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Antiplatelet agents for the treatment and prevention of atherothrombosis

Antiplatelet drug is a generic term, these are drugs used to decrease platelet aggregation and inhibit thrombus formation. They are most effective for arterial clots that are rich in platelets.

Platelets play crucial role in haemostasis and the development of arterial thrombi. Damaged endothelium activates platelets and they respond by adhering and aggregating. They release thromboxane A2 and adenosine diphosphate (ADP) that amplifies and propagates the process by stimulating surrounding platelets. The production of thrombin via the coagulation cascade is also accelerated, helps in stabilising the thrombus by the conversion of fibrinogen to fibrin. Different classes of antiplatelet drugs act at different junctures in this process.

Aspirin (ASA)

ASA is an antiplatelet agent widely used in the management of acute coronary syndromes (ACSs) and acute ischemic stroke. Other clinically useful effects of ASA are anti-inflammation and antioxidation. ASA is typically used alone or in combination with thienopyridines to manage ACSs or prevent stent thrombosis. This is an indirect thombaxane inhibitor,it irreversibly inhibits the platelet cyclooxygenase (COX)-1 enzyme. ASA, if given at low doses,specifically inhibits plateletsynthesis of thromboxane A2 and this will leads to antithrombotic effect. At medium doses aspirin inhibits both COX-1 and COX-2 by blocking the prostaglandin synthesis and it has analgesic and antipyretic effects.This is why ASA at high doses is effective as an anti-inflammatory drug in treating rheumatic disorders.
However, ASA is a weak inhibitor of platelet aggregation when compared to other antiplatelet medication so typically it is used in combination with other antiplatelet drugs. It is conveniently dosed for once a day and recommended to be taken with food to reduce the gastrointestinal side effects.

Clopidogrel is a thienopyridine ADP-receptor antagonist which irreversibly binds to the P2Y12 receptor.An ADP receptor antagonist that competitively inhibits ADP from binding to platelet receptors, preventing ADP-mediated up-regulation of glycoprotein (GP) IIb/IIIa receptor, again blocking amplification of platelet aggregation. Clopidogrel, is administered orally once a day, this may have variable responses and has a delayed onset of action from 2 to 6 hours if clopidogrel is given as a loading dose of 600 mg onset of action is 12 to 24 hours .There is chance of drug interaction if. used with proton-pump inhibitors (PPIs).
Clopidogrel is used alone in those who cannot tolerate aspirin prophylaxis.
Clopidogrel is routinely used in the treatment of acute coronary syndrome (ACS) and post-percutaneous coronary intervention (PCI) stenting in conjunction with aspirin.

Prasugrel is a prodrug from the same family as clopidogrel, with more efficient platelet inhibition, a thienopyridine that inhibits the ADP receptors on the platelets, hence preventing them from aggregating and causing blood clots. It will irreversibly binds to the P2Y12 receptor. Thienopyridine group of drugs are more potent than ASA.. Prasugrel is given by mouth once a day, beginning with a loading dose and followed with maintenance doses. Prasugrel is the newest thienopyridine drug and it does not have similar concerns of decreased efficacy in those patients who are poor metabolizers or are using concurrent PPIs.
Prasugrel is used in combination with aspirin in ACS patients undergoing primary PCI when:
Immediate PCI is necessary for ST-segment elevation myocardial infarction (STEMI); or
Stent thrombosis occurred during treatment with clopidogrel or
The patient has diabetes mellitus.
This combination is recommended for 12 months only - beyond which there is doubtful clinical benefit.

Dipyridamole act by inhibiting the activity of adenosine deaminase and phosphodiesterase, this will result in accumulation of adenosine, adenine nucleotides, and cyclic adenosine monophosphate. Dipyridamole further inhibits platelet aggregation and leads to vasodilation. This is usually used in ombination with other anticoagulants to prevent thromboembolic complications after surgery. The problem of using dipyridamle is inconvenience, because of multiple doses administered by mouth per day. Dipyridamole is also available in combination with ASA under the brand name Aggrenox and is used to derease the risk of stroke. Aggrenox is usually given by mouth twice daily.It is also used as a stress test agent.
Since Dipyridamole also has vasodilating properties this is unsuitable for use in those with severe coronary artery disease, unstable angina, recent myocardial infarction or left ventricular outflow obstruction

Ticlopidine is one of the first antiplatelet drugs available, is a platelet aggregation inhibitor and is usually used to reduce the risk of thrombotic stroke and administered by mouth two times a day. Ticlopidine was once routinely used but has been falling out of favor because of serious hematological side effect profiles 

Glycoprotein IIb/IIIa antagonists
These drugs inhibit the final common pathway of platelet aggregation where fibrinogen binds to GP IIb/IIIa receptor.Abciximab ,Eptifibatide,Tirofiban
All these drugs require intravenous administration under specialist supervision with close monitoring, usually on coronary care units (CCUs).
Thromboxane A2 and ADP are just two of over 90 known platelet agonists. Blockade by aspirin and clopidogrel will not affect the platelet's ability to be stimulated by other agonists while use of a GP IIb/IIIa antagonist should inhibit aggregate formation whatever agonist influences the platelet.
Since there is chance of neutralising antibodies to abciximab is formed  it can only be used once.
GP IIb/IIIa antagonists can cause severe bleeding, most common from the site of femoral puncture for percutaneous transluminal coronary angioplasty (PTCA). It may take over 12 hours for platelet function to be restored after stopping this infusion

This is licensed for use with aspirin in preventing atherothrombotic events in ACS for 12 months, and is recommended for use for both medical management or where further coronary intervention is planned.