Anticoagulation/AntiThrombotic Therapy

Question 1

Effects of thrombin

1. Forms and ____ the ___ clot.
2. Stimulates TAFI: what is this?

Answer 1

Effects of thrombin

1. stabilizes; fibrin
2. Thrombin Activated Fibrinolysis Inhibitor

Question 2

Fibrolytic Pathway

1. Activators converting plasminogen to plasmin?
2. Inhibitors of plasminogen to plasmin conversion?

Answer 2

Fibrinolytic pathway

1. Urokinase type plasminogen activator and tissue type
2. Plasmin activator inhibitiors (PAI-I or PAI-II)

Question 3

Fibrinolytic pathway

Inhibitors of plasmin itself?

Answer 3

Fibrinolytic pathway

a. Alpha1-antitrypsin
b. alpha2-antiplasmin
c. Thrombin-activatable fibrinolysis inhibitor

Question 4

Anti-Platelet therapy:

Drugs?

Answer 4

Anti-Platelet therapy:

a. Aspirin
b. Thienopyridines
c. G IIb/IIIa receptor antagonists
d. PAR-1 inhibitor

Question 5

Anti-Platelet therapy:

Aspirin:

1. Mechanism of action?
2. How can effects be reversed?
3. Clinical implications?

Answer 5

Anti-Platelet therapy:

Aspirin:

1. Irreversibly inhibits COX activity of PG synthesis
2. Can only be reversed by new platelet generation
3. Once daily dosing (and prolonged dissipation of anti-platelet effect)

Question 6

Anti-Platelet therapy:

Thienopyridines:

Drugs?

Answer 6

Anti-Platelet therapy:

a. Ticlopidine
b. Clopidogrel
c. Prasugrel
d. Ticagrelor

Question 7

Anti-Platelet therapy:

Thienopyridines (ticlopidine/clopidogrel/prasugrel/ticagrelor)

What do they inhibit? What is the result?

Answer 7

Anti-Platelet therapy:

Thienopyridines:

These are ADP receptor inhibitors and thus inhibit platelet aggregation

Question 8

Anti-Platelet therapy:

Clopidogrel:

Mechanism of action?

How is it inactivated? What is this a problem with?

Peak level? Half life is longer than?

Answer 8

Anti-Platelet therapy:

Clopidogrel:

Irreversibly inhibits ADP binding to platelet P2Y12 receptor

Can only generate new platelets; issue with surgery

Peaks within an hour of ingestion; longer T1/2 than aspirin

Question 9

Anti-Platelet therapy:

ADP receptor inhibitors:

1. Intake of what is restricted when taking Ticagrelor?
2. Who should not take Prasugrel?

Answer 9

Anti-Platelet therapy:

ADP receptor inhibitors:

1. Aspirin intake, must be less than 100mg
2. Patients over 76 or who weigh under 60kg shouldnt take prasugrel

Question 10

Anti-Platelet therapy:

What drug had bad marketing on reduction in CVA patients?

Answer 10

Anti-Platelet therapy:

Vorapaxor

Question 11

Anti-Platelet therapy:

Glycoprotein IIb/IIIa inhibitors:

1. What does it bind to?
2. What stage is it important for in platelet aggregation?
3. What are the 3 in use? Route of administration?

Answer 11

Anti-Platelet therapy:

Glycoprotein IIb/IIIa inhibitors:

1. vWF and fibrinogen
2. Final common pathway
3. Abciximab, Eptifibatide, Tirofiban; given IV only

Question 12

Anti-Platelet therapy:

Abciximab:

1. What is this? Function?
2. Size? Duration of action?
3. Binding?

Answer 12

Anti-Platelet therapy:

Abciximab:

1. Fab fragment of ab against IIb/IIIa
2. Large; Long duration of action
3. nonspecific

Question 13

Anti-Platelet therapy:

Eptifibatide and Tirofiban:

1. Highly ___ and ___ inhibitors of what receptor?
2. Half life? Speed of recovery of platelet function?
3. ___% inhibition of platelet aggregation

Answer 13

Anti-Platelet therapy:

Eptifibatide and Tirofiban:

1. Highly selective and reversible inhibitors of IIb/IIIa
2. short half life; fast recovery of platelet function
3. 80% inhibition of platelet aggregation

Question 14

Anticoagulant classes:

1. Inhibitors of clot initiation are blocking what pathway?
2. Inhibitors of clot propagation are blocking what factor?
3. Inhibitors of the fibrin formation are inhibiting?

Answer 14

Anticoagulant classes:

1. VIIa/TF pathway (clot initiation)
2. Factor Xa inhibitors (clot propagation)
3. Direct thrombin inhibitors (fibrin formation)

Question 15

Anti-Thrombosis:

Antithrombin agents (name 3)

Answer 15

Anti-Thrombosis:

Antithrombin agents:

a. Heparin
b. Low molecular weight heparin
c. Direct Thrombin inhibitors

Question 16

Anti-Thrombosis:

Unfractionated Heparin:

1. These are nonselective inhibitors of?
2. Binds to?
3. Elimination not dependent on?

Answer 16

Anti-Thrombosis:

Unfractionated heparin:

1. Factor Xa inhibitors (inhibit clot propagation)
2. Binds to endothelial cells and plasma proteins
3. Elimination is not dependent on renal function

Question 17

Anti-Thrombosis:

Unfractionated heparin:

1. What does it stimulate? (that it doesnt want)
2. What does it release? (that is good)
3. What is its cofactor?

Answer 17

Anti-Thrombosis:

Unfractionated heparin:

1. Simulates platelets and releases platelet factor 4
2. Tissue factor pathway inhibitor
3. Requires Anti-thrombin III as a cofactor

Question 18

Anti-Thrombosis:

Antihemostatic effects of Heparin:

1. What factors does it inactivate?
2. Role in platelet function?

Answer 18

Anti-Thrombosis:

Antihemostatic effects of heparin:

1. Inactivates factors IIa, IXa, Xa, and XIIa
2. Inhibits platelet function and contributes to the hemorrhagic effects of heparin

Question 19

Anti-Thrombosis:

Limitations of Unfractionated Heparin:

1. Unpredictable what?
2. Narrow ____ window
3. Reduced activity in the vicinity of ___ ____ ___
4. It can also ___ clotting.

Answer 19

Anti-Thrombosis:

Limitations of UFH:

1. Unpredictable anticoagulant response
2. Narrow therapeutic window
3. Reduced activity in the vicinity of platelet-rich thrombi
4. It can also ACTIVATE clotting

Question 20

Anti-Thrombosis:

Advantages of LMWH vs. UFH:

1. Administration?
2. More ___ anticoagulant response.
3. Half life?
4. Lower incidence of _____.

Answer 20

Anti-Thrombosis:

Advantages of LMWH vs. UFH

1. LMWH is easier to administer (subcutaneous not IV)
2. More predictable anticoagulant response
3. LMWH has a half life that is 2-4x longer
4. Lowers the incidence of thrombocytopenia

Question 21

Anti-Thrombosis:

UFH:

This must be monitored: monitoring the therapeutic range with?

Answer 21

Anti-Thrombosis:

UFH:

PTT - Partial thromboplastin time

Question 22

Vitamin K Antagonists:

Name 6 drugs.

Answer 22

Vitamin K Antagonists:

a. Warfarin
b. Dicoumarol
c. Phenprocoumon
d. Indandione
e. Acenocoumarol
f. Anisindione

Question 23

Vitamin K Antagonists:

Warfarin:

1. What factors and protiens are vitamin K dependent?
2. These coagulation factors are biologically inactive unless ____ and this is dependend on ___ vitamin K
3. What enzyme does warfarin inhibit?

Answer 23

Vitamin K Antagonists:

Warfarin:

1. Factors II, VII, IX, and X as well as protein C and S are K depenent
2. They are inactive unless decarboxylated which depends on reduction of vitamin K
3. Vitamin K Oxide Reductase

Question 24

Vitamin K Antagonists:

Warfarin:

1. Effect on already carboxylated molecules?
2. Anticoagulant effect depends on depletion of ___ ___ in circulation.

Answer 24

Vitamin K Antagonists:

Warfarin:

1. No effect on already carboxylated molecules
2. Depends on depletion of carboxylated proteins in circulation (this depends on half lives)

Question 25

Vitamin K Antagonists: Pharmacokinetics of Warfarin: 1. Inter-individual sensitivity to warfarin is EXTREMELY \_\_\_. 2. Intra-individual sensitivity is _____ affected by multiple factors: nutrition and ___ \_\_ intake, gut \_\_\_\_, and \_\_\_.

Answer 25

Vitamin K Antagonists: Pharmacokinetics of Warfarin: 1. Interindividual sensitivity is EXTREMELY _variable_ 2. Intraindividual sensitivity is _MARKEDLY_ affected by multiple factors: nutrition and _vitamin K_ intake, gut _flora_, and _medications_

Question 26

Vitamin K Antagonists: Problems with Warfarin: 1. ______ dose response. 2. ____ therapeutic range 3. Bleeding? 4. Monitoring? 5. Reversibility?

Answer 26

Vitamin K Antagonists: Problems with Warfarin: 1. _Unpredictable_ dose response 2. _Narrow_ therapeutic range 3. High bleeding rate 4. Difficult to monitor 5. Slow reversibility

Question 27

Stroke in Atrial Fibrillation In comparison to stroke without AF, how is stroke with AF?

Answer 27

Stroke in Atrial fibrillation Strokes are more severe and disabling in patients with AF

Question 28

Risk factors for stroke in Non-valvular AF: 1. Use \_\_\_\_\_ score. 2. What is worth 1 point? 3. What is worth 2 points?

Answer 28

Risk factors for stroke in Non-valvular AF: 1. CHADS2 score 2. CHF, hypertension, Age (75+), Diabetes 3. Stroke or TIA in the past

Question 29

Antithrombic therapy in AF based on CHADS score: What do you give for a patient with a score of: 1. 0? 2. 1? 3. 2+?

Answer 29

Antithrombic therapy in AF based on CHADS score: 1. Score of 0 = aspirin 2. Score of 1 = Aspirin or Warfarin 3. Score of 2+ = Warfarin

Question 30

Warfarin Dosing: monitored by?

Answer 30

Warfarin dosing is monitored by PT (prothrombin time) extrensic pathway

Question 31

Pentasaccharide: Mechanism of action: Produces an irriversible ____ change in \_\_\_\_, which binds to and inhibits factor \_\_\_\_. It thus inhibits clot \_\_\_\_\_\_.

Answer 31

Pentasaccharide: Produces an irreversible _conformational_ change in _antithrombin_ which binds to and inhibits factor _Xa_. It thus inhibits clot _propagation_

Question 32

Fondaparinux: 1. Indirect inhibition of Factor \_\_\_. This is via \_\_\_\_. 2. ____ selective. 3. ____ inhibit thrombin activity 4. ____ inhibit thrombin generation 5. FDA approved for?

Answer 32

Fondaparinux: 1. Indirect inhibition of Factor _Xa_. This is via _AT-III_ 2. _Highly_ selective 3. _DOESNT_ inhibit thrombin activity 4. _DOES_ inhibit thrombin generation 5. FDA approved for DVT prophylaxis in hip fracture, TKA/THA (Total hip/knee arthroplasty)

Question 33

Direct Thrombin Inhibitors: What ones are bivalent? What ones are Univalent?

Answer 33

Direct Thrombin Inhibitors: Bivalent - Hirudin and Bivalirudin Univalent - Argatroban, dabigatran, ximelagatran

Question 34

Potential advantages of direct inhibitors: 1. Affect only one factor: \_\_\_ 2. Independent of \_\_\_\_ 3. Inhibition of thrombin-mediated activation of? 4. Active against what types of thrombin?

Answer 34

Potential advantages of direct inhibitors 1. Thrombin 2. Independent of AT-III 3. Inhibition of activation of clotting factors (V, VIII, and XIII) and platelets 4. \*\*\*\*\*Active agains free and clot-bound thrombin

Question 35

Which direct thrombin inhibitors are given IV? Which are given orally?

Answer 35

Bivalirudin and Argatroban are IV Ximelagatran and Dabigatran are oral

Question 36

Bilavirudin: 1. Partially ____ binding 2. No inhibition of thrombin \_\_\_\_ 3. FDA approved for? 4. Direct ____ thrombin binding.

Answer 36

Bilaviruden: 1. reversible 2. NO inhibition of thrombin generation 3. FDA approved for anticoagulation during PCI (Percutaneous coronary intervention) 4. Direct _bivalent_ binding

Question 37

Argatroban 1. Type of binding? 2. Excretion? 3. FDA approval for treatment of?

Answer 37

Argatroban 1. Reversible competitive binding 2. Hepatic excretion 3. FDA approval to treat HIT and for PCI in patients with a history of HIT (Heparin Induced Thrombocytopenia)

Question 38

New oral Anticoagulants: What two new drugs are Direct Xa inhibitors used for DVT and nonvalvular Afib? What is Pradaxa? For?

Answer 38

New oral anticoagulants: Xarelto and Eliquis (Direct Xa inhibitors) Pradaxa - direct thrombin inhibitor for nonvalvular Afib and DVT

Question 39

Fibrinolytic Therapy: 1. TPA is released from endothelial cells but rapidly cleared by? 2. What is protected from inhibition?

Answer 39

Fibrinolytic Therapy: 1. Cleared by PAI-1 and PAI-II 2. Fibrin-bound plasmin is protected from inhibition

Question 40

Fibrinolytic Therapy: Agents? (4)

Answer 40

Fibrinolytic Therapy: a. Streptokinase b. Reteplase c. Tenecteplase (TNK) d. Wild-type TPA

Question 41

Fibrinolytic Therapy: Wild-type t-PA: 1. Activates what kind of plasminogen? 2. Route of administration? 3. Half life?

Answer 41

Fibrinolytic Therapy: Wild-type t-PA: 1. Activates bound plasminogen several hundred-fold more rapidly than circulating plasminogen 2. IV (continuous infusion) 3. Very short

Question 42

Fibrinolytic Therapy: All fibrinolytic agents have the ptoential to cause?

Answer 42

Fibrinolytic Therapy: All can cause very serious bleeding including a very small incidence of intracranial hemorrhage

Question 43

Clinical role for lytics?

Answer 43

Acute MI, stroke, pulmonary emboli, declot IV catheters/dialysis accesses, and DVT