anticoagulation: pharm

Question 1

Three major natural anticoagulant pathways

Answer 1

1. Tissue factor pathway inhibitor (TFPI)
2. Protein C / Protein S pathway
3. Anti-thrombin III ** (AT-III)

Question 2

antithrombin AT inhibits coagulation:

Answer 2

1. thrombin IIa
2. FIXa
3. FXa
4. FXIa

Question 3

what accelerates AT inhibitor function by more than 1000x

Answer 3

heparin sulphate

Question 4

Heparin (3)

Answer 4

1. unfractionated heparin
2. low molecular weight heparins
3. synthetic pentasacchardie

Question 5

vitamin K antagonist

Answer 5

warfarin

Question 6

direct thrombin inhibitors do not need _____ to work

Answer 6

AT-III

Question 7

unfractionated heparin

1. bioavailability
2. administration
3. half-life
4. induces conformational change in _____ and augments it for neutralization of (4)
5. impairs ____ function
6. major adverse rxn

Answer 7

1. low bioavailability
2. poorly absorbed through GI thus it needs to be with SQ or IV
3. 1-2 hr. half life
4. induces conformational change in AT-III and augments it for neutralization of thrombin, Xa, IXa, XIa
5. impairs platelet function
6. HIT- heparin induced thrombocytopenia

Question 8

HIT

1. immune mediated?
2. occurs
3. happens more in
4. males vs females
5. thrombocytopenia
6. b/c ab complex activated endothelial cells it leads to
7. treatment

Answer 8

1. yep- IgG against heparin PF4 complex
2. occurs 4-10 days after starting heparin
3. UF> LMWH
4. females>males
5. low platelet count
6. thrombosis
7. stop all heparin and give a direct thrombin inhibitor instead until platelet count is normal and then we can start warfarin

Question 9

heparin neutralizing protein in alpha granules

Answer 9

platelet factor 4

Question 10

LMWH

1. common example
2. synthetic analogue
3. difference to UFH
4. fondaparinux? significance?
5. PTT prolongation?
6. monitoring?
7. platelet effect

Answer 10

1. enoxaprin-lovenox
2. pentasaccharide
3. b/c chains are smaller than UFH, LMWH inhibits factor Xa» IIa-thrombin
4. fondaparinux is a pure anti-Xa inhibitor which mediates effects through AT-III but there is no affinity for PF4 thus no HIT
5. PTT is minimally prolonged b/c thrombin is not max. inhibited
6. monitor- anti-Xa assay
7. less anti-platelet effect than UFH

Question 11

Anti- Xa: anti-IIa

UFH vs LMWH

Answer 11

UFH- 1:1

LMWH: 2:1 or 4:1

Question 12

monitoring

UFH vs LMWH

Answer 12

UFH: APTT
LMWH: anti-Xa assay

Question 13

frequency of HIT

UFH vs LMWH

Answer 13

UFH: high
LMWH: low

Question 14

fondaparinux has an antidote

Answer 14

nope

Question 15

reversal of heparin (2)

Answer 15

1. discontinue drug

2. protamine sulphate UFH»LMWH

Question 16

oral agent approved for stroke prevention in non-valvular atrial fibrillation; DVT, PE

Answer 16

dabigatran (direct thrombin inhibitor)

Question 17

direct thrombin inhibitor

1. hepatic clearance
2. renal clearance
3. how does it work?
4. chances of HIT
5. true or false: anticoag. response if predictable since they do not bind to endothelium or plasma proteins
6. drug interactions
7. antidote
8. monitoring

Answer 17

1. argatroban
2. bivalirudin- off label for HIT
3. inactivates thrombin bound to fibrin
4. not neutralized by PF4 released from platelets thus no HIT or thrombocytopenia
5. true
6. no know drug interactions
7. no antidote
8. no monitoring

Question 18

DTIs inactivate thrombin but unlike heparin it does so in an

Answer 18

antithrombin -independent fashion

Question 19

Warfarin

1. administration
2. half life
3. circulation
4. activity
5. inhibits
6. VKORCI is a key enzyme in
7. gamma carboxylation adds ____ which serve to
8. variability

Answer 19

1. oral- rapid absorption from gut
2. 36-42 hr half life
3. circulates free and bound to plasma proteins
4. only free warfarin is active
5. inhibits vit.k epoxide reductase subunit 1
6. VKORCI is a key enzyme in recycling of Vit. K
7. gamma carboxylation adds Gla residues to serve to anchor the clotting factors to phospholipid membranes via Ca2+ bridges
8. variable response within a single patient

Question 20

warfarin has Dose variability amongst patients due to variable metabolism

Answer 20

yep

Question 21

Warfarin lab monitoring

1. PT
2. PTT
3. Thrombin time

Answer 21

1. PT- acute prolongation due to fall in FVII
2. PTT- prolonged after a few days with decreased II, IX and X
3. thrombin time is not affected by warfarin

Question 22

thromboplastin reagent used in the PT assay is assigned an ISI (International Sensitivity Index) calibrated against a primary WHO standard thromboplastin

Answer 22

INR

Question 23

Bridging from Heparin or DTI to Warfarin

Answer 23

1. start warfarin while patient is still on heparin/DTI
2. continue heparin/DTI doses until at least 5 days to ensure full anticoag.
3. continue heparin/DTI until INR shows therapeutic levels

Question 24

complications of warfarin (3)

Answer 24

1. bleeding- supratherapeutic INR
2. skin necrosis in patients with protein C deficiency
3. teratogenic avoid in pregnancy

Question 25

direct oral agent 1. approved for use in stroke prevention in atrial fibrillation, DVT, PE 2. antidote for 1 3. monitoring 4. direct factor Xa inhibitor and antidote and monitonring

Answer 25

1. dabigatran 2. idarucizumab--humanized monoclonal antibody fragment which binds to dabigatran 3. no monitoring 4. rivaroxaban- andexxa alpha is the antidote and for monitoring you can use anti-Xa levels for monitoring

Question 26

A human protein derived from tissue culture using recombinant technology (a native protein so no immune response)

Answer 26

rtPA

Question 27

rtPA: 1. act 2. degrades 3. cleared from plasma

Answer 27

1. directly activates plasminogen 2. degrades fibrin clot 3. cleared from plasma in 4-8 minutes

Question 28

indications for trhombolytic therapy (2)

Answer 28

1. occluded central venous catheters (alteplase) | 2. life or limb threatening situations

Question 29

complications of thrombolytic therapy

Answer 29

1. intracranial hemorrhage

Question 30

are there contraidications to thrombolytic therapy

Answer 30

yep, major bleeds

Question 31

Thromboxane A2 inhibitor

Answer 31

aspirin- anti-platelet agent

Question 32

ADP-receptor antagonists

Answer 32

1. Clopidogrel (Plavix) 2. Prasugrel (Effient) * anti-platelet agent

Question 33

GPIIb/IIIa blockers

Answer 33

eptifibatide (Integrilin) * anti-platelet blocker

Question 34

PAR-1 receptor antagonists (thrombin)

Answer 34

Vorapaxar (Zontivity) * antiplatelet agent

Question 35

irreversibly acetylates cyclooxygenase preventing arachidonic acid conversion to prostaglandin and Thromboxane; impaired platelet aggregation ** indicated by secondary stroke, TIA

Answer 35

aspirin

Question 36

via P2Y12 receptor – inhibits platelet aggregation *indicated for ACS and PCI

Answer 36

ADP receptor antagonists

Question 37

These drugs reversibly inhibit platelet aggregation by binding of GPIIb/IIIa – the site fibrinogen binding between platelets

Answer 37

GPIIb-IIIa antagonists

Question 38

Thrombin receptor antagonists- thrombin activates platelets via PAR1 and 4

Answer 38

PAR-1 receptor antagonists (protease activated receptor)