Antiplatelet + Firbinolytic Drugs Flashcards
Compare venous and arterial thrombosis in relation to fibrin + platelet content
- venous: high fibrin, low platelet
- arterial: low fibrin, high platelet
What is virchows triad?
Blood vessel injury
Increased coaguability
Reduced blood flow
Outline how platelet aggregation is prevented in healthy endothelium
prostacyclin produced + released by endothelial cells > inhibition of platelet aggregation:
- PGI2 bind to platelet receptors > increase [cAMP] in platelets > decrease Ca2+
- decrease in platelet aggregatory agents
- stabilises inactive GPIIb/IIIa receptors
Lifespan of platelets
8-10 days
What type of drugs are used in platelet rich ‘white arterial thrombi?
Anti platelets
Fibrinolytic drugs
What types of drugs are used in lower platelet content ‘red’ venous thrombi?
Anticoagulants
What class of drug is aspirin?
Cyclo-oxygenase inhibitor
COX 1
What is the mechanism of action of aspirin?
- irreversibly inhibits COX1 mediated production of thromboxane A2 from arachidonic acid
- reduces platelet aggregation
Why does aspirin not completely inhibit all platelet aggregation?
There are other platelet aggregators
Aspirin only inhibits COX1
What dose is considered baby aspirin?
75mg
Describe baby aspirin
Low dose 75mg
Non analgesic dose
What is the loading dose of aspirin?
300mg
High vs low dose aspirin
high - 300mg
low - 75mg
Action of high dose aspirin
Inhibit endothelial prostacyclin
What are the adverse drug reactions for aspirin?
- GI irritation
- GI bleeding due to ulcer
- Haemorrhage
- Hypersensitivity
What are contraindication of aspirin?
- Reye’s syndrome (avoid <16 years old)
- hypersensitivity
- 3rd trimester pregnancy
Why should aspirin not be given in 3rd trimester of pregnancy?
Premature closure of ductus arteriosus
What are important drug drug interactions of aspirin?
Other anti platelets + anticoagulants
What are uses of aspirin?
- AF patients post stroke
- secondary prevention of stroke + TIA + acute coronary syndromes
- post primary percutaneous coronary intervention
- NSTEMI/STEMI
- pain relief
Examples of ADP receptor antagonists
Clopidogrel
Prasugrel
Ticagrelor
What is the mechanism of action of ADP receptor antagonists?
- Inhibit binding of ADP to P2Y12 receptor
- reduces Ca2+
- this inhibits activation of GPIIb/IIIa receptors
Examples of irreversible ADP receptor antagonists
Clopidogrel + prasugrel
Example of reversible ADP receptor antagonist
Ticagrelor
Route of administration of ADP receptor antagonists
P.O. - oral
Difference in onset of action of different ADP receptor antagonists
slow onset - clopidogrel
fast onset - ticagrelor + prasugrel
What are adverse drug effects of ADP receptor antagonists?
- Bleeding
- GI upset - dyspepsia + diarrhoea
- thrombocytopenia
What is dyspepsia?
Indigestion
What are contraindications of ADP receptor antagonists?
Caution in high bleed risk patients with renal or hepatic impairment
What are important drug drug interactions of ADP receptor antagonists
- Clopidogrel need CYPs for activation (pro drug) - CYP inhibitors e.g. erythromycin, omeprazole
- ticagrelor can interact with CYP inhibitors + inducers
- other anti platelets
- anti coagulants
- NSAIDs
What are uses of ADP receptor antagonists
- ischaemic stroke + TIA
- when aspirin is contraindicated
- NSTEMI/STEMI alongside aspirin
Example of phosphodiesterase inhibitors
Dipyridamole
What is the mechanism of action of dipyridamole?
- Phosphodiesterase inhibitor > prevents cAMP degradation > inhibit expression of GPIIb/IIIa
- Inhibits cellular uptake of adenosine > increased [adenosine] > inhibits platelet aggregation via adenosine receptors
Example of glycoprotein IIb/IIIa inhibitors
abciximab
What is the mechanism of action of GPIIb/IIIa inhibitors?
Blocks binding of fibrinogen + Von Willebrand factor
What are adverse effects of GPIIb/IIIa inhibitors?
Bleeding
What are important drug drug interactions of GPIIb/IIIa inhibitors?
Other antiplatelets + anticoagulant agents
Action of fibrinolytics
Dissolves fibrin meshwork of thrombus > fibrin degradation products
Why does it take 7-10 days for anti platelet effects to cease after terminating aspirin treatment?
- Aspirin is an irreversible COX inhibitor in platelets
- need to wait for the lifespan of these platelets to end (8-10 days) before the effects stop
What tranexamic acid used for?
Stops bleeding
Examples of fibrinolytic agents
Streptokinase
Alteplase
What are adverse effects of fibrinolytic agents?
Bleeding
What is used in the secondary prevention for acute coronary syndrome
Once haemodynamically stable:
- ACEi
- B blockers
- dual anti platelets > 75mg aspirin + ADP receptor antagonist
- statin
+ cardiac rehab
Outline platelet activation and aggregation
- damaged endothelium
- platelets adhere to exposed endothelium
- release of platelet granules e.g. ADP, thromboxane A2, platelts activation factor, thrombin
- activation + aggregation occurs through fibrinogen + GPIIb/IIIa receptors
- increase in Ca2+ + decrease in cAMP in platelets
- amplification from platelet to platelet
- fibrin cap made
What is Reye’s syndrome?
Rare but serious condition causing swelling of liver + brain
What drug class should be co-prescribed with long term aspirin use?
Proton pump inhibitors
For gastric protection
Administration of Abciximab
IV
When can streptokinase be used?
Only once antibodies develop
