TeacherOfMedicine: Antiplatelet drugs, ADP-receptor antagonists

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.

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.

The most common adverse effect of clopidogrel is bleeding, which can be serious, particularly if gastrointestinal, intracranial or following a surgical procedure.
Gastrointestinal upset, including dyspepsia, abdominal pain and diarrhoea, is also common.
As with other antiplatelet agents, clopidogrel can rarely affect platelet numbers as well as function, causing thrombocytopenia.

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.

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.

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