Platelet function is regulated by three categories of substances;
First group consists of agents produced outside of the platelets
and interact with the platelet membrane receptors e.g.
catecholamines, collagen and prostacyclin.
Second group agents produced inside the platelets and interact
with the membrane receptors e.g. ADP. PGD2, PGE2 and serotonin.
Third group agents produced within the platelets and act within
the platelets e.g. thromboxane A2, cAMP, cGMP and calcium ion.
Classification
Mechanism of action
Aspirin
It irreversibly inhibits platelet COX enzymes.Thus no thromboxane
A2 is formed which causes platelets to change shape, secrete
granules and aggregate.Its action lasts for 7-10 days
Mechanism of action
Aspirin in higher doses also inhibits endothelial COX thus
decreasing the formation of prostacyclin PG I2 anti-coagulant.
So aspirin is an anti-platelet agent in low doses only
(325mg/day).
FDA approved for both the primary and secondary prevention of
vascular events in predisposed patients.
Side effects of aspirin
Dipyridamole
Inhibits PDE, increase cAMP, potentiates PGI2, prevent platelet
aggregation.Basically a vasodilator.Used with warfarin (for primary
prevention of thromboemboli in patients with prosthetic heart
valves) and aspirin (for sec prophylaxis of cerebrovascular
diseases).
Cilostazol: a new phosphodiestrase inhibitors that promote
vasodilatation and inhibition of platelet aggregation.
Ticlopidine
Irreversible blockade of ADP receptorInhibits ADP, fibrinogen
induced platelet aggregationIncreased platelet survivalSynergistic
action with aspirinPeak effect 8-10 daysEffect persists several
days after discontinuationUse to prevent thrombosis in patients
undergoing placement of a coronary stent.
Ticlopidine side effects
Neutropenia (1%)Thrombocytopenia (5%)
Haematological monitoring every 2 wks
Diarrhoea, vomiting,dyspepsia and abdominal pain (20%)Headache,
tinnitus, rashBleeding, jaundice
Useful in patients who are resistant to aspirin and
clopidogrel.
Clopidogrel
Congener of ticlopidine, prodrugSafe, better toleratedAspirin +
clopidogrelLess side effect than ticlopidineLess BM toxicity-
neutropenia, thrombocytopeniaAction lasts up to 7 days, once daily
dosing.
GP IIb/IIIa receptor antagonist
Key receptor for platelet aggregationActivation of this receptor
complex is the final common pathway for platelet
aggregation.Receptor for fibrinogen, vWF through collagen,
thrombin, TXA2 and ADP. Block aggregation induced by all
agonists
Abciximab
Chimeric monoclonal antibody against GP receptorApproved for PCI
and in acute coronary syndromesNon antigenicCause thrombocytopenia,
constipation ileus, arrhythmiasExpensive, used in PCI with stent
placement
GP receptor antagonist
Eptifibatidetirofiban
Uses of antiplatelet drugs
Coronary artery disease- MI,unstable anginaPrimary and secondary
prevention of MILow dose aspirin immediately after MIReduce
mortality, prevent reinfarctionContinued indefinitely
