Pharmacology Exam 3

Front 1

What does fibrinogen bind to?

Back 1

GPIIb/IIIa

Front 2

How do platelets aggregate?

Back 2

By binding to fibrinogen

Front 3

These (5) things require vitamin K for their synthesis

Back 3

1- VII
2- IX
3- X
4- Prothrombin (II)
5- Activated protein C

Front 4

__ cross-links platelets while __ forms clots.

Back 4

Fibrinogen; fibrin

Front 5

This factor stabilized clots

Back 5

XIIIa

Front 6

Thrombin activates these (5) things

Back 6

1- Platelets
2- VII
3- VIII
4- XIII
5- Fibrinogen --> fibrin

Front 7

What does plasmin do?

Back 7

Breaks up clots

Front 8

What does antithrombin III do?

Back 8

Decreases activation of thrombin and factors IX, X, XI, XII

Front 9

Factors Va and VIIa are degraded by what?

Back 9

Activated protein C

Front 10

The clotting cascade

Back 10

12 -> 11 -> 9 -> 10 -> prothrombin (2) -> thrombin -> fibrinogen -> fibrin

Front 11

IXa activates __ and __. VIIa activates __.

Back 11

VIII and X; X

Front 12

White thrombi

Back 12

- Thrombus in the arteries
- Fibrin + platelets
- Atherosclerotic plaque
- Can cause tissue damage by restricted blood flow

Front 13

Red thrombi

Back 13

- Thrombus in the veins
- Fibrin + RBC
- Swelling and edema
- Can cause tissue damage by restricted blood flow

Front 14

Thromboembolus

Back 14

A broken off thrombus

Front 15

Conditions under which anticoagulants are used (4)

Back 15

1) Thromboembolic diseases: thrombophlebitis, pulmonary embolism; inc likelihood of a stroke
2) After most kinds of surgery, especially abdominal
3) During transfusions
4) In Px w/ heart diease: CHF, MI, valve replacement

Front 16

Calcium chelators

Back 16

- EGTA, EDTA, citric acid
- Keeps blood from clotting
- Not used in-vitro

Front 17

Location and properties of heparin

Back 17

- Located in mast cells
- Strong negative charge
- Mixture of high and low molecular weight polymers

Front 18

Physiological effects of heparin

Back 18

- Inhibits clotting in-vitro and in-vivo
- Activates lipoprotein lipase

Front 19

Heparin mechanism of action

Back 19

- Activates the enzyme antithrombin III by a factor of 1000
- Low doses: inhibits Xa
- High doses: inhibits thrombin

Front 20

T/F Heparin can lyse existing clots

Back 20

False, it cannot

Front 21

Pharmacokinetics of heparin

Back 21

- Too large and too negatively charged for oral absorption
- Given IV or subcutaneously
- Doesn't cross placenta
- T.5 = 1 hour

Front 22

Heparin toxicity

Back 22

- Bleeding due to overdose
- Long term: Osteoporosis (osteoclasts), thrombocytopenia (HIT), platelet heparin complex bound to antibodies

Front 23

This is used to Tx heparin overdose

Back 23

Protamine sulfate
- comes from salmon sperm

Front 24

Enoxaparin, dalteparin, tinzaparin

Back 24

- Low M.W. heparins
- T.5 = 4hrs
- Greater effect on Xa
- Less thrombocytopenia and osteoporosis
- Overdose can't be treated w/ protamine sulfate
- SE: spinal hematoma in Px after spinal tap

Front 25

Fondaparinux

Back 25

- Synthetic heparin analog
- Acts only on Xa
- Longer half life
- Can cross the placenta

Front 26

Hirudin

Back 26

An anticoagulant found in leech saliva; it binds to an inactivates thrombin

Front 27

Lepirudin, bivalirudin, desirudin, argatroban

Back 27

- Given IV or subcutaneously
- Don't cause HIT or osteoporosis

Front 28

First oral anticoagulant

Back 28

Warafin (Coumadin)

Front 29

Warafin's mechanism of action

Back 29

- Vitamin K analog
- Inhibits the synthesis of VII, IX, X, and prothrombin
- Can prevent clotting but can't remove exhausting clots

Front 30

Half lives of factors VII, IX, X, prothrombin

Back 30

6, 24, 40, 60 hours

Front 31

Pharmacokinetics of warafin

Back 31

- Metabolized by P450
- A diet high in vitamin K inhibits warafin
- Other drugs can also increase the [ ]

Front 32

Warafin toxicity

Back 32

- Excessive bleeding
- Can pass through the placenta => category X
- Small thrombin in peripheral vasculature, "purple toe syndrome"
- Tx overdose w/ lots of vitamin K

Front 33

Dabigatran

Back 33

- Direct thrombin inhibitor
- Given orally
- Prodrug
- SE: some GI effects, safer than warafin

Front 34

Factor Xa inhibitor (1)

Back 34

Rivaroxaban
- Deep venous thrombosis
- SE: bleeding and spinal hematoma

Front 35

COX Inhibitor (1)
(Enzyme inhibitor)

Back 35

1) Asprin
- Inhibits the formation of thromboxane A2 => dec platelet aggregation

Front 36

Phosphodiesterase Inhibitors (2)

Back 36

1) Cilostazol
2) Dipyridamole

- Increase the concentration of cAMP

Front 37

ADP Inhibitors (3)
(Irreversible blockers of platelet ADP receptors)

Back 37

1) Ticlopidine: SE include neutropenia, agranulocytosis, thrombocytopenia
2) Clopidogrel
3) Prasugrel

- All prodrugs

Front 38

Reversible ADP receptor blocker (1)

Back 38

Ticagrelor
- Faster and shorter duration than the irreversible blockers

Front 39

Fibrinogen receptor inhibitors (3)

Back 39

- Block GP IIb/IIIa receptors on platelets => dec platelet aggregation
- Given IV and can cause thrombocytopenia

1) Abciximab: monoclonal antibody
2) Tirofiban: non-peptide
3) Eptifibatide: peptide

Front 40

Platelet counter reducer (1)

Back 40

Anagrelide
- Decreases the number of platelets in circulation

Front 41

Contraindications for all anticoagulants

Back 41

Bleeding disorders, severe hypertension, and after surgery(eye, brain, spinal cord)

Front 42

Agents that dissolve formed clots (2)

Back 42

1) Streptokinase and urokinase: convert plasminogen to plasmin; plasmin hydrolysis fibrin and degrades fibrinogen
2) Tissue plasminogen activator

Front 43

Hemostatic agents (2)
(enzyme inhibitors)

Back 43

1) Aminocaproic acid: inhibits plasminogen activation
2) Tranexamic acid: more potent

Front 44

Astringents

Back 44

- Metal salts that precipitate proteins
- May act as desiccants
- Ex: aluminum chloride, zinc chloride, ferrous sulfate