anti clotting drugs

Question 1

classes of drugs for anti clotting

Answer 1

1. antiplatelet
2. anticoagulants
3. thrombolytics

Question 2

name the 4 antiplatelet drugs

Answer 2

1. aspirin
2. GP2b/3a receptor blockers
3. ADP receptor blockers
4. PDE inhibitors

Question 3

which prostanoids are heavily involved in primary hemostasis

Answer 3

PGI2 (anti thrombotic)

TXA2 (pro thrombotic)

Question 4

what does PGI2 do in primary hemostasis

Answer 4

1. helathy intact endothelium release PGI2 into plasma
2. PGI2 blinds to platelet membrane receptors –> conversion of ATP to cAMP
3. cAMP inhibits release of granules containing aggregating agents (serotonin, ADP)

Question 5

what does TXA2 do in primary hemostasis

Answer 5

1. thrombin + TXA2 + subendothelial collagen cause release of arachidonic acid from platelet membrane
2. TXA2 is synthesised from archidonic acid in platelet, then released
3. TXA2 binds to receptors on other platelets, inititaes release of additional aggregating agents (serotonin, ADP)

Question 6

aspirin MOA

Answer 6

1. irreversible nonselective COX inhibitor –> no production of prostanoids from arachidonic acid
2. antiplatelet effect as PGI2 can be restored, TXA2 cannot
   => overall antiplatelet effect

Question 7

aspirin PK

Answer 7

rapid inhibitory effect that lasts for the platelet lifespan (7-10 days) as it is irreversible inhibitor

Question 8

aspirin clinical uses

Answer 8

1. prophylactic treatment of transient cerebral ischemia (BUT recent studies indicate against use if there is no history of cerebral infarct, MI, etc.)
2. reduce incidence of recurrent MI
3. decrease mortality in post MI patients

Question 9

aspirin adverse effects

Answer 9

1. gastic upset and ulcers

Question 10

what do gp2b/3a receptors do in primary hemostasis

Answer 10

for platelet aggregation

1. for fibrinogen and vitrionectin binding - cross link platelets
2. for fibronectin and vWF binding
3. activation of this receptor is final common pathway for platelet aggregation

Question 11

name 3 gp2b/3a receptors blockers

Answer 11

abciximab, eptifibatide, tirofiban

Question 12

gp 2b/3a receptor blockers MOA

Answer 12

displace fibrinogen that is cross linking platelets on existing thrombi –> prevent further platelet cross linking and thrombosis

=> prevents clot formation

Question 13

how does abciximab displace fibrinogen

Answer 13

humanised Ab that reversibly inhibits binding of fibrinogen and other ligands

Question 14

how does eptifibatide displace fibrinogen

Answer 14

analog of sequence at C terminal of delta chain of fibrinogen, which mediates binding of fibrinogen to receptor
thus preventing binding between fibrinogen and receptor

Question 15

how does tirofiban displace fibrinogen

Answer 15

tirofiban is a small molecule receptor blocker

Question 16

gp 2b/3a receptor blocker clinical uses

Answer 16

1. prevent restenosis after coronary angioplasty

2. acute coronary syndromes (to prevent possible thrombus formation)

Question 17

name 2 ADP receptor blockers

Answer 17

clopidogrel, ticlopidine

Question 18

ADP receptor blocker MOA

Answer 18

prevent binding of ADP to ADP receptors –> reduce platelet aggregation

Question 19

name 1 PDE inhibitor

Answer 19

dipyridamole

Question 20

PDE inhibitor MOA

Answer 20

prevent conversion of cAMP to 5’AMP –> accumulation of cAMP –> inhibits release of granules containing aggregating agents (serotonin, ADP)

Question 21

what are the main anticoagulants

Answer 21

1. heparin
2. warfarin (coumarin derivative)
3. lepirudin and hirudin

Question 22

what does thrombin do in hemostasis

Answer 22

1. activates upstream factors esp 5, 8, 11
2. cleaves fibrinogen to form fragments that polymersise to form fibrin
3. 8 is a fibrinoligase that strengthens fibrin-fibrin cross links, stabilising coagulum
4. causes platelet aggregation, stimulate cell proliferation, modulates SM contraction

Question 23

what does antithrombin III do

Answer 23

is an endogenous anticlotting protein:

irreversibly inactivates factors 2, 9, 10, (11, 12) by forming equimolar stable complexes

Question 24

what are heparins

Answer 24

a family of sulfated glycosaminoglycans

Question 25

heparin MOA

Answer 25

1. bind to ATIII --> conformational change that exposes its active sites for more rapid interaction with factors (proteases) - inhibtion of thrombin: heparin needs to bind both thrombin and ATIII - inhibition of 10: heparin binding to ATIII alone is enough

Question 26

what is the difference between LMWH and normal heparin

Answer 26

LMWH increases action of ATIII on factor 10 but not its action on thrombin LMWH has longer doa than regular heparin

Question 27

heparin PK

Answer 27

IV or SC administration

Question 28

can heparin be given IM?

Answer 28

No. will result in hematomas

Question 29

heparin clinical uses

Answer 29

1. DVT, PE, MI - use together with thrombolytics for revascularisation (heparin is just anticoagulant, wont do anything against thrombi that have already formed) 2. angioplasty and placement of coronary stents (use together with GP2b/3a inhibitors) 3. if anticoagulant must be used in pregnancy

Question 30

which drug combination is used for thrombotic events

Answer 30

heparin/warfarin and thrombolytics

Question 31

which drug combination is used for angioplasty and coronary stents

Answer 31

heparin/warfarin and GP2b/3a inhibitors

Question 32

which anticoagulant is still safe to use in pregnancy

Answer 32

heparin

Question 33

heparin adverse effects

Answer 33

1. hemorrhage --> stop heparin therapy, give protamine sulfate (binds and inhibits heparin) 2. thrombosis 3. thrombocytopenia

Question 34

how can heparin cause thrombosis

Answer 34

platelet factor 4:heparin complex can form immune complexes with IgM/IgG --> activate platelets, more relase PF4 --> cause endothelial damage with antibodies

Question 35

warfarin MOA

Answer 35

inhibits vit K reductase --> cannot regenerate reduced Vit K which is needed for carboxylation of glutamic acid --> cannot produce functional factors 2, 7, 9, 10

Question 36

warfarin PK

Answer 36

oral, absorbed quickly small Vd, strongly bound to albumin metabolised by hepatic CYP450 (DDIs!)

Question 37

warfarin clinical uses

Answer 37

1. DVT, PE, MI - use together with thrombolytics for revascularisation (heparin is just anticoagulant, wont do anything against thrombi that have already formed) 2. angioplasty and placement of coronary stents (use together with GP2b/3a inhibitors)

Question 38

warfarin adverse effects

Answer 38

bleeding

Question 39

warfarin contraindications

Answer 39

pregnancy - crosses placenta --> hemorrhagic disorder in fetus - fetal proteins with gamma-carboxyglutamate residues found in bone and blood get affected

Question 40

how to reverse effects of warfarin?

Answer 40

give reduced vit K (can prevent hemorrhagic disease of newborn)

Question 41

what are thrombolytics

Answer 41

plasminogen activators

Question 42

name 4 thrombolytics

Answer 42

alteplase (tPA), urokinase, streptokinase, anistreplase

Question 43

thrombolytics MOA

Answer 43

convert plasminogen to plasmin - main: plasmin breaks down fibrin to fibrin degradation products - plasmin breaks fown fibrinogen to fibrinogen degradation products

Question 44

thrombolytics administration

Answer 44

intracoronary injection, IV

Question 45

thrombolytics clinical uses

Answer 45

1. emergency treatment of coronary artery thrombosis (can use with anticoagulants) 2. peripheral arterial thrombosis and emboli

Question 46

thrombolytics adverse effects

Answer 46

bleeding

Question 47

thrombolytics contraindications

Answer 47

pregnancy, presence of healing wound