Ticlopidine and clopidogrel

These are thienopyridine derivatives. They cause blockage of platelet aggregation.


Mechanism of action:
ADP gets bind to receptors on platelets resulting in activation of GP IIb/IIIa receptors, which is important for platelet binding to fibrinogen and to each other. Ticlopidine and clopidogrel cause interference in binding of ADP to receptors on platelets.

The inhibitory effect is irreversible and this effect remains as long as the platelet life.

Pharmacokinetics:
The drugs get strongly bind to plasma proteins after ingesting orally. Metabolism takes place extensively in the liver by cytochrome P450 system releasing active metabolites.

Maximum activity reached in 3-6 days. Its elimination takes place through kidney and feces.

Therapeutic uses:
These are effective in the prevention of cerebrovascular disease, cardiovascular disease and peripheral vascular disease.

These are used for insertion of stents in myocardial infarction.

Adverse effects:
It may cause prolonged bleeding. Thrombocytopenic purpura is also another adverse effect. Ticlopidine may also cause neutropenia.

Clopidogrel may also cause abdominal pain, chest pain and flulike symptoms.

Dosage:
Ticlopidine is taken orally in the 250 mg, tablet form BD with food.

The maintenance dose of clopidogrel is 75 mg per day.

Drug interactions:
Food causes interference in the absorption of ticlopidine but not of clopidogrel.

These drugs can stop activity of cytochrome P450 and that is why they may interfere with the metabolism of drugs such as tolbutamide, phenytoin, warfarin, and tamoxifen, if taken together.