6.2.2 Antiplatelet Drugs and Fibrinolytics

Question 1

What are 3 examples of ADP receptor antagonists?

Answer 1

Clopidogrel
Prasugrel
Ticagrelor

Question 2

How do ADP receptor antagonists work?

Clopidogrel Prasugrel Ticagrelor

Answer 2

Inhibit binding of ADP to P2Y12 receptor

Inhibits activation of GPIIb/IIIa receptors (independent of COX pathway)

Less aggregation

Question 3

What are the characteristics of each of the ADP receptor antagonists?

Answer 3

Clopidogrel
Slow onset of action without a loading dose
Irreversible inhibitor of P2Y12

Prasugrel
Fast onset of action
Irreversible inhibitor of P2Y12

Ticagrelor
Fast onset of action
Reversible inhibitor, different site to clopidogrel

All have active hepatic metabolites

Question 4

What are the adverse effects of ADP receptor antagonists?

Clopidogrel Prasugrel Ticagrelor

Answer 4

Bleeding
GI upset- dyspepsia and diarrhoea
Thrombocytopenia

Question 5

When should you not use ADP receptor antagonists?

Clopidogrel Prasugrel Ticagrelor

Answer 5

High bleed risk patients
Renal and/or hepatic impairment

Question 6

What are the important drug to drug interactions with ADP receptor antagonists?

Answer 6

Clopidogrel requries CYPs for activation

CYP inhibitors- omeprazole, ciprofloxacin, erythromycine, some SSRIs

Need to consider use of other PPIs with clopidogrel

Ticagrelor can interact with CYP inhibitors and inducers

Caution when co-prescribing with other antiplatelet and anti-coagulant agents or NSAIDs- increased bleeding risk

Question 7

How many days prior to surgery should you stop ADP receptor antagonists?

Clopidogrel Prasugrel Ticagrelor

Answer 7

Up to 7 days prior to surgery

Question 8

When are ADP receptor antagonists used?

Clopidogrel Prasugrel Ticagrelor

Answer 8

Ischaemic stroke
- Clopidogrel long-term monotherapy
- Where aspirin is contraindicated

N/STEMI- aspirin plus
- PCI plus prasugrel unless bleeding risk very high (ticagrelor or clopidogrel)
- No PCI ticagrelor unless bleeding risk very high (clopidogrel)

Question 9

How long should ADP receptor antagonists be used after N/STEMI?

Clopidogrel Prasugrel Ticagrelor

Answer 9

Usually up to 12 months

Question 10

What determines the use of ADP receptor antagonists?

Clopidogrel Prasugrel Ticagrelor

Answer 10

Age
Coronary anatomy
Bleed risk

Question 11

For ACS what is the best ADP receptor antagonist alongside aspirin?

Answer 11

Ticagrelor has faster onset of action

Question 12

What is an example of a phosphodiesterase inhibitor?

Answer 12

Dipyridamole

Question 13

How do phosphodisesterase inhibitors work?

Dipyridamole

Answer 13

Inhibits cellular reuptake of adenosine

Increased concentration of adenosine

Inhibits platelet aggregation via adenosine (A2) receptors

Also prevents cAMP degradation, leads to inhibited expression of GPIIb/IIIa

Question 14

What are the adverse effects of phosphodiesterase inhibitors?

Dipyridamole

Answer 14

Vomiting and diarrhoea
Dizziness

Question 15

What are the important drug to drug interactions with dipyridamole?

Answer 15

Antiplatelets and anticoagulants
Adenosine

Question 16

When is dipyridamole used?

Answer 16

Secondary prevention of ischaemic stroke and TIAs

Adjunct for prophylaxis of thromboembolism following valve replacement

Stroke- modified release

Question 17

What is an example of a Glycoprotein IIb/IIIa inhibitor?

Answer 17

Abciximab

Question 18

How do glycoprotein IIb/IIIa inhibitors work?

Abciximab

Answer 18

Blocks binding of fibrinogen and von Willebrand factor (vWF)

Targets final common pathway- more complete platelet aggregation

Question 19

How are Glycoprotein IIb/IIIa inhibitors administered?

Abciximab

Answer 19

IV

Question 20

What are the adverse drug effects of Glycoprotein IIb/IIIa inhibitors?

Abciximab

Answer 20

Bleeding

Dose adjustment needed for body weight

Question 21

What are the important drug to drug interactions of Glycoprotein IIb/IIIa inhibitors?

Abciximab

Answer 21

Caution with other antiplatelet and anticoagulant agents

Question 22

When are Glycoprotein IIb/IIIa inhibitors used?

Abciximab

Answer 22

Specialist use in high risk percutaneous transluminal coronary angioplast patients with other drugs (PCI- stents)

Question 23

Give two examples of fibrinolytic agents

Answer 23

Streptokinase
Alteplase

Question 24

What do Fibrinolytic agents do?

Streptokinase Alteplase

Answer 24

Dissolve the fibrin meshwork of a thrombus

Question 25

How do fibrinolytic agents work?

Streptokinase Alteplase

Answer 25

Converts plasminogen to plasmin which enables degradation of fibrin

Question 26

When are fibrinolytic agents used?

Streptokinase Alteplase

Answer 26

Acute ischaemic stroke < 4.5 hours from symptoms

Following STEMI acute vs primary PCI

Question 27

Why can streptokinase only be used once?

Answer 27

Antibodies develop against it

Question 28

What are the adverse effects of fibrinolytics?

Streptokinase Alteplase

Answer 28

Bleeding

Question 29

What are the important drug to drug interactions of fibrinolytics?

Streptokinase Alteplase

Answer 29

Antiplatelets and anticoagulants

Question 30

What is the use of tranexamic acid?

Answer 30

Heavy periods

Opposite effect to fibrinolytics

Inhibition of fibrinolysis

Question 31

Thrombolysis vs PCI following MI

Answer 31

PCI is preferred with acute STEMI if (some NSTEMI patients) :
- Presentation within 12 hours of onset symptoms
- PRimary PCI can be delivered within 120 minutes of time when fibrinolysis could have been given

Question 32

What is a negative consequence of PCI?

Answer 32

Reperfusion injury

Reactive oxygen species and Ca2+ to damaged tissue causing increased damage

Question 33

What is used in secondary prevention of ACS?

Answer 33

Once haemodynamically stable:
- ACEi (ARB is CI)
- Beta blockers
- Dual antiplatelet therapy ~75 mg aspirin + ADP receptor antagonist
- Statin

Plus cardiac rehabilitation e.g. exercise