Aspirin and clopidogrel

Question 1

Explain the MoA of Aspirin

Answer 1

Aspirin irreversibly inhibits COX to reduce production of the pro-aggregatory factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion. The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of a platelet

Question 2

1) Outline the common and serious side effects caused by aspirin
2) What side effect can regular high-dose therapy with aspirin cause ?

Answer 2

1) GI irritation, haemorrhage
↳More serious: Peptic ulceration and hypersensitivity reactions including bronchospasm.
2) In regular high-dose therapy aspirin causes tinnitus.

Question 3

Aspirin is life-threatening in overdose. what are the features of an aspirin overdose?

Answer 3

1) Hyperventilation
2) Hearing changes (tinnitus, deafness)
3) Vasodialation and sweating
4) convulsions and rarely coma in severe overdose

Question 4

Which patients should aspirin be avoided in? (5)

Answer 4

1) children aged under 16 due to the risk of Reye’s syndrome
2) Aspirin/NSAID hypersensitivity (had bronchospasm or other allergic symptoms triggered by these drugs)
3) Third trimester of pregnancy
4) caution in peptic ulceration ( prescribe PPI)
5) Gout- may trigger attack

Question 5

what is Reye’s syndrome

Answer 5

a rare but life-threatening illness that principally affects the liver and brain

Question 6

Explain why aspirin should be used with caution in the third trimester of pregnancy (3)

Answer 6

1) Prostaglandin inhibition may lead to premature closure of the ductus arteriosus
2) Risk of hemorrhage
3) Increased duration of labor and therefore blood loss

Question 7

Can aspirin be used in breast feeding?

Answer 7

Avoid- possible risk of Reye’s syndrome; regular use of high doses could impair platelet function and produce hypoprothrombinaemia in infant if neonatal vitamin K stores low

Question 8

Outline the important interactions with regards to aspirin

Answer 8

Aspirin acts synergistically with other antiplatelet agents, can lead to increased risk of bleeding. Caution when given with other antiplatelet drugs (e.g. clopidogrel) and anticoagulants (e.g. heparin, warfarin)

Question 9

what is the dose and duration of aspirin indicated for an acute ischaemic stroke?

Answer 9

300 mg once daily for 14 days

Question 10

1) What is the dose of aspirin used for the management of pain
2) what is the maximum daily dose of aspirin?

Answer 10

300- 900 mg every 4–6 hours as required; maximum 4 g per day

Question 11

Gastroprotection should be considered for patients taking low-dose aspirin. Which patients are at increased risk of gastrointestinal complications and should be considered for treatment with a PPI? (4)

Answer 11

1) Age >65 years
2) Previous peptic ulcer disease
3) co-morbidities (such as cv disease, diabetes)
4) Concurrent therapy with other drugs with GI side effects, e.g. NSAIDs and prednisolone

Question 12

what is the maximum quantity of aspirin that can be sold OTC?

Answer 12

pharmacists can sell multiple packs up to a total quantity of 100 capsules or tablets in justifiable circumstances.

Question 13

What are ADP-receptor antagonists such as clopidogrel, ticagrelor, prasugrel indicated for? (3)

Answer 13

1) Treatment of ACS usually in combination with aspirin
2) To prevent occlusion of coronary artery stents, usually in combination with aspirin.
3) long-term secondary prevention alone or in combination with aspirin.

Question 14

Outline the MoA of ADP-receptor antagonists

Answer 14

1) prevent platelet aggregation and reduce the risk of arterial occlusion by binding irreversibly to ADP receptors on the surface of platelets.
2) As this process is independent of the COX pathway, its actions are synergistic with those of aspirin.

Question 15

What are the most common side effects of ADP-receptor antagonists? (4)

Answer 15

1) Bleeding
2) GI upset: dyspepsia, abdominal pain and diarrhoea
3) Skin reactions
4) Rarely: Thrombocytopenia

Question 16

who should ADP-receptor antagonists be used in caution with?

Answer 16

1) Avoid in active bleeding and may need to be stopped 7 days before elective surgery and other procedures
2) Caution in renal and hepatic impairment

Question 17

Clopidogrel is a pro-drug that requires metabolism by which enzyme to make it active?

Answer 17

Hepatic cytochrome P450 (CYP)

Question 18

outline the important interactions with regards clopidogrel, prasugrel and ticagrelor

Answer 18

1) Clopidogrel efficacy may be reduced by CYP inhibitors by inhibiting its activation. e.g. omeprazole, ciprofloxacin, erythromycin, some antifungals and some SSRIs
2) Prasugrel is also a pro-drug but is less susceptible to interactions.
3) Ticagrelor is not a pro-drug, but interacts with CYP inhibitors and inducers
4) caution when taken with other antiplatelet drugs

Question 19

When gastroprotection with a PPI is required for patients taking clopidogrel what options can be considered?

Answer 19

lansoprazole or pantoprazole are preferred over omeprazole as they are considered less likely to inhibit clopidogrel activation

Question 20

1) How long does it take for clopidogrel to reach its full antiplatelet effect?
2) When rapid effect is needed, what dose of clopidogrel can be given?

Answer 20

1) up to a week to reach their full anti-platelet effect

2) loading dose, normally 300 mg orally for ACS, before commencing 75mg maintenance dose