platelet aggregation inhibition

Thromboxane A2 (TXA2) produced by activated platelets stimulates activation of new platelets and increases platelet aggregation by mediating expression of GP IIb/IIIa in the cell membrane of platelets.

Circulating fibrinogen binds to GP IIb/IIIa receptors causing aggregation.

Thrombin converts fibrinogen to fibrin which is cross linked by factor XIII to form a clot.

Aspirin inhibits prostaglandin formation which leads to TXA2 inhibition.

Clopidrogel which is a prodrug activated by CYP2C19 irreversitly inhibits P2Y12 and ADP receptors which blocks the activation of GP IIb/IIIa receptors to bind with fibrinogen.

cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.

vitamin K cycle

The vitamin K cycle is essential for post-translational gamma-carboxylation of several blood coagulation factors and, therefore, coagulation. (VKORC1: vitamin K epoxide reductase complex 1, CYP2C9: cytochrome P450, family 2, subfamily C, polypeptide 9)

Cardiovascular pharmacogenomics and individualized drug therapy

Nature Reviews Cardiology 2009

ischemic preconditioning

 

 

Top, Territorial MCA infarction in a patient without prodromal TIA. Bottom, Territorial MCA infarction in a patient with prodromal TIA ≤4 weeks. From left to right, MTT <12 hours, CBF <12 hours, ADC <12 hours, final T2 (3 to 7 days).

TIAs may have an endogenous neuroprotection in the human brain due to ischemic preconditioning. 

Transient Ischemic Attacks Before Ischemic Stroke: Preconditioning the Human Brain?

Stroke 2004