CV: Antiplatelet drugs

Question 1

Why are antiplatelet drugs successful in preventing thrombus formation in the arterial circulation?

Answer 1

In the faster flowing vessels, thrombi are composed mainly of platelets with little fibrin (opposite in slower moving venus)

Question 2

Aspirin is used in what? primary or secondary prevention?

Answer 2

The use of aspirin in primary prevention of cardiovascular events, in patients with or without diabetes, is of unproven benefit.

Long-term use of aspirin is of benefit in established cardiovascular disease (secondary prevention); unduly high blood pressure must be controlled before aspirin is given.

If high risk of GI bleeding, PPI can be used.

Question 3

Before the initiation of aspirin for secondary prevention, uncontrolled what needs to be treated?

Answer 3

hypertension

Question 4

What is the mechanism of action of aspirin?

Answer 4

Aspirin inhibits platelet cycloxygenase, a key enzyme in thromboxane A2 (TXA2) generation.

Thromboxane A2 triggers reactions that lead to platelet activation and aggregation, aspirin acts as a potent antiplatelet agent by inhibiting generation of this mediator.

Question 5

Clopidogrel is licensed for the prevention of atherothrombotic events in patients with a history of symptomatic ischaemic disease.

Clopidogrel, in combination with low-dose what?, is also licensed for ACS without ST-segment elevation.

How long is this combination given for?

Answer 5

Clopidogrel is licensed for the prevention of atherothrombotic events in patients with a history of symptomatic ischaemic disease. Clopidogrel, in combination with low-dose aspirin, is also licensed for acute coronary syndrome without ST-segment elevation; in these circumstances the combination is given for up to 12 months (most benefit occurs during the first 3 months; there is no evidence of benefit beyond 12 months).

Question 6

Clopidogrel, in combination with low-dose aspirin, is also licensed for acute myocardial infarction WITH ST-segment elevation. How does the length of treatment for STEMI differ to NSTEMI?

Answer 6

Clopidogrel, in combination with low-dose aspirin, is also licensed for acute myocardial infarction with ST-segment elevation; the combination is licensed for at least 4 weeks, but the optimum treatment duration has not been established.

Question 7

When would clopidogrel, combination with low-dose aspirin, be used for the prevention of atherothrombotic and thromboemobolic events in patients with AF (and at least one risk factor for a vascular event)?

Answer 7

When warfarin sodium is unsuitable.

Question 8

How does clopidogrel work?

Answer 8

The active metabolite of clopidogeel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

This action is irrerversible.

Question 9

What is dipyridamole used by mouth as an adjunct to?

Answer 9

Dipyridamoleis used by mouth as an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves. Modified-release preparations are licensed for secondary prevention of ischaemic stroke and transient ischaemic attacks.

Question 10

Modified-release preparations of dipyridamole are licensed for what? (2)

Answer 10

Dipyridamoleis used by mouth as an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves. Modified-release preparations are licensed for secondary prevention of ischaemic stroke and transient ischaemic attacks.

Question 11

How does dipyridamole work?

Answer 11

Dipyridamole inhibits the phosphodiesterase enzymes that normally break down cAMP (increasing cAMP levels and blocking the platelet aggregation response to ADP) and/or cGMP.

(Also interacts with adenosine: inhibits the cellular reuptake of adenosine into platelets, red blood cells, and endothelial cells leading to increased extracellular concentrations of adenosine)

Question 12

Prasugel, in combination with aspirin, is licensed for the prevention of atherothrombotic events in patients with acute coronary syndrome undergoing PCI; how long is the combination given for?

Answer 12

up to 12 months

Question 13

Irreversible inhibitor of the binding of ADP to P2Y12 receptor

Answer 13

Clopidogrel

Question 14

How does Prasugel work?

Answer 14

The same way to Clop, its active metabolite prevents the binding of ADP to its platelet receptor.

Question 15

Ticagrelor, in combination with aspirin, is licensed for what?

Answer 15

The prevention of atherothrombotic events in patients with ACS; the combination is usually given for up to 12 months.

Question 16

How does Ticagrelor work?

Answer 16

REVERSIBLE inhibitor of P2Y12ADP receptor on platelets.

Question 17

Phosphodiesterase inhibitor that leads to increased cellular cAMP levels and blocked platelet aggregation response to ADP

Answer 17

Dipyridamole inhibits the phosphodiesterase enzymes that normally break down cAMP (increasing cAMP levels and blocking the platelet aggregation response to ADP) and/or cGMP.

(Also interacts with adenosine: inhibits the cellular reuptake of adenosine into platelets, red blood cells, and endothelial cells leading to increased extracellular concentrations of adenosine)

Question 18

With regards to coronary stents, in what circumstances is clopidogrel given for 12 months vs 1 month following placement?

Answer 18

. Clopidogrel is recommended for 1 month following elective percutaneous coronary intervention with placement of a bare-metal stent, and for 12 months if percutaneous coronary intervention with placement of a bare-metal stent was for an acute coronary syndrome; clopidogrel should be given for 12 months following placement of a drug-eluting stent.

Question 19

Glycoprotein IIb/IIIa inhibitors work how?

Answer 19

They prevent platelet aggregation by blocking the binding of fibrinogen to receptors on platelets.

Question 20

Abcimiximab is a monoclonal antibody which binds to glycoprotein IIb/IIIa receptors and to other related sites; it is licensed as an adjunct to what in what circumstances?

Answer 20

Abciximab is a monoclonal antibody which binds to glycoprotein IIb/IIIa receptors and to other related sites; it is licensed as an adjunct to heparin (unfractionated) and aspirin for the prevention of ischaemic complications in high-risk patients undergoing percutaneous transluminal coronary intervention.

Question 21

How often should the monoclonal antibody abcimiximab be used? Why?

Answer 21

Abcimiximab should be used once daily (to avoid the additional risk of thrombocytopenia).

Question 22

Eptifibatide (in combination with heparin and aspirin) inhibits glycoprotein IIb/IIIa receptors and is licensed in what?

Answer 22

Eptifibatide is licensed for use to prevent early myocardial infarction in patients with unstable angina OR non-ST-segment-elevation MI.

Question 23

Tirofiban is another glycoprotein IIb/IIIa inhibitor which is licensed both for the prevention of early MI in patients with UA or NSTEMI and for the reduction of major CV events in patients with STEMI intended for PCI. What must it be used in combination with?

Answer 23

Tirofiban is always used with aspirin, clopidogrel and unfract heparin.

Question 24

When is epoprostenol used?

Answer 24

It is used to inhibit platelet aggregation during renal dialysis when heparins are unsuitable or contra-indicated.

Question 25

How does epoprostenol work?

Answer 25

Epoprostenol (prostacyclin) is a member of the eicosanoid family of lipid molecules.

It causes decreased Thromboxane-A2 and PDGF.

Also see iloprost a synthetic prostacylin analogue used as a vasodilator in severe raynauds phenomenon or ischiemia of limb; pulmonary hypertension and primary pulmonary hypertension.

Question 26

Phosphodiesterase inhibitor

Answer 26

Dipyridamole PDE5

Question 27

ADP receptor antagonists (3)

Answer 27

Clopidogrel
Prasugrel
Ticagrelor - reversible

Question 28

COX inhibitor

Answer 28

Aspirin irrerversibly inhibits COX-1, thereby blocking the formation of thromboxane A2

Question 29

Glycoprotein IIb/IIIa receptor antagonists (3)

Answer 29

Abciximab - irrerversible
Tirofiban - reversibly
Eptifibatide

Question 30

What type of drug is Cilostazol?

Answer 30

PDE3 inhibitor.
It is used to treat intermittent claudication. (See peripheral vascular disease deck).

Similar drug to dipyridamole.

Question 31

Glycoprotein IIb/IIIa receptor antagonists are most commonly used when?

Answer 31

Deployed during the surgical procedure (PCI) where stents are placed into narrowed vessels. They work by antagonising these receptors on the surface of platelets, with abciximab binding irrerversibly and tirofiban binding reversibly.

Question 32

What side effects can abciximab cause?

Answer 32

Bleeding
Thrombocytopenia
Nausea 
Vomiting
HYPOTENSION
Headache

Question 33

Which of the following is NOT a prodrug?

Clopidogrel
Prasugel
Ticagrelor

Answer 33

Ticagrelor is not a pro drug.