Antiplatelet and Fibrinolytic drugs Flashcards
What is the difference between a thrombus and an embolus?
Thrombus- clot adhered to vessel wall
Embolus - intravascular clot distal to the site of origin
What is the difference between the formation of venous thrombosis and arterial thrombosis?
Venous thrombosis - associated with stasis of blood +/ damage to veins. Less likely to see endothelial damage
Arterial thrombosis - usually form at the site of aatherosclerosis following plque rupture
How do venous thrombosis and arterial thrombosis differ microscopically?
Venous thrombosis - high red cell count and fibrin content, low platelet count
Arterial thrombosis - lower fibrin count, high platelet count
What is the action of prostocyclin in maintaining a healthy endothelium
- Prostocyclin released from endothelial cells inhibits platelet aggregation
- PGI2 binds to platelet receptors, increasing cAMP
- increased cAMP decreases calcium preventing platelet aggregation
- Stabilises GPIIb / IIIa receptors on platelets making them inactive
What factors are released by activated platelets that further activate platelets?
- Thromboxane A2
- ADP
- Serotonin
- PAF (Platelet activating factor)
Activate platelets by activating GPIIb/ IIIb receptors that cause aggregation by binding vWF and fibrin
What class of drugs do you give for platelet rich, arterial thrombi?
Antiplatelets and Fibrinolytic drugs
What class of drugs do you give for low platelet countent, ‘red’ venous thrombi?
Parenteral anticoagulants e.g. heparin
Oral anticoagulants e.g. warfarin
What is the MoA of aspirin?
Inhibitits COX-1 irreversibly, to limit production of Thromboxane A2 from arachidonic acid
How is aspirin absorbed and metabolised?
Absorbed by passive diffusion
Hydrolysed hepatically to salicylic acid
What are some of the side effects of aspirin?
- Prolonged bleeding time - haemorrhagic stroke, GI bleeding (peptic ulcer)
- Reye’s syndrome (hepatic issues) - avoid giving in <16 years
- Hypersensitivity
- Do not use in 3rd trimester pregnancy as closes premature closure of the ductus arteriosus of the fetus
Why does inhibition of platelet aggregation last the lifespan of a platelet (7-10 days)?
Due to irreversible inhibition of COX-1 , platelets lack nuclei so have to wait for new platelets to be made
In what situations would you prescribe aspirin?
- Secondary prevention of stroke and TIA
- Secondary prevention of acute coronary syndromes
- Post PCI and stent procedures to reduce ischemic complications
- Secondary prevention of MI in stable angina/ peripheral vascular disease
What should you give alongside aspirin when it is given long term?
Give PPI for gastric protection
How do ADP receptor antagonists work?
Inhibit binding of ADP to P2Y12 receptors → inhibits activation of GPIIb/ IIIa receptors
Name 3 ADP receptor antagonists
- Clopidogrel
- Prasugrel
- Tricagrelor
Describe the pharmacokinetics of ADP receptor antagonists
- Clopidogrel and prasugrel are irreversible inhibitors of P2Y12 and are pro-drugs
- Clopidogrel needs a loading dose otherwise has slow onset action
- Tricagrelor and prasugrel have more rapid onset
- Tricagrelor acts reversibly at different sites to clopidogrel
What are some of the side effects of ADP receptor antagonists?
- Bleeding, GI upset - dyspepsia and diarrhoea
- Risk of thrombocytopenia (low platelet count)
- Use with caution if renally/ hepatically impaired
When should you give ADP receptor antagonists with caution?
- Clopidogrel requires CYP2C19 for activation
- Omperazole, Ciprofloxacin, erythromycine and some SSRIs inhibit CYP2C19
- Tricagrelor can interact with CYP inhibitors and inducers
- Caution when co prescribed with other antiplatelets and anticoagulants → bleeding
When do you need to stop taking clopidogrel/ tricagrelor before surgery?
Clopidogrel - stopping 7 days prior to surgery
Tricagrelor - stopping 5 days prior to surgery
When are use of ADP receptor antagonists indicated?
- Clopidogrel - monotherapy when aspirin contra-indicated
- NSTEMI patients for up to 12 months
- STEMI with stent for up to 12 months
- Secondary prevention of ischemic stroke/ TIA
What is the only formal way to prescribe tricagrelor?
Tricagrelor + Aspirin
(Liscenced for prevention of atherothrombotic events for up to 12 months)
Explain the mechanism of action of glycoprotein IIb/ IIIa inhibitors
- Inhibits IIb/ IIIa receptors
- Prevents binding of fibrinogen and von Willebrand factors
- Targets the final common pathway → more complete inhibition of platelet aggregation
Name a glycoprotein IIb/ IIIb inhibitor?
Abciximab
How is abciximab administered?
Intravenous injection with bolus dose
