Anti-platelets and Thombolytics Flashcards
Give some examples of anti-platelet drugs
Aspirin
Di-pyridamole
Clopidogrel
Glycoprotein IIb/IIIa inhibitors
How does aspirin work as an anti-platelet?
Irreversible COX-1 inhibition by covalent acetylation of serine
Stops production of prostaglandin 2 and therefore thomboxane A2
How does clopidogrel work?
Inhibits ADP-dependent aggregation of platelets
Indications of clopidogrel?
Acute coronary syndrome - MI, angina
After a PCI (percutaneous coronary intervention)
How does dipyridamole work as an antiplatelet?
Phosphodiesterase inhibitor
ADRs of dipyridamole and why?
Positive inotrope and vasodilator
- flushes
- headaches
Indication for dipyridamole?
Secondary prevention of stroke
How do glycoprotein IIb/IIIa antagonists work?
Fibrinogen normally binds to these receptors causing platelet aggregation
Antagonists block this final pathway
Name some glycoprotein IIb/IIIa antagonists
Abciximab
Eptifibatide
Tirofiban
Uses of glycoprotein IIb/IIIa receptor antagonists?
High risk acute coronary syndrome
Post-PCI
-increases risk of bleeding compeicatioms but decreases acute thrombosis and re-stenosis
How are thrombi normally cleared?
Plasmin activated from plasminogen cleaves fibrin by binding to fibrin strands within a thrombus
How is plasminogen cleaved to plasmin?
Plasminogen activators
- tissue plasminogen activator (tPA)
- urokinase-type plasminogen activator (uPA)
Activate plasminogen that is bound to fibrin
What regulates the fibrinolytic system?
Circulating inhibitors such as PAI-1
Mechanism of action of streptokinase?
Promotes cleavage in plasminogen to produce plasmin
Why can streptokinase not be used twice in the same patient?
It is a bacterial protein so is antigenic
Generates blocking antibodies which persist for many years leading to allergic reactions
Other ADRs of streptokinase?
Transient hypotension when being infused (slow infusion to increase blood pressure)
Haemorrhage
What is alteplase? Mechanism of action?
A recombinant tPA
Converts plasminogen to plasmin when plasminogen is bound to fibrin - clot-specific as only works in presence of fibrin
Indications for fibrinolytic drugs?
Acute MI
PE
Major venous thrombosis
Ischaemic stroke
Why must fibrinolytics be given within a short amount of time if the event?
Consequence of vascular occlusion can become irreversible
Thrombi become more resistant to lysis so that potential benefit decreases while risk of haemorrhage (stroke) remains the same
How long can fibrinolytics be given given for after an event?
Ischaemic stroke - up to 3 hours
Coronary occlusion - up to 12 hours
Difference between fibrinolytics and thrombolytics?
Fibrinolytics breakdown fibrin inside a thrombus eg streptokinase, alteplase (tPA)
Thombolytics break down the thrombus eg heparin
Criteria for a fibrinolytic therapy to be given to a patient who has had an MI?
Clear evidence from history and ECG of MI within last 12 hours
No contra-indications
Criteria for fibrinolytic treatment in PE?
Clear diagnosis
Significant haemodynamic compromise
Absence of major contraindications
Contra-indications of fibrinolytics?
Active peptic ulcer or other potential bleeding source
Recent trauma/surgery
History of cerebral haemorrhage or stroke of uncertain aetiology
Uncontrolled hypertension
Coagulation defect
Streptokinase should not be given to a patient twice
ADRs with fibrinolytics?
Haemorrhage
- brain
- GI tract
Treatment of severe allergy/anaphylaxis to streptokinase?
Adrenaline Oxygen IV fluids Antihistamine Hydrocortisone
Treatment of a cerebrovascular event after fibrinolytic therapy?
CT or MRI to find out cause
-haemorrhagic - treatment related
-ischaemic - embolus from heart
Both equally likely after MI
Treatment of serious bleeding after fibrinolytic therapy?
Blood transfusion or volume expanders
Inhibition of further fibrinolysis with tranexamic acid or aprotinin
Specific recombinant or pooled clotting factors
What are the different ways that anti-platelets can work?
Stop platelet adhesion
Stop platelet activation
Stop platelet aggregation
