Antiplatelets, Anticoagulants And Thrombolysis Flashcards
Give examples of thromboembolic diseases
DVT PE TIA Ischaemic stroke MI AF
What is a thrombus?
A clot adhered to a vessel wall
What in an embolus?
Intravascular clot distal to site of origin
What is a venous thrombosis?
Venous thrombosis associated with stasis of blood or damage to the veins - less likely to see endothelial damage.
High red blood cell and fibrin content, low platelet content evenly distributed.
What is an arterial thrombus?
Usually forms at site of atherosclerosis following plaque rupture.
Lower fibrin content and much higher platelet content.
How does the dug given vary depending on the type and composition of the thrombus?
Platelet rich “white” arterial thrombi - antiplatelet and fibrinolytic drugs.
Lower platelet content “red” venous thrombi -parenteral anticoagulants (heparins..)and oral anticoagulants (warfarin)
A combination of both may be used in some patients often in secondary prevention.
What is particularly important in platelet aggregation?
GPIIB/IIIa surface receptors
How do antiplatelet agents work?
Inhibit platelet aggregation.
Damaged endothelium leads to recruitment of platelets, activation and aggregation at site of injury.
What type of drug is aspirin?
Cyclo-oxygenase inhibitor
How do cyclo-oxygenate inhibitors work?
Potent platelet aggregating agent thromboxane A2 is formed from arachadonic acid by COX-1
Aspirin inhibits COX-1. It reduces TXA2 and inhibits platelet aggregation - irreversible. This only works at a very low (75mg) non-analgesic dose.
How does aspirin work at a higher dose?
Inhibit endothelial prostacyclin (PGI2)- this has a counter effect.
What is the half life of aspirin?
20mins
ADRs of aspirin?
Bleeding time prolonged - haemorrhagic stroke, GI bleeding (peptic ulcer)
What are the indications of aspirin?
Secondary prevention of stroke and TIA if other agents are contraindicated
Secondary prevention of ACS in combination with others.
Post PPCI and stent to reduce ischaemic complications.
Secondary prevention of MI in stable angina or peripheral vascular disease
Inhibition lasts for lifespan of platelet as non-nuclear (7-10 days)
Give examples of ADP receptor antagonists
Clopidogrel
Prasugrel
Ticagrelor
How do ADP receptor antagonists work?
Inhibit binding of ADP to P2Y12 receptor which inhibits activation of GPIIb/IIIIa receptors (calcium mediated)
Describe the characteristics of Clopidogrel
Prodrug - hepatic metabolite with a half life of 7-8 hours.
Irreversible inhibitor
Slow onset of action without loading dose - it can be unpredictable in antiplatelet action
Reduces morbidity and mortality post thromboembolic stoke
Reduces secondary events post MI (with aspirin)
Useful for prophylaxis in patients intolerant to aspirin.
Ticagrelor
Is active and has active metabolites
But , more expensive than clopidogrel
Give examples of glycoproteins IIb / IIIa inhibitors
Abiciximab
Tirofiban
Epitifibatide
All given as IV infusion
How do glycoproteins iiB/IIIa inhibitors work?
Predominant platelet integrin culminating in binding of fibrinogen and VWF.
They target the final common pathway - more complete platelet aggregation.
They are all given IV with a bolus.