Agents that affect the clotting system

Question 1

what clotting factors require vitamin k for synthesis?

Answer 1

IX, VII, X, Prothrombin (II)

Question 2

what clotting factors require calcium to be activated?

Answer 2

XI, X, Prothrombin (II), Fibrinogen, XIII

Question 3

how is clot formation reversed?

Answer 3

via plasminogen being activated into plasmin causing clot lysis

Question 4

what does thrombin do?

Answer 4

activates platelets, factors VII, VIII, XIII

Question 5

what does fibrinogen do?

Answer 5

cross link platelets

Question 6

what does fibrin do?

Answer 6

forms clot

Question 7

how is clot localized?

Answer 7

antithrombin III causes inactivation of thrombin, factors IX, X, XI, XII

Question 8

what disorder is inadequate clotting?

Answer 8

hemophilia

Question 9

what is thrombus?

Answer 9

clot that adheres to BV wall

Question 10

what are white thrombi?

Answer 10

in arteries
associated with artherosclerotic plaques
platelet and fibrin strands
ischemic damage to tissues whose blood supply was compromised

Question 11

what aure red thrombi?

Answer 11

in veins
associated with pooling of blood in extremities
RBC+fibrin
ischemic damage to tissues whose blood supply was compromised

Question 12

what is thromboembolus?

Answer 12

piece of thrombus breaks off and travels through blood stream

Question 13

what are the conditions for which anticoagulants are used?

Answer 13

thromboembolic diseases, after most kinds of surgery, during transfusions, in px with heart disease

Question 14

tell me about calcium chelators

Answer 14

citric acid, EDTA, EGTA,
all chelate calcium
all work in vitro

Question 15

tell me about the location and properties of heparin

Answer 15

located in mast cells
strong negative charge
prepared from cow lung and pig intestines
mixture of high and low molecular weight polymer
not synthetic- every batch must be individually tested for activity

Question 16

what are the physiological effects of heparin

Answer 16

inhibits clotting in vivo and in vitro

activates enzymes lipoprotein lipases in blood

Question 17

what is heparin’s mechanism of action

Answer 17

binds to antithrombin (a protease inhibitor) and increase its affinity for clotting factors by 1000x
heparin does not lyse existing clot

Question 18

what does heparin help antithrombin inhibit at low doses

Answer 18

inhibit factor Xa- decreases formation of thrombin

Question 19

what does heparin help antithrombin inhibit at high doses

Answer 19

inhibits thrombin and IXa, XIa, XIIa

Question 20

how is heparin administered?

Answer 20

given by injection- TV or subq- too large to be absorbed by guts

Question 21

can heparin pass the placenta?

Answer 21

no too large

Question 22

how quick does heparin work?

Answer 22

immediate onset of action

t1/2=1hr

Question 23

what is heparin degraded by?

Answer 23

heparinase in body

Question 24

what kind of dose response does heparin have?

Answer 24

unpredictable dose response

Question 25

toxicity of heparin? long term use?

Answer 25

major damage is bleeding long term use- osteoporosis- due to osteoclast stimulation thrombocytopenia- heparin induced thrombocytopenia hypersensitivity

Question 26

what is heparin overdosed treated with?

Answer 26

protanine sulfate

Question 27

what are the low molecular weight heparins?

Answer 27

enoxaparin | dalteparin

Question 28

tell me about enoxaparin and dalteparin

Answer 28

partially purified heparin longer t1/2- 4hours more effect on Xa than on thrombin less osteoporosis and HIT more predictable dose response more expensive - not readily reversed by protamine may cause spinal hematoma in pt who have had spinal tap/anesthesia

Question 29

tell me about fondaparinux

Answer 29

``` heparin like drugs purely synthetic t1/2=17 hours acts only on factor Xa can cross placenta can't bind protamine ```

Question 30

what is derived from leeches and how does it function

Answer 30

hirudin- anticoagulant in leech saliva directly inhibiting thrombin enzyme inhibitor

Question 31

what drugs are related to hirudin? when are they used?

Answer 31

bivalirudin desirudin argatroban used when pt has heparin induced thrombocytopenia

Question 32

what is the oral anticoagulant

Answer 32

warfarin

Question 33

warfarin mechanism

Answer 33

vitamin k analog vitamin k is essential for synthesis of factors VII, IX, X, Prothrombin works by inhibiting the enzymes that allow vitamin k to be recycled recycling is inhibited and thus vitamin k deficiency

Question 34

what is warfarin's initial onset?

Answer 34

24+ hours

Question 35

how is warfarin metabolized?

Answer 35

by metabolizing by p450- any drug that affect p450 can affect the concentration of warfarin

Question 36

what is the toxicity of warfarin?

Answer 36

hemorrhage | can pass placenta-> pregnancy category X

Question 37

what is the direct thrombin inhibitor?

Answer 37

dabigatran

Question 38

what is dabigatran?

Answer 38

prodrug- inhibits the enzyme thrombin | works within an hour

Question 39

what is the side effect of dabigatran?

Answer 39

se: hemorrhage

Question 40

what are the factor Xa inhibitors?

Answer 40

rivaroxaban apixaban rapid onset

Question 41

what are the side effects of rivaroxaban and apixaban?

Answer 41

bleeding after spinal tap or spinal surgery

Question 42

what are the platelet inhibitors?

Answer 42

``` thrombin receptor blocker adp inhibitors fibrinogen inhibitors COX inhibitors phosphodiesterase inhibitors platelet count reducer ```

Question 43

what is the thrombin receptor blocker?

Answer 43

vorapaxar

Question 44

how does vorapaxar work?

Answer 44

blocks the platelet thrombin receptor

Question 45

who should be cautious of vorapaxar

Answer 45

use carefully in px with history of intracranial bleeding

Question 46

what are the adp inhibitors?

Answer 46

ticlopidine clopidogrel prasugrel ticagrelor

Question 47

how does ticlopidine, clopidogrel, prasugrel, ticagrelor work?

Answer 47

adp receptor blockers- inhibit adp binding to platelet inhibitors

Question 48

what is the side effect of ticlopidine

Answer 48

neutropenia, agranulocytosis

Question 49

how are clopidogrel, prasugrel, ticagrelor different?

Answer 49

difference is in pharmacokinetics

Question 50

what are the fibrinogen receptor inhibitors?

Answer 50

abciximab tirofiban eptifibatide

Question 51

how do abciximab, tirofiban, eptifibatide work?

Answer 51

all prevent platelet aggregation | all given iv

Question 52

what can abciximab, tirofiban, eptifibatide cause?

Answer 52

thrombocytopenia

Question 53

what kind of molecule is abciximab?

Answer 53

monoclonal antibody vs. receptors

Question 54

what is the COX inhibitor?

Answer 54

aspirin

Question 55

how does aspirin work?

Answer 55

inhibit TXA2 synthesis (cyclooxygenase inhibitor)- decreases platelet aggregation

Question 56

what are the phosphodiesterase inhibitors?

Answer 56

cilostazol, dipyridamole

Question 57

mechanism of cilostazol and dipyridamole

Answer 57

inhibits the enzyme that breaks down cAMP

Question 58

what is the plate count reducer?

Answer 58

anagrelide

Question 59

mechanism of anagrelide

Answer 59

decrease platelet formation, maturation and number

Question 60

what are the contraindications for all anticoagulants?

Answer 60

bleeding disorder- bleeding in GI tract severe hypertension after surgery in eye, brain, spinal cord

Question 61

what are the thrombolytic agents (agents that dissolve formed clots)?

Answer 61

streptokinase urokinase tissue plasminogen activator

Question 62

what are the mechanisms of streptokinase, urokinase, tissue plasminogen activator?

Answer 62

``` all are enzymes all given IV all convert plasminogen to plasmin plasmin hydrolyzes fibrin plasmin degrades fibrinogen and factors V and VII ```

Question 63

what are the hemostatic agents? what do hemostatic agents do?

Answer 63

aminocaproic acid and tranexamic acid enhance clotting

Question 64

how do aminocaproic acid and tranexamic acid work?

Answer 64

inhibits plasmnogen activation- enzyme inhibitor