Week 5 Pharmacology

Question 1

How does Heparin work?

Answer 1

Induces antithrombin
–> accelerates inhibition of thrombin and Factor Xa

Heparin has binding sites for both antithrombin and thrombin.
Thrombin cleaves part of antithrombin which causes antithrombin to wrap around and inhibit thrombin.

Question 2

How do coumarol drugs work?

Answer 2

Inhibit reduction of Vit K in liver.

Vit K

Question 3

What cleaves fibrin?

Answer 3

Plasmin

Question 4

What holds fibrin together?

Answer 4

Covalent and non-covalent bonds.

Question 5

Fibrin is crosslinked by what?

Answer 5

Factor XIIIa

Question 6

What are fibrinopeptides?

Answer 6

Peptides released from the alpha and beta chains of fibrinogen. This allows for the terminal ends to now bind to other fibrin monomers.

Question 7

What are D2E fragments?

Answer 7

Products resulting from plasmin breaking down of fibrin.

Elevated with liver disease.

Question 8

How does the body respond to blood vessel injury?

Answer 8

Platelets aggregate at injury site

• -> platelets are activated
• -> platelets release granules
• -> extrinsic clotting cascade begins

Question 9

What is Protein C?

Answer 9

Vitamin K-dependent plasma protein anticoagulant

• aka. Clotting Factor XIV (xymogen)
• plays a role in preventing clotting, inflammation, cell death, and permeability of capillary membrane

Question 10

What happens in Protein C deficiency?

Answer 10

Blood tends to clot more
ex. DVT
Risk of recurrent thrombotic diseases

Question 11

How does warfarin effect Protein C?

Answer 11

Warfarin decreases the anticoagulant activity of Protein C.

Question 12

What activates Protein C?

Answer 12

Thrombin

Question 13

What is serum?

Answer 13

The liquid portion of blood that is leftover after the blood has been allowed to clot.
Therefore does not contain clotting factors.

Question 14

Name some chelating agents.

Answer 14

Citrate

EDTA

Question 15

What do chelating agents do?

Answer 15

Removes Calcium from Gla proteins in blood.

Prevents clotting!

Question 16

What does thrombomodulin do?

Answer 16

Changes the substrate specificity of Thrombin
Thrombin-thrombomodulin complex activates Protein C.
–> Inactivates Factor Va, VIIIa
–> Fibrin production is inactivated
–> Anticoagulant activity

Question 17

What is thrombin?

Answer 17

A pro-coagulant

Question 18

What does thrombin do?

Answer 18

Converts fibrinogen to fibrin.
Activates platelets, Factor V, VIII, (XI), & XIII
Activates Protein C

Question 19

What is standard treatment of DVT and PE?

Answer 19

Anticoagulant therapy.

Question 20

What are some typical clinical features of PE?

Answer 20

Dyspnea
Pleuritic pain
Hemoptysis
Loud P2 Heart sound
Rigors

Question 21

What increases the likelihood of peripheral venous thrombosis?

Answer 21

Virchow’s Triad:

• Stasis
• Hypercoagulability
• Endothelial damage

Polycythemia
Oral contraceptives
Dehydration

Question 22

What is the most common heart rhythm in pts with PE?

Answer 22

Sinus tachycardia

Question 23

Is hemoptysis associated with pneumonia?

Answer 23

No; very rarely.

Question 24

Compare fibrinolytic therapy to heparin.

Answer 24

Fibrinolytic Therapay:

• more expensive
• more likely to bleed
• more rapid decrease in pulm HTN for large PE

Question 25

After PE, what is the typical length of time that warfarin (coumadin) is given for?

Answer 25

3-6 months

Question 26

How long does it take for PE's to dissolve?

Answer 26

Days to weeks after starting on anticoagulation Tx.

Question 27

What are some targets for anticoagulation?

Answer 27

1. Anti-platelet 2. Chelate Ca++ 3. Inhibit carbox'n of Gla proteins 4. Anti-thrombin 5. Directly inhibit thrombin 6. Thrombolytic agent

Question 28

Name examples and describe anti-platelet agents.

Answer 28

ASA - inhibits COX - prevents synthesis of TXA2 - prevents platelet activation and aggregation

Question 29

Coumarol drugs are also know as... Name one.

Answer 29

blood thinners ex. Warfarin

Question 30

What are couramol drugs used for? | How are they administered?

Answer 30

Long-term anti-coagulation in thrombosis-risk pts. | Can be taken orally (100% bioavailability)

Question 31

How can the action of coumarol be reversed?

Answer 31

Additional Vit K intake | Therefore must monitor INR continuously

Question 32

What is INR?

Answer 32

INR = [ Prothrombin(test) / Prothrombin(control) ] ^ ISI

Question 33

How does warfarin affect PT (prothrombin time)?

Answer 33

Warfarin prolongs prothrombin time.

Question 34

When is warfarin indicated?

Answer 34

- prophylaxis and Tx of VTE - prophylaxis and Tx of atrial fib - valvular stenosis - heart valve replacement - MI - Antiphospholipid syndrome

Question 35

Name some Gla proteins. Which has the longest half-life? shortest?

Answer 35

Prothrombin --> longest half-life Factor VII --> shortest half-life Factor IX Factor X

Question 36

What initiates the extrinsic pathway?

Answer 36

External damage to blood vessel - -> releases Tissue Factor - -> binds to Factor VIIa

Question 37

What converts prothrombin to thrombin?

Answer 37

Factor Xa and Factor Va

Question 38

Why does warfarin need to be monitored so closely?

Answer 38

Narrow therapeutic index Can increase risk of bleeding Effectiveness altered by diet

Question 39

How is warfarin use monitored?

Answer 39

INR and PT

Question 40

What is the target INR for someone with previous VTE?

Answer 40

Target INR range: 2.0 - 3.0

Question 41

What does an INR < 2 suggest?

Answer 41

Increased risk of thromboembolism (& stroke & MI)

Question 42

What does an INR > 4.5 suggest?

Answer 42

Increased risk of bleeding

Question 43

What is a serpin?

Answer 43

SERPIN = SERine Protease INhibitor ex. antithrombin

Question 44

What is PTT? | What does it measure?

Answer 44

PTT = Partial Prothromboplastin Time | Measures clotting factors in pt who is taking Heparin

Question 45

How does size of the Heparin chain affect fxn?

Answer 45

Factor Xa can be inhibited (via antithrombin) with any size Heparin chain. Thrombin can be inhibited (via antithrombin) ONLY with Heparin chain > 18 sugars.

Question 46

What are some advantages of LMWH over UFH?

Answer 46

- Decreased Heparin resistance - Don't need lab monitoring - Higher bioavailability (90% vs 30%) - Longer plasma half-life (4-6 hrs vs 0.5-1 hr) - Less inhibition of platelet fxn - Lower incidence of thrombocytopenia and thrombosis - Less interaction with platelet factor 4

Question 47

How is Heparin administered?

Answer 47

IV | - Must be injected becuase it is highly charged.

Question 48

How can Heparin action be reversed?

Answer 48

Administration of protamine sulfate | protein that forms a complex with Heparin

Question 49

What is a serious risk of Heparin?

Answer 49

Fatal thrombocytopenia

Question 50

What is a type of synthetic Heparin?

Answer 50

Fondaparinux

Question 51

What agent directly inhibits Factor Xa?

Answer 51

Rivaroxaban

Question 52

What agent directly inhibits Thrombin?

Answer 52

Dabigatran

Question 53

How can the action of direct Thrombin/Factor Xa inhibition be reversed?

Answer 53

It can't. | There's no known antidote.

Question 54

What is an advantage of direct Thrombin/Factor Xa inhibitors?

Answer 54

Patient does not require close monitoring.

Question 55

How do Thrombolytic agents work?

Answer 55

Activate plasminogen to plasmin

Question 56

How are Thrombolytic agents administered?

Answer 56

IV

Question 57

What are some examples of thrombolytic agents?

Answer 57

Urokinase Streptokinase (bacterial) Tissue Plasminogen Activator "TPA" (recombinant)

Question 58

What are thrombolytic agents indicated for?

Answer 58

Ischaemic stroke caused by blood clot