Antiplatelets and Fibrinolytics Flashcards
Compare arterial and venous thrombi in terms of fibrin and platelet count
Arterial (at site of atherosclerotic plaque);
- Low fibrin content
- High platelet content
Venous (stasis of blood);
- High fibrin content (and RBC)
- Low platelet content
Describe what happens at a healthy endothelium with regards to platelet aggregation
- PGI2/ Prostacyclin produced by endothelial cells
- PGI2 binds to platelet receptors causing an increase in cAMP
- cAMP inhibits the release of sequestered Ca into platelet’s cytosol, thus reducing platelet aggregation
How does PGI2 affect GP IIb/ IIIa receptors?
Stabilises them
Platelet adhesion-> platelet activation-> platelet aggregation-> platelet plug
What causes platelet adhesion
Exposure of blood to sub-endothelial factors (Collagen, VWF)
Describe platelet activation and aggregation
- Platelets adhere to each other, activate and change shape causing the release of granules (ADP, Thromboxane A2, Thrombin, Platelet Activation factor)
- These act via their respective receptors to increase cytosolic Ca and promote further granule release
- Granules also activate GPIIb/IIIa receptors using fibrinogen, forming bonds between platelets
What drugs are used to treat;
- Platelet rich arterial thrombi
- Low platelet venous thrombi
Arterial- Antiplatelet and Fibrinolytic drugs
Venous- Anticoagulants (parental and oral)
(Can use a combination e.g in secondary prevention)
What colour are arterial and venous thrombi?
Arterial- White
Venous- Red
What is the most potent platelet aggregator factor?
Thromboxane A2 (TXA2)
List 4 antiplatelet drug classes
- Cyclo-oxygenase inhibitors
- ADP receptor antagonists
- Phosphodiesterase inhibitors
- GPIIb/IIIa inhibitors
Is aspirin reversible?
Do we use low or high doses for antiplatelet effects?
No
Low doses (High for analgesic effects)
Higher doses of Aspirin inhibit endothelial PGI2
Describe its absorption and metabolism
Absorbed by passive diffusion, metabolised in liver into Salicylic acid
List 4 ADRs of Aspirin
- GI Irritation
- GI Bleeding (peptic ulcer)
- Haemorrhage (stroke)
- Hypersensitivity
List 3 contraindications of Aspirin
- Reye’s Syndrome (can cause liver and brain damage)
- Hypersensitivity
- Trimester 3 pregnancy (premature DA closure)
List important DDIs of aspirin
Caution with other antiplatelets and anticoagulants
Why may aspirin have a lack of efficacy in some patients?
Due to COX1 polymorphism in individuals
Why does Aspirin not completely inhibit platelet aggregation?
Why does aspirin’s antiplatelet effects last for the entire lifespan of the platelet? (7-10 days)
- Half life of only 20 min, rapidly metabolised-> Salicylic acid (no effect on COX)
- Platelets cannot generate new COX
What aspirin course would you give to patients;
- With a STEMI/ NSTEMI
- With acute ischaemic stroke
NSTEMI/ STEMI: One loading dose of 300mg
Acute ischaemic stroke: 300mg daily for 2 weeks
Why can Aspirin irritate the stomach?
How is this covered against when prescribing long term use of aspirin?
- Inhibit COX1 in gastric mucosa-> Reduced prostaglandin production
- Provide gastric protection (e.g a Proton pump inhibitor)
Clopidogrel, Prasugrel and Ticagrelor are all a member of what class of drugs?
How do these work?
- ADP receptor antagonists
- Inhibit ADP binding to P2Y12 receptor-> Inhibit activation of GPIIb/IIIa receptors-> Inhibit platelet aggregation
List 2 common features of Clopidogrel and Prasugrel
- Are both Prodrugs
- Are both irreversible P2Y12 inhibitors
Compare Clopidogrel, Prasugrel and Ticagrelor with regards to onset of action
Clopidogrel- Slow onset of action, unless initial loading dose given
Prasugrel & Ticagelor- Rapid onset of action
List 2 features of Ticagrelor that are distinguish it from Clopidogrel and Prasugrel
- Is active itself AND has active metabolites
- Reversible action (at a different site to Clopidogrel)
List 3 ADRs of ADP Receptor Antagonists
State 3 contraindications of these drugs
- GI bleeding
- GI Upset (Dyspepsia + diarrhoea)
- Rarely, thrombocytopenia
Caution in patients;
- at high risk of bleeding
- with renal and hepatic impairment
- using other antiplatelets/ anticoagulants
List important DDIs of ADP receptor antagonists
Clopidogrel;
- Avoid drugs that inhibit the CYP enzymes needed to activate (Erythromycin, some SSRIs, Omeprazole, Ciprofloxacilin)
Ticagrelor;
- Interacts with CYP inducers & inhibitors
How many days prior to surgery should Aspirin, Clopidogrel and Prasugrel be stopped?
Why?
7-10 days
Due to their effects being irreversible, can lead to bleeding during surgery
Clopidogrel can be used as a monotherapy, where aspirin is contraindicated.
Suggest courses for NSTEMI and STEMI patients
NSTEMI: up to 3 months
STEMI: up to 4 weeks
Suggest 2 drugs that can be taken with Aspirin in a patient who had an MI, for upto 12 months
Prasugrel and Ticagrelor
What class of drug is Dipyridamole?
In what 2 ways does this drug work?
- Phosphodiesterase inhibitors
- Inhibits cellular reuptake of Adenosine, so increased [plasma adenosine]-> Platelet aggregation inhibited via adenosine A2 receptors
- Inhibits phosphodiesterase, leading to reduced cAMP degradation. Thus inhibits activation of GPIIb/IIIa receptors
List 2 ADRs and DDIs of Dipyridamole
- Vomiting + diarrhoea
- Dizziness
- Use of other antiplatelets/ anticoagulants
- Adenosine
Suggest 2 uses of Dipyridamole
- Secondary prevention of ischaemic stroke/ TIAs
- Adjunct for prophylaxis of thromboembolism following valve replacement
What class of drug is Abciximab?
How does it work?
- GPIIb/IIIa inhibitor
- Blocks binding of Fibrinogen and VWF (more complete as it targets final part of aggregation pathway)
Describe the administration and use of abciximab
- Administered IV
- Used only in very specific circumstances (Percutaneous Transluminal Coronary Angioplasty)
What class of drugs are Streptokinase and Alteplase?
How do they work?
- Fibrinolytic agents/ ‘Clot busters’
- Promote activation of Plasminogen to Plasmin, which breaks down Fibrin
Describe the use of Alteplase and Steptokinase
Steptokinase- Can only be used once as antibodies develop
Alteplase;
- In acute ischaemic stroke <4.5 hours from when symptoms start
- Acutely following a STEMI diagnosis (vs a Primary PCI)
List an ADR and DDI of Fibrinolytic agents
- Bleeding
- Caution with use of other antiplatelets/ anticoagulants
How does Tranexamic acid work?
Suggest 2 uses
- Inhibits Fibrinolysis, thus stopping bleeding
- Nosebleeds
- Heavy, persistent period bleeding
What is Primary PCI (Percutaneous Coronary Intervention)?
Insertion of a Catheter via Femoral artery, though Aorta to reach occluded coronary vessel, where a stent can be placed to leave it patent
When should Primary PCI be used instead of a Fibrinolytic?
Primary PCI saves more muscle tissue
If;
- Presentation is within 2 hours of symptom onset
AND
- Primary PCI can be done within 120 mins of the time where a Fibrinolytic could’ve been given
What do you offer to all patients post MI once haemodynamically stable?
ACE inhibitors
List an ADR and a DDI for abciximab
- Bleeding (dose adjusted for body weight)
- Caution with use of other antiplatelets/ anticoagulants
Name a Cyclo-oxygenase inhibitor
How do these work as antiplatelets?
- Aspirin
- Inhibit COX1, which produces TXA2 from Arachidonic acid (thus reduced platelet aggregation)
