Antiplatelets

Question 1

Name 3 commonly used antiplatelet drugs and state their classes.

Answer 1

1) Aspirin - NSAID
2) Clopidogrel - ADP receptor antagonist
3) Ticagrelor - ADP receptor antagonist

Question 2

Give the 4 common clinical indications for the use of clopidogrel and state why it is used.

Answer 2

1) ACS - rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent risk of mortality.
2) To prevent occlusion of coronary artery stents.
3) Long term secondary prevention of thrombotic arterial events in patients with Cardiovascular, cerebrovascular and peripheral artery disease.
4) AF - reduce risk of intracardiac thrombus and embolic stroke. Used when Warfarin and NOACs are contraindicated.

Question 3

1) What drug is clopidogrel generally prescribed with?
2) What is the basic MoA of clopidogrel?
3) Why is the action of clopidogrel synergistic with the action of aspirin?

Answer 3

1) Usually prescribed with Aspirin, although can be used alone if aspirin is contraindicated or not tolerated.
2) Prevents platelet aggregation and reduces risk of arterial occlusion by binding irreversibly to ADP receptors (P2Y12 subtype) on platelet surfaces.
3) Because the action of clopidogrel is independent of the COX pathway.

Question 4

Give 3 important adverse effects of clopidogrel.

Answer 4

1) Bleeding - can be serious, particularly if of GI or intracranial nature or if following a surgical procedure.
2) GI upset - dyspepsia, abdominal pain, diarrhoea.
3) Thrombocytopenia - rare.

Question 5

1) State one contraindication for clopidogrel.
2) What must you do if a person prescribed clopidogrel requires elective surgery?
3) Give one caution for the use of clopidogrel.

Answer 5

1) Should not be prescribed for patients with active bleeding.
2) Clopidogrel may need to be stopped 7 days prior to elective surgery and other procedures.
3) Should be used with caution in patients with renal and hepatic impairment. Especially if there is an increased risk of bleeding.

Question 6

1) What does clopidogrel require in order to have an active antiplatelet effect?
2) Describe how the efficacy of clopidogrel might be decreased.
3) Name 5 drugs/ drug classes that could potentially reduce the efficacy of clopidogrel.

Answer 6

1) Pro-drug and requires metabolism by hepatic CYP450 enzymes to become active.
2) Efficacy can be reduced by CYP450 inhibitors that inhibit clopidogrel activation.
3) Omeprazole, ciprofloxacin, erythromycin, some antifungals and some SSRIs.

Question 7

1) What are the drugs of choice to provide gastroprotection for patients taking clopidogrel and why is this?
2) Co-prescription of what with clopidogrel can increase the risk of bleeding?

Answer 7

1) Where gastroprotection with a PPI is required for patients taking clopidogrel, lansoprazole or pantoprazole are preferred over omeprazole as they are less likely to inhibit clopidogrel activation.
2) Antiplatelets, anticoagulants or NSAIDs.

Question 8

1) How is clopidogrel available for administration?
2) How long do low doses of clopidogrel require to reach their full antiplatelet effect?
3) How should you prescribe clopidogrel when a rapid effect is needed? For example, in ACS.

Answer 8

1) Orally.
2) Low doses require up to a week to reach their full antiplatelet effect.
3) For a rapid effect: prescribe loading dose (300mg PO for ACS) in the once only section, and then commence a regular maintenance dose of 75mg OD.

Question 9

After insertion of a drug eluting coronary stent, how long should dual antiplatelet therapy be continued for and why is this?

Answer 9

Dual antiplatelet therapy should be continued for 12 months to reduced risk of stent thrombosis. It should not be discontinued prematurely without prior discussion with a cardiologist.

Question 10

1) What is a consequence of the fact that clopidogrel binds irreversibly?
2) When should clopidogrel NOT be stopped prior to elective surgery?
3) What might be required if a patient has active bleeding in an emergency situation when they are taking clopidogrel?

Answer 10

1) This means that it takes the lifespan of the platelet (7-10 days) for the effects of clopidogrel to wear off.
2) If the risk of stopping clopidogrel exceeds the risk of continuing. Therefore, in patients who are taking clopidogrel for 12 months after coronary artery stent insertion, surgery should be delayed if possible.
3) in emergency cases, patients taking clopidogrel may require a platelet infusion to help stop bleeding.

Question 11

1) When is ticagrelor indicated for use?
2) What is the basic MoA of Ticagrelor?
3) Why might Ticagrelor be of use in patients who are poor metabolisers?

Answer 11

1) Prevention of thrombotic events such as stroke or MI in patients with ACS or MI with ST elevation (secondary prevention). Prevention of atherothrombotic events post PCI.
2) Reversible allosteric antagonist of P2Y12 receptors.
3) Because it is not a prodrug and so does not need to be metabolised.

Question 12

1) Give 2 contraindications for the use of Ticagrelor.
2) What is the recommendation for monitoring patients taking Ticagrelor?
3) In what type of patient should caution be used if prescribing Ticagrelor?
4) In what type of patients should Ticagrelor be avoided due to evidence of toxicity in animal studies?

Answer 12

1) Active bleeding and history of intracranial haemorrhage.
2) Monitor renal function 1 month after initiation in patients with ACS.
3) Those with Hepatic impairment.
4) Those who are pregnant or breastfeeding.

Question 13

Give the 4 common clinical indications for the use of Aspirin and state why aspirin is used.

Answer 13

1) ACS and acute ischaemic stroke - rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality.
2) Long term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular or peripheral artery disease.
3) AF - to reduce the risk of intracardiac thrombus or embolic stroke where Warfarin and NOACs are contraindicated.
4) Control of mild to moderate pain or fever, although other drugs are usually preferred.

Question 14

1) Describe the mechanism of action of aspirin.

2) When does the antiplatelet effect of aspirin occur and how long does it last?

Answer 14

1) Irreversibly inhibits COX to reduce production of pro-aggregation factor Thromboxane from arachidonic acid. This reduces platelet aggregation and risk of arterial occlusion.
2) Occurs at low doses and lasts for the lifetime of a platelet, as the platelet will not have a nucleus to synthesise new COX.

Question 15

1) What is the most common adverse effect of Aspirin?
2) Name 3 more serious adverse effects of Aspirin.
3) What can aspirin cause in regular high dose therapy?
4) Describe the pathway for how aspirin can become life threatening in overdose.

Answer 15

1) GI irritation.
2) GI ulceration, GI haemorrhage, hypersensitivity reactions including bronchospasm.
3) Tinnitus.
4) Hyperventilation and hearing changes > metabolic acidosis and confusion > convulsions > cardiovascular collapse > respiratory arrest.

Question 16

1) Why should Aspirin not be given to children aged under 16 years?
2) Apart from children, who else should not take Aspirin?
3) What condition is aspirin not routinely contraindicated in?

Answer 16

1) Due to the risk of Reye’s syndrome, a rare but life threatening illness that affects the liver and brain.
2) People with aspirin hypersensitivity (those who have had bronchospasm or other allergic symptoms triggered by aspirin or other NSAIDs).
3) Not routinely contraindicated in asthma.

Question 17

1) Why should Aspirin be avoided in the third trimester of pregnancy?
2) Give 2 types of patient where aspirin should be used with caution.

Answer 17

1) Because prostaglandin inhibition may lead to premature closure of the ductus arteriosus.
2) Used with caution in those with peptic ulceration (prescribe gastroprotection) and those with gout (may trigger acute attack).

Question 18

Why should caution be taken when prescribing aspirin as part of dual antiplatelet therapy or with an anticoagulant?

Answer 18

Because although therapeutically beneficial, the combination can lead to an increased risk of bleeding.

Question 19

1) How is aspirin available for administration?
2) In ACS, how should Aspirin be prescribed?
3) For Acute ischaemic stroke, how should Aspirin be prescribed?
4) How should aspirin be prescribed for long term prevention of thrombosis?
5) How should Aspirin be prescribed for pain?

Answer 19

1) Orally or rectally (for higher doses).
2) Once only loading dose of 300mg, followed by a regular maintenance dose of 75mg OD.
3) 300mg OD for 2/52, before switching to a maintenance dose of 75mg daily.
4) low dose 75mg daily.
5) Higher doses are required for pain management, can prescribe up to 4g daily, taken in divided doses.

Question 20

1) Prescription of what other drug should be considered for patients taking low dose aspirin?
2) What is the usual dose that is used for the additional drug?
3) List 4 risk factors that put patients at increased risk of GI complications when taking aspirin.

Answer 20

1) Gastroprotection, especially for those at increased risk of GI complications.
2) Omeprazole 20mg PO OD.
3) >65, previous peptic ulcer disease, comorbidities such as CVD or diabetes, concurrent therapy with other drugs with GI side effects (NSAIDs and prednisolone).

Question 21

1) In order to minimise gastric irritation, when should Aspirin be taken?
2) What is the most appropriate form of monitoring for patients taking aspirin?
3) Why is aspirin not recommended as primary prevention for vascular events in the UK?

Answer 21

1) Aspirin should be taken after food.
2) Enquiry about side effects is the most appropriate.
3) RCTs and meta analyses have found that any potential benefits of low dose aspirin for primary prevention are offset by the increased risk of serious bleeding.

Question 22

1) What class of drug is dipyridamole?
2) State the 2 main clinical indications for the use of Dipyridamole.
3) When is dipyridamole used as first line therapy and when is it used as second line therapy?

Answer 22

1) Phosphodiesterase inhibitor
2) Cerebrovascular disease for secondary prevention of a stroke and to induce tachycardia during a myocardial perfusion scan in the diagnosis of ischaemic heart disease.

3) First line therapy: following a TIA.
Second line therapy: following an ischaemic stroke where clopidogrel is contraindicated or is not tolerated.

Question 23

1) What are the 2 types of effect that Dipyridamole has?
2) The MoA of dipyridamole is controversial, but what is the end effect of the drug?
3) How does dipyridamole cause vasodilation?

Answer 23

1) Antiplatelet and vasodilator effects.
2) Increase in intra-platelet cAMP > inhibition of platelet aggregation > reduces risk of arterial occlusion.
3) Blocks cellular uptake of adenosine, prolonging it’s effect on blood vessels to produce vasodilation.

Question 24

1) State 4 side effects of Dipyridamole.
2) Name 3 types of patients that dipyridamole should be used with caution in.
3) What does reduced perfusion after dipyridamole indicate?

Answer 24

1) Headache, flushing, dizziness, GI symptoms, increased risk of bleeding, thrombocytopenia.
2) Ischaemic heart disease, aortic stenosis, heart failure (causes vasodilation and tachycardia that can exacerbate these conditions).
3) Reduced perfusion after dipyridamole indicates cardiac ischaemia.

Question 25

1) Why does use of Dipyridamole increase risk of cardiac arrest in patients being prescribed adenosine?
2) When is there a further increased risk of bleeding when dipyridamole is used?

Answer 25

1) it inhibits cellular uptake of adenosine, which prolongs the effects of adenosine on the heart, increasing the risk of cardiac arrest. Therefore, the dose of adenosine should be reduced in patients treated with dipyridamole.
2) If it is combined with other antiplatelets or anticoagulants.

Question 26

1) For therapeutic purposes, how is dipyridamole usually administered?
2) For secondary prevention of stroke, how should you prescribe dipyridamole?
3) What are the only two reasons that dipyridamole should be stopped?

Answer 26

1) Orally.
2) Dipyridamole modified release, 200mg BD.
3) If adverse effects are intolerable or new contraindications develop (as dipyridamole is a long term treatment).

Question 27

1) What class of drug is Tirofiban?
2) When might the use of Tirofiban be indicated?
3) Describe the basic mechanism of action of Tirofiban.
4) Are the effects of Tirofiban reversible?

Answer 27

1) Glycoprotein IIb/IIIa receptor antagonist.
2) Prevention of atherothrombotic events post PCI.
3) Reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor. This is the major platelet surface receptor involved in platelet aggregation.
4) Yes, they are reversible following the cessation of the infusion of Tirofiban.

Question 28

1) Name the 3 antiplatelets that can be used for secondary prevention of cardiovascular events.
2) Name the 4 antiplatelets that can be used for prevention of atherothrombotic events post PCI.

Answer 28

1) Aspirin, Dipyridamole, Clopidogrel/Ticagrelor

2) Aspirin, Dipyridamole, Clopidogrel/Ticagrelor, Tirofiban