse the effects of warfarin?

Answer 30

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)

Question 31

Name the direct Xa inhibitors.

Answer 31

Rivaroxaban
Apixeban

reversibly bind active site of Xa

for DVT/PE prophylaxis

Question 32

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

Answer 32

warfarin

Question 33

MOA: Fibrinolytics
Alteplase
Tenecteplase
Reteplase

Answer 33

activate plasminogen –> plasmins
lyse clots

for STEMI

Question 34

Therapeutic Use: Alteplase

Answer 34

STEMI, acute stroke, PE

Question 35

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

Answer 35

Clot-specific, long half-life

Question 36

Therapeutic Uses: Antiplatelet Drugs
Aspirin
Dipyramole
Cilostazol
Clopidogrel

Answer 36

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

Question 37

MOA Abciximad

Answer 37

MAB against GP2b/3a

Question 38

MOA:
Dipyramole
Cilostazol

Answer 38

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

Question 39

MOA Clopidogrel

Answer 39

P2Y12 (ADP Receptor) Blocker

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

Question 40

T/F: Dabigatran is a prodrug.

Answer 40

True
Direct thrombin inhibitor
metabolized in the liver to active form

Question 41

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

Answer 41

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

Question 42

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

Answer 42

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

Question 43

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

Answer 43

lipoxygenase, which converts arachidonic acid into the leukotrienes.