Antiplatelet drugs

Introduction

Affects platelet adhesion,

aggregation
Prophylaxis of thromboembolic
disorders
Antiplatelet drugs - arterial
thrombosis
Anticoagulants- venous thrombosis

Introduction
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 anticoagulant.
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 receptor

Inhibits ADP, fibrinogen induced platelet aggregation
Increased platelet survival
Synergistic action with aspirin
Peak effect 8-10 days
Effect persists several days after discontinuation
Use 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, rash
Bleeding, jaundice
Useful in patients who are resistant to aspirin and
clopidogrel.

Clopidogrel

Congener of ticlopidine, prodrug

Safe, better tolerated
Aspirin + clopidogrel
Less side effect than ticlopidine
Less BM toxicity- neutropenia, thrombocytopenia
Action lasts up to 7 days, once daily dosing.

GP IIb/IIIa receptor antagonist

Key receptor for platelet aggregation
Activation 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

receptor
Approved for PCI and in acute coronary
syndromes
Non antigenic
Cause thrombocytopenia, constipation ileus,
arrhythmias
Expensive, used in PCI with stent placement

GP receptor antagonist

Eptifibatide
tirofiban

Uses of antiplatelet drugs

Coronary artery disease- MI,

unstable angina
Primary and secondary prevention of MI
Low dose aspirin immediately after MI
Reduce mortality, prevent reinfarction
Continued indefinitely

Coronary artery disease

Coronary angioplasty,
stents

abciximab + aspirin
Lowers restenosis, stent
thrombosis

stents

Coronary artery bypass

To maintain patency of recanalised

coronary artery
Implanted bypass vessel
Aspirin + ticlopidine / clopidogrel
Abciximab + aspirin + heparin reduce
restenosis
Reduce MI

Coronary bypass implants

Prosthetic heart valves

aspirin + warfarin
reduce microthrombi, embolism

Prosthetic heart valves

Arteriovenous shunts

To maintain the patency of chronic

arteriovenous shunts
For haemodialysis, vascular graft

haemodialysis

Venous thromboembolism

Used prophylactically

Deep vein thombosis

Cerebrovascular disease

Reduce the incidence of TIA

Stroke due to thrombosis

Given in AF

Side effects

Bleeding epistaxis, menorrhagia

Skin rash
Diarrhoea, vomiting, abdominal
pain
Headache, tinnitus
Neutropenia, thrombocytopenia,
jaundice

Antiplatelet drugs &

surgery

Stop treatment 7 days before

surgery
Monitor bleeding time