Anticoagulant and Fibrinolytic Drugs Nov21 M2

Question 1

goal of these drugs

Answer 1

prevent thromboembolism

Question 2

3 steps of normal coagulation

Answer 2

1. retraction of vessel
2. platelets activation after factor exposure from endothelium
3. coagulation cascade

Question 3

white vs red thrombus

Answer 3

white in arterial blood

red in venous blood bc stasis, slow flow. more blood stuck in fibrin

Question 4

normal procoagulant vs anticoagulant factors present

Answer 4

pro: platelet adhesion, aggregation. fibrin clot formation
anti: fibrinolysis + natural inhibitors of coagulation

Question 5

anticoagulant drugs discussed

Answer 5

UF heparin, LMWH heparin, oral anticoagulants (warfarin, dabigatran, rivaroxaban, apixaban)

Question 6

fibrinolytic drugs discussed

Answer 6

alteplase (tissue plasminogen activator, a tPA), tenecteplase

Question 7

heparin descript

Answer 7

sulphated mucopolysacch occuring in mast cells

Question 8

heparin normal fct

Answer 8

cofactor of antithrombin III

Question 9

antithrombin III functions (3)

Answer 9

inhibits thrombin (IIa) and factor Xa
traps other coag factors, other proteases (suicide substrate)

Question 10

how express UF heparin dose

Answer 10

USP units

Question 11

heparin administration and why

Answer 11

IV or subcutaneous (latter = 1-2hr effect delay)

can’t GI bc mast cells destroy it

Question 12

how heparin degraded

Answer 12

macrophages. reticulo-endothelial system

Question 13

how monitor heparin dose

Answer 13

with activated partial thromboplastin time (aPTT)

Question 14

normal aPTT value

Answer 14

30-50 seconds

Question 15

uses of IV UF heparin

Answer 15

hospital. PE after DVT. DVT above knee joint. unstable angina. MI.

Question 16

uses of subcut UF heparin

Answer 16

bed-ridden or hosp patients not receiving IV heparin for prevention of DVT

Question 17

important UF heparin toxicities

Answer 17

• bleeding
• thrombocytopenia
• allergies

Question 18

why thrombocytopenia possible in UF heparin

Answer 18

transient + harmless in 25% of patients
5% get heparin-induced-anti-platelet antibodies (HIT) can lead to serious bleeding: emergency, can give paradoxical clotting

Question 19

contraindications of heparin

Answer 19

thrombocytopenia, bleeding disorders, active peptic ulcer disease, severe htn

Question 20

UF heparin antagonist and when

Answer 20

protamine sulfate. when severe bleeding only. (binds to heparin tightly and inactivates it)

Question 21

LMWH 2 examples

Answer 21

enoxaparin, dalteparin

Question 22

LMWH effect compared to UF heparin

Answer 22

On Xa but not IIa. LMWH catalyze Xa inhib by antithrombin III but not IIa (thrombin) inhibition

Question 23

why LMWH can’t inhib IIa too

Answer 23

lacks tail to bind to IIa too when it’s bound to antithrombin III

Question 24

LMW vs UF heparin effectiveness

Answer 24

same

Question 25

LMWH monitoring

Answer 25

none

Question 26

LMWH effect on aPTT

Answer 26

increased

Question 27

LMWH something better than UF heparin

Answer 27

less incidence of HIT

Question 28

LMWH antagonist

Answer 28

not really. (partial effect only from protamine sulfate)

Question 29

new heparin replacement

Answer 29

fondaparinux (indirect inhibitors of Xa through antithrombin III)

Question 30

fondaparinux: admin, monitoring, HIT risk

Answer 30

s.c once a day, no monitoring, no HIT risk

Question 31

fondaparinux problem

Answer 31

no antagonist

Question 32

2 members of warfarin family

Answer 32

Coumadin (warfarin), sintrom (acenocoumarol)(more in Europe but same)

Question 33

Warfarin and acenocoumarol fct

Answer 33

antagonizes vitamin K and affects synthesis of factors where it is involved

Question 34

factors affected by warfarin and sintrom

Answer 34

II, X, IX, VII

Question 35

warfarin vs heparin: which crosses placenta

Answer 35

warfarin

Question 36

warfarin monitoring how

Answer 36

prothrombin time (PT), now INR

Question 37

INR therapeutic level and why boundaries

Answer 37

2 to 3. minimal therapeutic effect but don'T want bleeding

Question 38

warfarin best for what

Answer 38

prevent stroke in patients with prosthetic heart valves or mitral stenosis

Question 39

2 other uses of warfarin (less now)

Answer 39

prevent DVT above knee + PE complication AFTER HEPARIN TREATMENT prevent stroke if a fib

Question 40

warfarin major toxicity + cause + other toxicity

Answer 40

bleeding. drug interactions. can cross plancenta too

Question 41

warfarin antagonist (how to treat bleeding)

Answer 41

plasma + concentrated K1

Question 42

what type of conditions interact dangeroulsy with warfarin

Answer 42

- bad uptake or metabo of vitK or warfarin - bad synth, fct, clearance of clotting, hemostasis, fibrinolysis factors - bad integrity of epithelia

Question 43

most used new oral anticoag

Answer 43

rivaroxaban

Question 44

dabigatran effect

Answer 44

direct thrombin inhibitor

Question 45

dabigatran used in what

Answer 45

- prevent stroke in non-valvular a fib - prev or treat PE after DVP AFTER OR WITH heparin or LMWH - PE after hip knww replacement

Question 46

dabigatran | inhibitor + fct

Answer 46

idarucizumab, (humanized monoclonal Ab)

Question 47

rivaroxaban effect

Answer 47

direct Xa inhibitor

Question 48

rivaroxaban use

Answer 48

- prev or treat PE, DVT - prevent stroke in a fib - after knee hip replacement

Question 49

new rivaroxaban findings in coronary disease

Answer 49

low dose rivaroxaban + aspirin useful in coronary disease

Question 50

which new anticoagulants don't need start on heparin

Answer 50

rivaroxaban and apixaban

Question 51

apixaban fct

Answer 51

Xa inhibitor

Question 52

edoxaban fct + something to note

Answer 52

like rivaroxaban (Xa inhibitor) but need to start on heparin

Question 53

problem with direct factor Xa inhibitors

Answer 53

no antagonist for now

Question 54

antagonist in dev for Xa inhibitors

Answer 54

Andexanet alfa

Question 55

fibrinolytic drugs effect and why good and bad

Answer 55

catalyse plasmin formation from plasminogen, to lead to lysis of thrombi

Question 56

fibrinolytic drugs main use

Answer 56

acute MI with ST elevation in 6 hrs after infarction if PCI not available

Question 57

danger of fibrinolytic

Answer 57

can lyse physiological thrombi. systemic lytic state