Session 7 Antiplatelet And Fibrinolytic Drugs Flashcards
What is a thrombus?
A clot adhered to vessel wall
What is an embolus?
Intravascular clot distal to site of origin
Compare venous thrombosis and arterial thrombosis
What they are associated with
Fibrin content
Platelet content
Cells etc
VENOUS =
- associated with stasis of blood and/or damage to the veins (less likely to see endothelial damage!)
- HIGH RBC
- HIGH fibrin content
- LOW platelet content
ARTERIAL =
- usually forms at side of atherosclerosis following plaque rupture
- LOWER fibrin content
- HIGH (much higher!) platelet content
What substance that is released and produced by endothelial cells inhibits platelet aggregation?
Prostacyclin
How does prostacyclin (PGI2) inhibit platelet aggregation?
It binds to platelet receptors which increases the concentration of cAMP in platelets
This is coupled with a decrease in platelet aggregatory agents
Stabilise (keeps inactive) GPIIb/IIIa receptors :)
NB: this occurs in healthy endothelium
What do antiplatelet and fibrinolytic drugs target?
Platelet rich “white” arterial thrombi
What do parenteral anticoagulants and heparins/warfarin etc target?
lower platelet content “red” venous thrombi
Give a name of a drug that is an example of a cyclo-oxygenase inhibitor
Aspirin
How is TXA2 formed and what is it? (Thromboxane A2 = TXA2)
TXA2 is a potent platelet aggregating agent
It is formed from arachidonic acid by COX-1
Aspirin inhibits this!
How does aspirin work?
It inhibits the COX-1 mediated production of TXA2 (and so reduces platelet aggregation = IRREVERSIBLE!) - acetylation of CO
TXA2 is formed by COX1 and is a potent platelet aggregating agent
What are
Low doses of aspirin used for?
Low dosing = antiplatelet effects (75mg)
What do higher doses of aspirin do?
Higher doses inhibit endothelial prostacyclin (PGI2)
- imbalance!
how is aspirin absorbed?
Passive diffusion
Hepatic hydrolysis to salicylic acid
What are the warnings / side effects of Aspirin?
- Bleeding time prolonged - Haemorrhagic stroke, GI bleeding (peptic ulcer)
- Reye’s syndrome (avoid if under 16 y.o) - can occur after a viral infection - can be fatal
- Hypersensitivity
- 3rd trimester of pregnancy - aspirin can lead to early closure of the ductus arteriosus!
Need to take these things into account and weight up benefit vs risk
Contradictions of Aspirin?
Other antiplatelet and anticoagulants (additive/synergistic actions)
Why does inhibition (caused by aspirin) last lifespan of platelet? (7-10 days)
Lack nuclei so unable to produce more COX
When would we use aspirin?
- 2nd prevention of stroke, TIA, ACS, MI in stable or peripheral vascular disease
- post primary percutaneous coronary intervention and stent to reduce ischaemic complications
- loading dose in ACS - chewable! (300 mg)
What are 3 drugs that are ADP receptor antagonists?
Clopidogrel
Prasugrel
Ticagrelor
How do ADP receptor antagonists work?
Which ones are reversible or irreversible?
Which ones have slow onset of action and which ones have a fast onset of action?
They inhibit the binding f ADP to P2Y receptor SO inhibit the activation of GPIIb/IIIa receptors
(Independent of the COX pathway)
Clopidogrel and prasugrel are: irreversible inhibitors and prodrugs
Ticagrelor acts reversible at different site to clopidogrel
Clopidogrel has a slow onset of action without loading dose
But
Prasugrel and ticagrelor have more rapid onset
Warnings / side effects of ADP receptor antagonists?
Bleeding! GI upset - dyspepsia and diarrhoea which can lead to thrombocytopenia
Caution - renal and hepatic impairment
Contraindications of ADP receptor antagonists
Clopidogrel requires CYPs for activation (so think of the things that inhibit CYPs such as SSRI’s)
Ticagrelor can interact with CYP inhibitors and inducers
Caution when co prescribed with other antiplatelets and anticoagulants
If someone is having surgery and is taking clopidogrel and/or ticagrelor, what do we do?
Stop clopidogrel 7 days prior to surgery
Stop Ticagrelor about 5 days prior to surgery
Indications for ADP receptor antagonists?
Often used where aspirin is contraindicated in mono therapy
If someone has had a Non-STEMI (up to 12 months after)
If someone has has a STEMI and has a stent (up to 12 months after)
ACS patients (with aspirin)
Balance between CV events and bleeding risk
Name of a glycoproteins IIb/IIIa inhibitor?
Abciximab
How do glycoprotein IIb/IIIa inhibitors work?
Abciximab
Blocks binding of fibrinogen and vWF
(Targets final common pathway!)
The abciximab antibody blocks glycoprotein IIb/IIIa inhibitors
(>80% reduction in aggregation)
Given IV w/ bolus
Warnings of abciximab (glycoprotein inhibitor)
Bleeding!!!!!!!
Dose needs to be adjusted for body weight
Thrombocytopenia, hypotension and bradycardia are also side effects
Contradictions of glycoprotein inhibitors? (Abciximab)
Caution with other antiplatelet and anticoagulant agents
NB: specialist use in high risk percutaneous transluminal coronary angioplasty patients
Name of a phosphodiesterase inhibitor?
Dipyridamole
How do phosphodiesterase inhibitors work?
Inhibits cellular reputable of adenosine
This will increase plasma adenosine
Adenosine will inhibit platelet aggregation via A2 receptors
Warnings / side effects of phosphodiesterase inhibitors?
Flushing, headache and hypersensitivity
Contraindications of phosphodiesterase inhibitors?
Caution with antihypertensives, antiplatelets ad anticoagulants
Uses of phosphodiesterase inhibitors?
Secondary prevention of ischaemic stroke and TIA’s
Adjunct for prophylaxis of thromboembolism following valve replacement
What are some examples of fibrinoltic agents?
I.e. clot busters
Streptokinase
Alteplase
Problems with streptokinase?
Can only be used once as antibodies develop
What is tranexamic acid used for?
Slows the breakdown of clots
I.e. stops fibrin clot —> fibrin degradation products
What are the downstream consequences of dipyridamole’s phosphodiesterase inhibiting action?
Prevents cAMP degradation so I hit s expression of GP IIb/IIIa
