6.2.2 Antiplatelet Drugs and Fibrinolytics Flashcards
What are 3 examples of ADP receptor antagonists?
Clopidogrel
Prasugrel
Ticagrelor
How do ADP receptor antagonists work?
Clopidogrel Prasugrel Ticagrelor
Inhibit binding of ADP to P2Y12 receptor
Inhibits activation of GPIIb/IIIa receptors (independent of COX pathway)
Less aggregation
What are the characteristics of each of the ADP receptor antagonists?
Clopidogrel
Slow onset of action without a loading dose
Irreversible inhibitor of P2Y12
Prasugrel
Fast onset of action
Irreversible inhibitor of P2Y12
Ticagrelor
Fast onset of action
Reversible inhibitor, different site to clopidogrel
All have active hepatic metabolites
What are the adverse effects of ADP receptor antagonists?
Clopidogrel Prasugrel Ticagrelor
Bleeding
GI upset- dyspepsia and diarrhoea
Thrombocytopenia
When should you not use ADP receptor antagonists?
Clopidogrel Prasugrel Ticagrelor
High bleed risk patients
Renal and/or hepatic impairment
What are the important drug to drug interactions with ADP receptor antagonists?
Clopidogrel requries CYPs for activation
CYP inhibitors- omeprazole, ciprofloxacin, erythromycine, some SSRIs
Need to consider use of other PPIs with clopidogrel
Ticagrelor can interact with CYP inhibitors and inducers
Caution when co-prescribing with other antiplatelet and anti-coagulant agents or NSAIDs- increased bleeding risk
How many days prior to surgery should you stop ADP receptor antagonists?
Clopidogrel Prasugrel Ticagrelor
Up to 7 days prior to surgery
When are ADP receptor antagonists used?
Clopidogrel Prasugrel Ticagrelor
Ischaemic stroke
- Clopidogrel long-term monotherapy
- Where aspirin is contraindicated
N/STEMI- aspirin plus
- PCI plus prasugrel unless bleeding risk very high (ticagrelor or clopidogrel)
- No PCI ticagrelor unless bleeding risk very high (clopidogrel)
How long should ADP receptor antagonists be used after N/STEMI?
Clopidogrel Prasugrel Ticagrelor
Usually up to 12 months
What determines the use of ADP receptor antagonists?
Clopidogrel Prasugrel Ticagrelor
Age
Coronary anatomy
Bleed risk
For ACS what is the best ADP receptor antagonist alongside aspirin?
Ticagrelor has faster onset of action
What is an example of a phosphodiesterase inhibitor?
Dipyridamole
How do phosphodisesterase inhibitors work?
Dipyridamole
Inhibits cellular reuptake of adenosine
Increased concentration of adenosine
Inhibits platelet aggregation via adenosine (A2) receptors
Also prevents cAMP degradation, leads to inhibited expression of GPIIb/IIIa
What are the adverse effects of phosphodiesterase inhibitors?
Dipyridamole
Vomiting and diarrhoea
Dizziness
What are the important drug to drug interactions with dipyridamole?
Antiplatelets and anticoagulants
Adenosine
When is dipyridamole used?
Secondary prevention of ischaemic stroke and TIAs
Adjunct for prophylaxis of thromboembolism following valve replacement
Stroke- modified release
What is an example of a Glycoprotein IIb/IIIa inhibitor?
Abciximab
How do glycoprotein IIb/IIIa inhibitors work?
Abciximab
Blocks binding of fibrinogen and von Willebrand factor (vWF)
Targets final common pathway- more complete platelet aggregation
How are Glycoprotein IIb/IIIa inhibitors administered?
Abciximab
IV
What are the adverse drug effects of Glycoprotein IIb/IIIa inhibitors?
Abciximab
Bleeding
Dose adjustment needed for body weight
What are the important drug to drug interactions of Glycoprotein IIb/IIIa inhibitors?
Abciximab
Caution with other antiplatelet and anticoagulant agents
When are Glycoprotein IIb/IIIa inhibitors used?
Abciximab
Specialist use in high risk percutaneous transluminal coronary angioplast patients with other drugs (PCI- stents)
Give two examples of fibrinolytic agents
Streptokinase
Alteplase
What do Fibrinolytic agents do?
Streptokinase Alteplase
Dissolve the fibrin meshwork of a thrombus
How do fibrinolytic agents work?
Streptokinase Alteplase
Converts plasminogen to plasmin which enables degradation of fibrin
When are fibrinolytic agents used?
Streptokinase Alteplase
Acute ischaemic stroke < 4.5 hours from symptoms
Following STEMI acute vs primary PCI
Why can streptokinase only be used once?
Antibodies develop against it
What are the adverse effects of fibrinolytics?
Streptokinase Alteplase
Bleeding
What are the important drug to drug interactions of fibrinolytics?
Streptokinase Alteplase
Antiplatelets and anticoagulants
What is the use of tranexamic acid?
Heavy periods
Opposite effect to fibrinolytics
Inhibition of fibrinolysis
Thrombolysis vs PCI following MI
PCI is preferred with acute STEMI if (some NSTEMI patients) :
- Presentation within 12 hours of onset symptoms
- PRimary PCI can be delivered within 120 minutes of time when fibrinolysis could have been given
What is a negative consequence of PCI?
Reperfusion injury
Reactive oxygen species and Ca2+ to damaged tissue causing increased damage
What is used in secondary prevention of ACS?
Once haemodynamically stable:
- ACEi (ARB is CI)
- Beta blockers
- Dual antiplatelet therapy ~75 mg aspirin + ADP receptor antagonist
- Statin
Plus cardiac rehabilitation e.g. exercise
