Antiplatelets and Antithrombotics

Question 1

Name 3 classes of anti clotting drugs

Answer 1

1. Antiplatelets
2. Anticoagulants
3. Thrombolytics

Question 2

Name 4 classes of antiplatelets

Answer 2

1. NSAIDs
2. Platelet GPIIB/IIIA receptor blockers
3. ADP receptor blockers
4. Phosphodiesterase (PDE) inhibitors

Question 3

Name an example of a NSAID antiplatelet

Answer 3

Aspirin

Question 4

Name 3 examples of platelet GPIIB/IIIA receptor blockers

Answer 4

1. Abciximab
2. Tirofiban
3. Eptifibatide

Question 5

Name 2 examples of ADP receptor blockers

Answer 5

1. Ticlopidine
2. Clopidogrel

Question 6

Name a PDE inhibitor

Answer 6

Dipyridamole

Question 7

MOA of aspirin

Answer 7

COX 1 and COX 2 inhibitor, which reduces conversion of arachidonic acid to eicosanoids. Acts as an anti platelet

Question 8

3 clinical uses of aspirin

Answer 8

1. Prophylactic treatment for transient cerebral ischemia
2. Reduce the incidence of recurrent myocardial infarction
3. Decrease mortality in patients with post myocardial infarction

Question 9

2 ADRs of aspirin use

Answer 9

1. Bleeding (PGI2)
2. GI effects: gastric upset, ulcers, GI bleeding (PGE2)

Question 10

State the normal function of GPIIb/IIIa receptor

Answer 10

A platelet membrane surface protein.
GPIIb/IIIa complex functions as a receptor for mainly fibrinogen and vitronectin, and also fibronectin and vWF.
Activation of the complex is the final common pathway for platelet aggregation

Question 11

Structure of abciximab

Answer 11

Chimeric monoclonal antibody that reversibly inhibits the GPIIb/IIIa receptor complex

Question 12

Structure of eptifibatide

Answer 12

Structural analogue of the carboxyl terminal of fibrinogen, thus binds reversibly to the GPIIb/IIIa receptor complex

Question 13

2 clinical uses of platelet GPIIb/IIIa receptor blockers

Answer 13

1. Prevent restenosis after coronary angioplasty
2. Treatment of acute coronary syndrome

Question 14

MOA of clopidogrel and ticlopidine

Answer 14

ADP receptor inhibitor. Prevent binding of ADP, reduce platelet aggregation

Question 15

MOA of dipyridamole

Answer 15

Inhibits PDE which prevents conversion of cAMP to AMP, thus reducing platelet aggregation

Question 16

Name the 4 drug classes for anticoagulants

Answer 16

1. Heparin derivatives
2. Coumarin derivatives (Warfarin)
3. Lepirudin, Hirudin
4. Antithrombin III

Question 17

Outline 4 physiological actions / effects of thrombin

Answer 17

1. Activates upstream proteins (esp factor V, VIII and XI) which increases thrombin generation
2. Cleaves fibrinogen into fibrin which polymerises
3. Activates factor XIII to factor XIIIa which stabilises the fibrin-fibrin linkages
4. Increases platelet aggregation, stimulates smooth muscle contraction and increases cell proliferation

Question 18

MOA of antithrombin III

Answer 18

Endogenous anticlotting protein that irreversibly binds and inactivates clotting factor proteases, especially IIa (thrombin), IXa and Xa by forming equilimolar stable complexes with them

Question 19

Heparin is a family of sulfated…

Answer 19

Glycosaminoglycans

Question 20

State 2 PK advantages of low molecular weight heparin (LMWH) compared to regular heparin

Answer 20

1. Higher bioavailability
2. Longer half-life

Question 21

MOA of heparin on factor IIa (thrombin)

Answer 21

Binds tightly to ATIII, causing a conformational change which exposes its active site for more rapid interaction with the protease
Must bind to BOTH ATIII and factor IIa to inhibit thrombin

Question 22

MOA of heparin on factor Xa

Answer 22

Binds tightly to ATIII, causing a conformational change which exposes its active site for more rapid interaction with the protease
Only needs to bind to ATIII to inhibit factor Xa

Question 23

LMWHs increase the action of ATIII on factor ___ but not on factor ___

Answer 23

Increase action on factor Xa but not on factor IIa

Question 24

State 4 clinical uses of heparin

Answer 24

1. Treatment of DVT, pulmonary embolism, acute myocardial infarction
2. Combine with thrombolytics for revascularisation
3. Combine with GPIIb/IIIa blockers during angioplasty and inserting coronary stents
4. Used as an anticoagulant in certain pregnancies for treating venous thromboembolism (VTE)

Question 25

Is heparin / LMWH safe to use in pregnant patients?

Answer 25

Yes

Question 26

2 routes of administration for heparin

Answer 26

1. Intravenous 2. Subcutaneous

Question 27

Heparin must NEVER be administered ___ as it can cause ___

Answer 27

Intramuscularly Hematomas

Question 28

State 2 ADRs of heparin use

Answer 28

1. Haemorrhage 2. Thrombocytopenia

Question 29

Outline the treatment for heparin induced haemorrhage

Answer 29

Stop heparin therapy Give protamine sulfate (cationic peptide): Forms an inactive ionic complex with heparin

Question 30

Name the 4 clotting factors that require vitamin K

Answer 30

Factors II, VII, IX, X

Question 31

Functioning / activated vitamin K needs to be in the reduced or oxidised state?

Answer 31

Reduced state

Question 32

Name the enzyme that reduces oxidised vitamin K into its reduced form

Answer 32

Vitamin K reductase

Question 33

Name the type of reaction that reduced vitamin K is used in activating factors II, VII, IX, X

Answer 33

Carboxylation of glutamate residues in clotting factors

Question 34

State 3 clinical uses of vitamin K

Answer 34

1. Treatment and prevention of bleeding from the use of oral anticoagulants 2. Babies: Used to prevent haemorrhagic disease of the newborn 3. Adults: For patients with vitamin K deficiency

Question 35

MOA of warfarin

Answer 35

Vitamin K reductase inhibitor. Inhibits the reduction of oxidised vitamin K, thus reduces the carboxylation of glutamate residues in clotting factors II, VII, IX, X, thus inhibiting their coagulation function

Question 36

State 3 clinical uses of warfarin

Answer 36

*same as heparin 1. Treat DVT, PE, AMI 2. Combine with thrombolytics for revascularisation 3. Combine with GPIIb/IIIa during angioplasty and for inserting coronary stents

Question 37

Warfarin is administered

Answer 37

Orally

Question 38

Does warfarin bind to albumin in the blood?

Answer 38

Yes

Question 39

Where is warfarin metabolised?

Answer 39

Liver by CYP450

Question 40

State an adverse effect of warfarin use

Answer 40

Bleeding

Question 41

Warfarin is contraindicated in ___ because ___

Answer 41

Pregnancy Crosses the placental barrier readily and causes haemorrhagic disease of the foetus. It also affects fetal proteins containing gamma-carboxyglutamate residues

Question 42

Name 4 thrombolytic agents

Answer 42

1. tPA (alteplase) 2. Urokinase 3. Streptokinase 4. Anistreplase

Question 43

MOA of thrombolytic agents

Answer 43

Plasminogen activators which increase the conversion of plasminogen to plasmin, and thus increases fibrinolysis of fibrin clots / mesh, thus dissolving blood clots

Question 44

State 3 clinical uses of thrombolytics

Answer 44

1. Emergency treatment in coronary artery thrombosis 2. Peripheral artery thrombosis and emboli 3. Ischaemic stroke

Question 45

Administering thrombolytics for ischaemic stroke must be done within (time window)

Answer 45

Less than 4.5 hours

Question 46

Can thrombolytics be used in haemorrhagic stroke?

Answer 46

No

Question 47

State 2 routes of administration for thrombolytics

Answer 47

1. Intracoronary 2. Intravenous

Question 48

State an adverse effect of thrombolytics

Answer 48

Bleeding

Question 49

Thrombolytics are contraindicated in 2 kinds of patients

Answer 49

1. Healing wounds 2. Pregnancy