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Antiplatelet Agents

A visual summary of antiplatelet agents.

COX inhibitors Aspirin-Thrombotic events happen when platelet rich thrombus forms in atheromatous arteries and occludes circulation.Irreversibly inhibits Platelet Cyclo-oxygenase (Key enzyme in platelet biosynthesis pathway of TxA2).Thromboxane A2 
( platelet activator & potent vasoconstrictor).Prolongation of skin bleeding time Fails to prevent aggregation induced by thrombin Only partially inhibits that induced by ADP and high dose collagen Effect lasts about 10 days ( lifespan of platelet ) Coagulation tests are unaltered. Adverse effects-Gastric erosion and GI bleeding (due to inhibition of prostaglandin synthesis ) GI effects are dose related Hypersensitivity reactions as -eg Exacerbation of asthma ( 1 in 20 asthma sufferers can be 
sensitive ) Intracranial haemorrhage

ADP Antagonists – Platelet adenosine diphosphate P2Y (12) receptor antagonists

THIENOPYRIDINE DERIVATIVES Block binding of ADP to its platelet receptor 
( ADP is powerful inducer of platelet aggregation ) Interfere with ADP mediated activation of glycoprotein IIb-IIIa complex Irreversibly inhibit platelet aggregation No effect on prostaglandin metabolism Do not affect coagulation profile ( ie PT and PTT minitoring is not required )

Clopidogrel-similar safety and tolerability and effectiveness as aspirin Used in patients who cannot tolerate aspirin Most common SE is bleeding Advantageous in combination with aspirin than aspirin alone in Non-ST elevation MI Given to pts after stent insertion during PCI Proven useful in prevention of ischaemic stroke , myocardial infarction and vascular deaths in people with symptomatic atherosclerosis

Ticlodipine-Indicated in recurrent cerebral ishcaemia and stroke as an alternative to aspirin Serious SEs have limited usage including TTP and potentially fatal neutropaenia Replaced by clopidogrel ( considered safer and faster acting )

Prasugrel-Is a pro-drug and requires metabolism by cytochrome P450 dependent pathway in liver to be active Less dependent than clopidogrel on hepatic P450 for its activation
ie quicker onset of action , higher degree of in vivo platelet inhibition Less inter-individual variation in response Used only when faster onset of action required for eg immediate PTCA needed or pts with high risk of arterial thrombosis or stent occlusion

Avoid thienopyridines in severe liver dysfunction Avoid Prasugrel in aged > 75 or Body wt < 60 ( ^^ risk of bleeding ) Avoid prasugrel if previous h/o TIA/CVA ( ^ risk intracranial bleeding ) Use of PPIs remains controversial ( conflicting data – potential to inhibit cytohrome P450 mediated activation of Clopidogrel ) Avoid thienopryridines with anti-coagulants ( ^ risk bleeding ) Increased risk bleeding with NSAIDs ( note necessarily contraindicated- assess individual bleeding risk )

Ticagrelor-has some pharmacokinetic advantanges over clopidogrel and prasugrel Is not a pro-drug- does not need hepatic transformation Unlike Clopidogrel and Prasugrel the inhibition is reversible Licenced by NICE in conjunction with low dose aspirin for upto 12 months in adults with ACS ( ie STEMI , NSTEMI or unstable angina requiring imminent PCI ) Recommendations based on PLATO (Platelet inhibition and Patient Outcomes ) trial

PHOSPHODIESTERASE Inhibitor- DIPYRIDAMOLE In patients with IHD – in combination with aspirin not found to be better than aspirin alone
 However in patients with Cerebrovascular disease ESPS-2 study (European Stroke Prevention Study ) demonstrated co-prescription with Aspirin ^^ effective in preventing stroke than either drug alone
 Headache -known SE most common reason for stopping prematurely ( headache is usually transient in nature )

Glycoprotein (GPIIb / IIIa ) Antagonists Glycoprotein IIb/IIIa is a receptor located on platelet membrane -mediates platelet aggregation 
(final common pathway of platelet aggregation )

The receptors recognise an Arginine-glycine-aspartic acid sequence ( RGD ) contained in adhesive molecules as Fibrinogen and Von-villerbrand Factor Abciximab , eptifibatide, tirofiban

Intravenous use in patients undergoing PCI with or without stenting Used in specialist units Medical management of ACS ( roles less certain ) Acute MI ( ajunct to lytic Rx and for primary PCI -role less certain)


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