Week 3 - Stroke Flashcards
What is the clinical definition of a stroke?
A syndrome of rapid onset or cerebral deficit (usually focal) lasting more than 24 hours or leading to death, with no apparent cause other than a vascular one
What does an interruption of blood supply cause?
- interruption of blood supply
- cascade of neuronal events
- neurotoxicity –> irreversible necrosis, cerebral oedema and inflammation
What is an occlusion when referring to a stroke?
A lesion with ‘central core’ and ‘ischaemic penumbra’
What is the body’s own clot buster?
Plasmin
- degrades fibrin
- formed locally from plasminogen - trypsin like substance (protease)
What is fibrin?
an insoluble protein formed from fibrinogen during the clotting of blood. It forms a fibrous mesh that impedes the flow of blood.
How is plasmin formed?
Plasminogen is activated by plasminogen activators which diffuse in to thrombus and convert plasminogen to plasmin
Plasmin is localised to the clot… What happens to plasmin that escapes in to the circulation?
Inactivated by plasmin inhibitors
Name some antiplatelet drugs
Aspirin, abciximab, clopidogrel, dipyridamole
What type of stroke is treated with anti-platelet drugs?
Ischaemic stroke
What are the 2 mechanisms of action for anti-platelet drugs?
- inhibit platelet aggregation and thrombus formation by preventing GPIIa/IIIb receptor expression
- preventing GPIIa/IIIb receptor interaction
Even though aspirin is an NSAID, why is it used as an anti-platelet as well?
- inhibits cyclo-oxygenase (COX-1)
- prevents thromboxane formative
-works acutely so given early in first 24hrs and then typically given for 2 weeks
What does dipyridamole do?
-anti-platelet
- inhibits thromboxane synthase
- prevents thromboxane formation
What is dipyridamole often used in conjunction with?
Aspirin
What does clopidogrel do?
- anti-platelet
- antagonise actions of ADP at purinergic (ADP) receptors
What does abciximab do?
- Ab to GPIIb/IIIa receptors
- prevents linking of platelets to fibres
Name some anticoagulant drugs
Antithrombin, heparin, warfarin
Name the different types of strokes
Haemorrhagic - bleed
Ischaemic - blockage - embolism/thrombosis
Transient ischaemic attack - short lived - few mins to 24hrs - complete recovery
Explain what happens in the clotting cascade
Clotting factors - proteins - circulate in the blood
- when blood contacts damaged tissue or exposed collagen - clotting cascade = triggered
- initiated by the activation of factors VIII or XII
- these then activate another clotting factor and so on –> cascade of chemical reactions
- activation of prothrombin (factor II) is a critical step: thrombin converts fibrinogen into fibri
- fibrin = insoluble, stable, traps platelets –> clot formation
What are the various mechanisms of action of anticoagulant drugs?
- activation of antithrombin
- inhibition of vitamin K reductase
- direct (selective)inhibition of steps of clotting cascade (eg direct inhibitors of thrombin)
How is heparin administered?
IV administration as it’s poorly absorbed orally
-works immediately
What is heparin’s mechanism of action?
Activates antithrombin III (present in liver, lungs and mast cells)
-forms complexes with activated clotting factors - thrombin, factors Xa (FIXa and XIa to a lesser extent) - inactivating them
What varies with heparin?
The molecular weight
What are the 2 forms of heparin?
-original unfractionated heparin
-low molecular weight heparin’s
I.e. Heparin fragments - enoxoparin, dalteparin, tinzaparin
What is the mechanism of action of warfarin?
- acts on liver to inhibit enzyme Vitamin K reductase
- enzyme uses vit K to ‘final assemble’ clotting factors II (prothrombin), VII, IX and X
- gradually diminishes concs. of clotting factors
What does warfarin have a similar structure to?
Vitamin k
What must be done when a patient is on warfarin?
-v. complex metabolism in the body so:
Monitoring via INR (international normalised ratio - how much slower is clotting time compared to normal)
-changes because of lots of reasons (e.g diet, drinking, acute illness)
State what a consequence might be of taking warfarin
-interacts with other drugs - drug related adverse effects
Name some thrombin inhibitors
Bivalirudin, lepirudin
What is the mechanism of action of thrombin inhibitors?
- anticoagulants that bind to and inhibit the activity of thrombin and therefore prevent blood clot formation
- inactivate free thrombin and also thrombin that is bound to fibrin
- used to prevent arterial and venous thrombosis
What does bivalirudin do?
- thrombin inhibitor
- helps to prevent platelets in your blood from sticking together and forming a blood clot
- used to prevent blood clots in people with severe chest pain or other conditions who are having an angioplasty done
Given IV
Name some anticoagulant therapy drugs
Protamine sulphate, vitamin k
What does protamine sulphate do?
-combines with heparin to form a stable salt complex which has no anticoagulant activity
What is vitamin K used for?
Treats vitamin K deficiency and to treat certain bleeding/blood clotting problems
Name some thrombotic agents
Alteplase (rTPA), streptokinase, urokinase
What does rTPA mean?
Recombinant tissue plasminogen activators
-recombinant human proteins so non-antigenic
Which drunk is currently licenced for the used in acute ischaemic stroke?
Alteplase
- mist confirm ischaemic event before giving rTPA
- effective only if given within the first 3 hours
Name a systematic haemostatic agent
Aprotinin
What does aprotinin do?
- protease inhibitor - reducing the inflammatory response associated with cardiopulmonary bypass surgery
- reducing blood loss and the need for blood transfusions in patients undergoing certain types of heart/major surgery
