Thrombolytics

Question 1

Example of a Thrombolytic

Answer 1

Clopidogrel

Question 2

How do Thrombolytics work?

Answer 2

Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes the circulation. Clopidogrel prevents platelet aggregation and reduces the risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptors (P2Y12 subtype) on the surface of platelets. As this process is independent of the cyclooxygenase pathway, its actions are synergistic with those of aspirin.

Question 3

Indications of Thrombolytics

Answer 3

Clopidogrel is generally prescribed with aspirin, although clopidogrel may be used alone where aspirin is contraindicated or not tolerated.

For treatment of acute coronary syndrome (ACS), where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality.

To prevent occlusion of coronary artery stents.

For long-term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease.

To reduce the risk of intracardiac thrombus and embolic stroke in atrial fibrillation where warfarin and novel oral anticoagulants are contraindicated.

Question 4

Contraindications of Thrombolytics

Answer 4

Clopidogrel should not be prescribed for people with significant active bleeding and may need to be stopped 7 days before elective surgery and other procedures.

It should be used with caution in patients with renal and hepatic impairment, especially where patients otherwise have an increased risk of bleeding.

Question 5

Side effects of Thrombolytics

Answer 5

Common: Bleeding (which can be serious, particularly if gastrointestinal, intracranial or following a surgical procedure), gastrointestinal upset, including dyspepsia, abdominal pain and diarrhoea.

Rare: Thrombocytopenia.

Question 6

Interactions of Thrombolytics

Answer 6

Clopidogrel is a pro-drug that requires metabolism by hepatic cytochrome P450 enzymes to its active form to have antiplatelet effect. Its efficacy may be reduced by cytochrome P450 inhibitors by inhibiting its activation. Relevant examples include omeprazole, ciprofloxacin, erythromycin, some antifungals and some SSRIs. Where gastroprotection with a proton pump inhibitor (see Aspirin) is required for patients taking clopidogrel, lansoprazole or pantoprazole are preferred over omeprazole as they are considered less likely to inhibit clopidogrel activation. Co-prescription of clopidogrel with other antiplatelet drugs (e.g. aspirin), anticoagulants (e.g. heparin) or NSAIDs increases the risk of bleeding.

Question 7

Elimination of Thrombolytics

Answer 7

Renal (Urine) and Rectal (Faeces)

Question 8

Patient information on Thrombolytics

Answer 8

Clopidogrel is only available as an oral preparation. Low doses of clopidogrel require up to a week to reach their full antiplatelet effect

Clopidogrel can be given with or without food.

Advise patients that the purpose of treatment is to reduce the risk of heart attacks or strokes and to prolong life.

In those who are taking clopidogrel following the insertion of a drug-eluting stent, emphasise the importance of continuing treatment as directed, usually for 12 months, to make sure that the stent stays open and does not block and cause a heart attack.

Explain that if bleeding does occur while on treatment it might take longer than usual to stop. Patients should report any unusual or sustained bleeding to their doctor.