PHARM: Stroke Flashcards
2 types of stroke
- ischaemic: occlusion of blood vessel by thrombus or embolus
- haemorrhagic: subarachnoid or intracerebral
which brain area is most vulnerable to ischaemic damage during a stroke?
- hippocampus is most sensitive to oxygen deprivation
ischaemic cascade
- core (cells completely dead): ionic failure, anoxic depolarisation (pumps don’t work so Na+ stays inside = depol), decreased glucose use, glutamate release (causes Ca2+ influx > cell death)
- penumbra (cells still alive but in a ‘silent state’) decreased protein synthesis, acidosis, increased oxygen extraction, selective gene expression
Tx for ischaemic stroke
TARGET OCCLUSION (short term)
- tPA (tissue plasminogen activator) = clot buster, ONLY IF OCCURRED < 4.5 HOURS
- mechanical thrombectomy: stent to remove clot for large vessel occlusions
PREVENT SECONDARY STROKE (long-term)
- anticoagulants e.g. warfarin (oral) or heparin (IV)
- antiplatelet drugs e.g. aspirin, dipyridamole
MOA of rt-PA
- converts plasminogen to plasmin
- plasmin enzyme breaks down clots
when can tPA be given up to 9 hours post stroke?
- usually before 4.5 hours, the core becomes larger than the penumbra = no point in giving tPA
- however in some cases the penumbra (dying area) is still LARGER than the core (already dead) until 9 hours (perfusion mismatch)
- so there is still enough tissue that can be saved to justify the risk of giving tPA
heparin MOA
- anticoagulant (intrinsic pathway)
- combines w/ antithrombin III to neutralise ACTIVATED clotting factors = prevents fibrin formation = prevent clot
- rapid onset and duration
warfarin MOA
- anticoagulant (extrinsic pathway)
- vit K antagonist: interferes w/ activation of clotting factors 2, 7, 9, 10 = decreased fibrin = decreased clots
- long onset and duration
indications + contraindication for anticoagulants
- ischaemic stroke/TIA
- HTN
- existing cardiac disease e.g. AF
- diabetes
- CONTRAINDICATED FOR HAEMORRHAGIC STROKE B/C RISK OF FURTHER HAEMORRHAGE
dipyridamole MOA + contraindication
- antiplatelet for ISCHAEMIC stroke
- inhibits phosphodiesterase > increase cAMP = inhibit platelet aggregation = decreased clots and also vasodilation
- contraindicated in haemorrhagic stroke, unstable angina, hypotension
things to consider when deciding whether or not to treat haemorrhagic stroke
- location of bleed
- age and health of Pt
- surgical risks
Tx + Mx for haemorrhagic stroke
- control high BP to reduce bleeding and prevent future stroke
- usually surgery or osmotic agents to relieve intracranial pressure caused by bleeding
MOA + adverse effects of mannitol
- used to increase plasma osmolarity > water moves out of tissue into blood
- adverse effects: can develop further oedema
anti-platelet vs anticoagulant
- anti-platelet: decrease platelet aggregation to decrease blood clotting
- anticoagulant: target coagulation cascade to decrease fibrin which stabilises clots
Sx of stroke
- vision impairment
- language impairments
- numbness, weakness, paralysis
- dizziness
- swallowing
- headache
