Drugs Used In Coagulation Disorders I: Antiplatelet Agents

Question 1

What are the adverse effects of Aspirin?

Answer 1

Peptic ulcer

Bleeding

Question 2

Does aspirin have good or bad oral absorption?

Answer 2

Good

Question 3

How is aspirin administered?

Answer 3

Orally

Question 4

Does aspirin have high or low plasma protein binding?

Answer 4

High

Question 5

What does the 1st pass metabolism result in?

Answer 5

The formation of salicylic acid which is a reversible inhibitor

Question 6

What is the dose of Aspirin when used for platelet aggregation?

Answer 6

50-200mg

Question 7

What is the dose of aspirin when used for analgesic and antipyretic usages?

Answer 7

500mg

Question 8

What are the clinical indications of Aspirin?

Answer 8

Pain, fever, inflammation
Primary or secondary prophylaxis of arterial thromboembolic diseases
Acute cases - unstable angina, MI, coronary angioplasty, stroke

Question 9

What us dual anti platelet therapy?

Answer 9

ASA and P2Y12 receptor antagonist

Question 10

What is the mechanism of action of aspirin?

Answer 10

Irreversible inhibition of COX in PLT
Resulting in decreased TXA2 and PGI2 synthesis
No platelet activation

Question 11

What is the action of the COX enzyme?

Answer 11

Converts AA to TXA2

Question 12

What are the activators of platelets?

Answer 12

ADP
TXA2
Collagen
5-HT
Thrombin

Question 13

Name the thienopyridines

Answer 13

Ticlopidine 
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor

Question 14

What is the mechanism of action of thienopyridines?

Answer 14

They are P2Y12 receptor non-competitive antagonists at the ADP receptor on platelets - they Decrease platelet aggregation

Question 15

What are the clinical uses of the thienopyridines?

Answer 15

Cardio and cerebrovascular circulatory problems (TIA, stroke)
Dual anti platelet therapy: ASA +
P2Y12 receptor antagonist - decrease risk of
ACS and prevent coronary stent
thrombosis

Question 16

What are the adverse effects of thienopyridines?

Answer 16

GI problems
Minor bleeding
Rarely Leuko and thrombocytopenia (especially Ticlopidine)

Question 17

Which thienopyridines are most likely to cause thrombocytopenia and leukopenia?

Answer 17

Ticlopidine

Question 18

Where are the thienopyridines activated?

Answer 18

In the liver

Question 19

Are thienopyridines prodrugs?

Answer 19

Yes

Question 20

Do thienopyridines have good or bad absorption?

Answer 20

Good

Question 21

How are thienopyridines eliminated?

Answer 21

Renal and fecal elimination

Question 22

Do thienopyridines have low or high protein binding?

Answer 22

High

Question 23

What are the CYP2C19 inhibitors?

Answer 23

Omeprazol
Fluoxetine
Fluconazole

Question 24

What is Clopidogrel inhibited by?

Answer 24

CYP2C19

Question 25

What is the mechanism of action of Vorapaxar?

Answer 25

PAR-1 antagonist (antagonist of the thrombin receptor)

Question 26

What is the clinical use of Vorapaxar?

Answer 26

MI (secondary prophylaxis) | Peripheral artery thrombosis (combination with aspirin)

Question 27

Where is Vorapaxar metabolised?

Answer 27

The liver

Question 28

What enzyme metabolised Vorapazar?

Answer 28

CYP3A

Question 29

How is Vorapaxar administered?

Answer 29

Orally

Question 30

What are the contraindications of Vorapaxar?

Answer 30

Bleeding TIA Stroke

Question 31

What are the side effects of Vorapaxar?

Answer 31

Bleeding

Question 32

What are the side effects of Abciximab?

Answer 32

``` Bleeding Thrombocytopenia Hypotension Bradycardia Nausea Vomiting ```

Question 33

How is Abciximab administered?

Answer 33

IV

Question 34

What is the metabolic half life of Abciximab?

Answer 34

Short - 30mins

Question 35

What is the biological half life/duration of action of Abciximab?

Answer 35

18-24h

Question 36

What are the clinical indications of Abciximab?

Answer 36

PCI in coronary syndrome

Question 37

What is the mechanism of action of Abciximab?

Answer 37

GP IIb/IIIa receptor antagonist decreasing platelet aggregation Monoclonal antibody Irreversible antagonist

Question 38

What is the mechanism of action of Eptifibatide and Tirofiban?

Answer 38

GPIIb/IIIa receptor antagonist decreasing platelet aggregation Synthetic competitive inhibitor

Question 39

What is the clinical use of Eptifibatide?

Answer 39

PCI in coronary syndrome

Question 40

How are Eptifibatide and Tirofiban administered?

Answer 40

Continuous IV infusion due to their very short half life

Question 41

What is the duration of action of Eptifibatide and Tirofiban?

Answer 41

2-4 hours

Question 42

What is the mechanism of action of Dipyridamole and Cilostazol?

Answer 42

PDE inhibition (or adenosine uptake inhibition) leading to increased cAMP levels leading to activation of PKA - vasodilation - inhibition of platelet function

Question 43

How are Dipyridamole and Cilostazol administered?

Answer 43

IV

Question 44

What is the clinical indications of Dipyridamole and Cilostazol?

Answer 44

In combination with Warfarin as primary prophylaxis of thromboembolism in patients with prosthetic valves

Question 45

What is the adverse effects of Dipyridamole and Cilostazol?

Answer 45

High does can lead to risk of coronary steal effect

Question 46

When are anti-platelet drugs effective?

Answer 46

Only in arterial thrombosis

Question 47

How do we measure PLT function?

Answer 47

Using bleeding time (not very accurate)

Question 48

What does endothelial damage result in?

Answer 48

The exposure of sub-endothelial collagen and vWF

Question 49

Where is Gp1b receptor located?

Answer 49

Platelet

Question 50

What does Gp1b receptor on platelets bind to?

Answer 50

VWF

Question 51

What is the result of Gp1b adherence to vWF?

Answer 51

Platelet activation

Question 52

What are released from platelet granules?

Answer 52

ADP, 5HT, TXA2

Question 53

What does ADP bind to?

Answer 53

P2Y12 receptors resulting in platelet aggregation

Question 54

What is the result of 5HT?

Answer 54

Locally as a platelet aggregator and vasoconstrictor

Question 55

What is the result of TXA2?

Answer 55

It causes platelets to change shape, causing activation and aggregation

Question 56

Is COX2 always activated?

Answer 56

No, it is preferentially activated and expressed at sights of inflammation

Question 57

What is the result of TXA2?

Answer 57

Vasoconstriction

Question 58

What is the action of aspirin?

Answer 58

Irreversible covalent acetylation of cox Irreversible inhibition of platelet production of TXA2 the entire life of the platelet

Question 59

How should aspirin be administered in acute MI?

Answer 59

Aspirin should be chewed or crushed so that you achieve high blood concentrations quickly

Question 60

What is the mechanism of action of thienopyridines?

Answer 60

Irreversibly blocking the ADP receptor (P2Y12) on platelets

Question 61

What is a pseudo allergy?

Answer 61

Symptoms of allergies which are not IgE mediated

Question 62

Which anti-platelet drug results in pseudo allergy?

Answer 62

Aspirin

Question 63

When is pseudo allergy more likely?

Answer 63

In patients with a history of allergies

Question 64

What is the cause of he aspirin induced pseudo Allergy?

Answer 64

Block of cox leading to increased leukotrienes

Question 65

When do we use dual anti platelet therapy

Answer 65

1. To reduce the risk of ACS and prevent coronary stent thrombosis 2. To reduce the long term risk of cardiovascular events in patients with peripheral artery disease 3. Acute ST elevation MI to prevent coronary artery thrombosis 4. Prevention of Ischemic stroke in patients with atherosclerosis and known cerebrovascular disease

Question 66

What is a side effect of ticlopidine?

Answer 66

Neutropenia and granuloytopenia

Question 67

What should you do before putting a patient on ticlopidine and after the initiation of therapy?

Answer 67

CBC

Question 68

What does GpIIb/IIIa bind to?

Answer 68

Fibrinogen

Question 69

What is the result of GPIIb/IIIa and fibrinogen binding?

Answer 69

Activation and cross linking of platelets leading to the formation of the platelet plug

Question 70

What type of antibody is Abciximab?

Answer 70

Monoclonal IgG

Question 71

What is a major SE of GPIIb/IIIa inhibitors?

Answer 71

Drug induced thrombocytopenia

Question 72

What should be monitored frequently in platelets using GPIIb/IIIa inhibitors?

Answer 72

Platelet count

Question 73

What I the effect of anti platelet drugs on bleeding time

Answer 73

Prolonged bleeding time

Question 74

What is the clinical significance of bleeding time?

Answer 74

Patients on anti platelet drugs | vWF disease

Question 75

What does bleeding time measure?

Answer 75

Platelet function

Question 76

What can be used as symtomatic tx of intermittent claudication?

Answer 76

Cilostazol due to its vasodilatory effects

Question 77

Is there an antidote for Thienopyridines?

Answer 77

No

Question 78

What is P2Y12?

Answer 78

It is a chemoreceptor for ADP Gi coupled Involved in platelet aggregation

Question 79

What is PAR1?

Answer 79

Protease activated receptor

Question 80

How is PAR1 activated?

Answer 80

Via serine proteases such as thrombin

Question 81

Which coagulation factors are vitamin K dependent?

Answer 81

Factors II, VII, IX, X, proteins C and S.

Question 82

What are the endogenous platelet activators?

Answer 82

``` TxA2 ADP Collagen 5HT Thrombin ```

Question 83

Name the type of anti platelet drugs?

Answer 83

``` COX inhibitors P2Y12 Receptor antagonists-Thienopyridines GPIIb/IIIa receptor antagonists PDE inhibitors PAR-1 antagonists ```

Question 84

Name the GPIIb/IIIa receptor antagonists

Answer 84

Abciximab Eptifibatide Tirofiban

Question 85

Name the P2Y12 receptor antagonists

Answer 85

``` Ticlopidine Clopidogrel Prasugrel Cangreler Ticagrelor ```

Question 86

Name the PAR1 antagonist

Answer 86

Vorapaxar

Question 87

Name the PDE inhibitors

Answer 87

Dipyridamole | Cilostazole