Fibrinolytics and anti-platelets Flashcards
What are the main actions of the fibrinolytic drugs?
Enhancement of fibrinolysis - breakdown of a fibrin thrombosis
What are the 2 classes of fibrinolytics?
- Kinases
* Tissue plasminogen activators (tPA)
Give two examples of kinases
- Streptokinase
* Urokinase
Give three examples of tissue plasminogen activators
- Alteplase
- Tenecteplase
- Reteplase
What are the uses of fibrinolytic drugs?
The breakdown of pathological thrombosis either systemically or locally (catheter directed)
How do tPA derivatives cause the breakdown of a thrombus?
They activate plasminogen, plasmin is then cleaved from plasminogen and breaks down fibrin
How do kinases cause the breakdown of a thrombus?
Bind to plasminogen, releasing plasmin, resulting in the enhanced breakdown of fibrin
Why do kinases pose a significant bleeding risk?
- They act on both the clot bound and free plasminogen
* Causing both fibrinolysis and systemic fibrinogenolysis
What is the issue with streptokinase, which is not an issue with urokinase?
- It is antigenic
* A recent strep infection/ previous use of streptokinase can render streptokinase ineffective
What is the route of administration for kinases?
Bolus dose then infusion
What is the route of administration for alteplase and tenecteplase?
Given as bolus then infusion
What is the route of administration of reteplase?
Bolus only
What are the indications for tPA derivatives?
- Acute myocardial infarction for patients not suitable for primary coronary interventions e.g. angioplasty, within 12 hours of onset of symptoms
- Ischaemic stroke (alteplase), within 4.5 hours of onset of symtoms
- Massive pulmonary embolism with haemodynamic instability (alteplase)
What increases the bleeding risk in those taking tPA derivatives?
- Large ischaemic stroke
- Elderly
- Later administration
- Uncontrolled diabetes
What are the pros of catheter directed thombolysis?
- Smaller doses
- Administered directly into vessel containing thrombosis
- Less systemic effect (although not nay less bleeding)
What are the uses of catheter directed thrombolysis?
- Acute limb ischaemia
- Massive DVT (deep vein thrombosis)
- Blocked CVC (central venous catheter)
What are the actions of anti platelet drugs?
- Inhibits platelet activation
* Inhibit platelet aggregation
How does aspirin work as an anti platelet drug?
Irreversible inhibition of cyclooxygenase, blocking the conversion of arachidonic acid to thromboxane A2, decreasing the platelet activation
How does clopidogrel and ticlodipine work as an anti platelet?
Irreversible blockage of the ADP receptor, deceasing the expression of GPIIb/IIIa, reducing the binding of fibrinogen
What is the mechanism of action of abciximab and tirofiban?
- GPIIb/IIIa antagonists - monoclonal antibodies antagonise the receptor
- Reduced platelet aggregation
- Reduced binding of fibrinogen
What is the mechanism of action of dipyridamole?
- Phosphodiesterase III inhibitor
- Increased platelet concentration of cAMP
- Leading to the decreased platelet responsiveness to ADP
- Reducign the platelet aggregation
What are the indications of anti-platelets?
- Cardiovascular disease
- Acute MI
- Secondary prevention of cardiovascular disease
- Cerebrovascular disease (without AF)
- Acute stroke/TIA/Secondary prevention
- Peripheral vascular
What anti-platelets are used in acute myocardial infarction?
- Aspirin indefinitely
- Ticagrelor/clopidogrel for up to 12 moths
- +/- tirofiban acutely
What anti-platelet is used in secondary prevention of CVD?
Aspirin
What anti-platelet is used in acute stroke/TIA/secondary prevention?
- Clopidogrel
* Dipyridamole + aspirin if clopidogrel not tolerated
