Anti-platelets and anti-thrombotics

Question 1

Name the four stages of haemostasis

Answer 1

Vasoconstriction/vascular spasm –> platelet adhesion, activation, aggregation –> fibrin formation –> network of fibrin

Question 2

Name three groups of anticlotting drugs

Answer 2

Antiplatelet, anti coagulants, thrombolytics

Question 3

Name 4 types of antiplatelets

Answer 3

NSAIDS, platelet GPIIB/IIIA receptor blockers, ADP receptor blockers, PDE inhibitor

Question 4

First event in platelet activation and aggregation

Answer 4

Intact endothelium releases prostacyclin (PGI2) into the plasma, PGI2 binds to platelets and causes them to synthesise cAMP which results in release of granules containing aggregating agents

Question 5

Second event in platelet activation and aggregation

Answer 5

Thrombin, thromboxane A2 and exposed collagen cause release of arachidonic acid from platelet membrane

Thromboxane A2 is synthesized from arachidonic acid and released from the platelet (COX2)

Question 6

Third event in platelet activation and aggregation

Answer 6

Thromboxane A2 binds to receptors on other platelets thereby initiating release of additional aggregating agents

Question 7

Fourth event in platelet activation and aggregation

Answer 7

Balance between levels of prostacyclin and thromboxane A2 influences whether platelet aggregates or circulates freely

Question 8

Name 3 clinical uses of aspirin

Answer 8

Prophylactic treatment of transient cerebral ischemia
reduce the incidence of recurrent myocardial infarction
decrease mortality in post-MI patients

Question 9

2 adverse effects of aspirin

Answer 9

Bleeding (PGI2)

Gastric upset and ulcers (PGE2)
*Gastrointestinal bleeding

Question 10

Name three platelet GP IIB/IIIA blockers

Answer 10

abciximab, eptifibatide, tirofiban

Question 11

Clinical uses of platelet GP iiB/IIIA blockers

Answer 11

prevent restenosis after coronary angioplasty and are used in acute coronary syndromes

Question 12

Name 3 platelet aggregation inhibitors other than direct GP IIB/IIIA blockers

Answer 12

Clopidogrel and ticlopidine (ADP receptor blocker

dipyridamole
(increase intraplatelet cAMP levels)

Question 13

Action of thrombin

Answer 13

1. thrombin (factor IIa) activates upstream proteins, primarily factors V, VIII, and XI, resulting in further thrombin generation
2. cleaves fibrinogen, producing fragments that polymerise to form fibrin
3. activates factor XIII, fibrinoligase, which strengthens fibrin-fibrin links
4. platelet aggregation, cell proliferation and modulates smooth muscle contraction

Question 14

What is antithrombin III?

Answer 14

endogenous anticlotting protein that irreversibly inactivates clotting factor proteases, especially thrombin, IXa and Xa, by forming equimolar stable complexes with them

Question 15

What is the MOA of heparins?

Answer 15

1. active heparin molecules bind to ATIII and cause conformational change –> increase activity
2. to inhibit thrombin –> heparin bind to ATIII and thrombin itself
   to inhibit factor X it only needs to bind to ATIII
3. LMWH increase action of antithrombin III on factor Xa but not on thrombin

Question 16

3 clinical uses of heparin

Answer 16

treatment of DVT, pulmonary embolism, AMI

used with thrombolytics for revascularisation and in combination with GP IIa/IIIB inhibitors during angioplasty and placement of coronary stents

used when an anticoagulant must be used in pregnancy

Question 17

2 adverse effects of heparin

Answer 17

hemorrhage: stop heparin and administer protamine sulfate

thrombosis and thrombocytopenia

Question 18

How is heparin administered

Answer 18

IV/SC, IM for hematomas

Question 19

2 clinical uses of vitamin K

Answer 19

treatment and or prevention of bleeding
–> from use of oral anticoagulant
–> in babies, prevent hemorrhagic disease in newborn

for vitamin K deficiency in adult

Question 20

Warfarin MOA?

Answer 20

Inhibit vitamin K reductase

Question 21

What is warfarin contraindicated in?

Answer 21

Pregnant women

Question 22

name 2 adverse effects of warfarin

Answer 22

bleeding

never administer to pregnant women
- crosses placenta readily, cause hemorrhagic disorder in the fetus

• fetal proteins wiht gamma-carboxyglutamate residues found in bone and blood may be affected by warfarin

Question 23

Elimination of warfarin from the body?

Answer 23

metabolism by hepatic cytochrome p450

ddi with other p450 drugs

barbiturates, carbamazepine, phenytoin

amiodarone, cimetidine, disulfiram, imipramine

Question 24

Name 4 types of thrombolytic agents

Answer 24

t-PA, urokinase, streptokinase, anistreplase

Question 25

moa of thrombolytic agents

Answer 25

increase conversion of plasminogen to plasmin

Question 26

3 clinical uses of thrombolytic agents

Answer 26

emergency treatment of coronary artery thrombosis

peripheral arterial thrombosis and emboli

ischaemic stroke (<4.5 hour window)

Question 27

Administration of thrombolytics?

Answer 27

Intracoronary injection, IV

Question 28

1 adverse effect and 2 contraindications

Answer 28

A: bleeding
C: healing wound, pregnancy

Question 29

Administration of warfarin

Answer 29

Oral