Antiplatelet agents, plaque, misc for stroke

1. Mechanism of injury is plaque rupture that causes platelet activation, exposure of platelets to VWF that tethers and causes to adhere other platelets to site. Platelet granules release alpah granules and fibrinogen and ADP that causes more platelet activation. Platelet also derives thromboxane A2 and thrombin. Also get G2 protein receptor, platelet shape change (round to discoid with extending filaments) increased cAMP intracellularly, P2Y1 receptor causes an ADP mediated increased cytosolic calcium, P2Y12 receptor potentiates granule secretion, recruitment of platelets and aggregation.
2. ASA blocks thromboxane A 2 mediated path. Plavix blocks P2Y12 receptor. Dipyridamole increases ic cAMP deterring platelet activation and is vasodilatory due to secondary inhibition of phosphodiesterase (PDE). It blocks ADP nucleic acid uptake in dose dependent manner.
3. Acetylcyclic acid inhibits cyclooxygenase 1 (Cox 1) aka PGH synthase. Inhibition of Cox 1 is irreversible for 8-10 day lifetime of platelets. However, thrmobotic potential exists with 20 % Cox 1 activity so daily ASA is advised. Low doses may be effective because platelets in portal circulation are extensively exposed before degradation (hepatic metabolism, renal excretion).
4 As a vasodilator, dipyridamole should be used cautiously in patients with CAD or hypotension. It lasts half day (extended form) is conjugated to glucuronic acid and excreted via bile into feces.
5. Clopidogrel must be metabolized into an unknown active metabolite by liver.Actions affect dense granule secretion, fibrinogen activity, and coag rate, and TXA2 function. Affects thrombus size and duration but NOT platelet shape. Affects platelet irreversibly. Typically effects are seen within 2 hours, with steady state 40-60 % inhibition at 2-3 days (steady state).