Cerebrovascular pharmacology Flashcards
Strokes are frequent
- 452 people in Germany have a stroke each day
- about 1 million people live with the sequela of a stroke
Stroke -> Definition
Stroke =
– Disturbance in the blood supply of the brain – Sudden onset
– Functional deficit
– Loss of brain tissue
the symptoms of stroke depend on the brain areas that are ischemic
- movements
- vision
- language
Symptoms of stroke
- Paralysis or paresis plus loss of sensation on one side of the body (partial or complete)
- Drooping mouth
- Deficits in speaking or articulation Impaired language comprehension
- Impaired vision (monocular blindness, deficits in the field of vision, diplopia)
One-sided paresis or paralysis
hemiparesis
One sided deficit in the field of vision
homonymous hemianopsia
TIA (transient ischemic attack) “ministroke”, “transient stroke”, “warning stroke”
After stroke:
Risk of stroke in 90 days -> 2-7 %
After TIA:
Risk of stroke in 7 days -> 4.2 %
Risk of stroke in 30 days -> 6.3 %
Risk of stroke in 90 days -> 10-20 %
Risk parameters: high age, diabetes, duration of symptoms > 10 min., paresis, aphasia
Different form of hemorrhages
- intracerebral hemorrhage
- subarachnoid hemorrhage
- hemorrhagic transformation of a stroke
- subdural hematoma
forms of ischemic stroke
- microvascular
- macrovascular
- cardiac embolism
Risk factors
IN ABSTEIGENDER REIHENFOLGE
- age
- male gender
- relatives of 1st degree
- sedentary lifestyle
- arterial hypertension
- diabetes mellitus
- high cholesterol
- smoking
- alcohol abuse
- atrial fibrillation
Treating arterial hypertension for the primary and secondary prevention of stroke
- Lowering mean arterial blood pressure by 6-10 mm Hg reduces the stroke risk by 50% (primary prevention)
- Elderly patients profit
- Successful also in normotensive subjects
- The blood pressure cannot be too low for stroke prevention
- Lower target blood pressure if there are more risk factors
What is a normal blood pressure?
Usual thresholds: systolic blood pressure < 140 mm Hg, diastolic blood pressure < 90 mm Hg
Even in the normotensive range the blood pressure has an impact on the stroke risk
Inhibiting blood coagulation by direct oral anticoagulants
- Rivaroxaban
- Dabigatran
Inhibiting blood coagulation by vitamin K antagonists
- S-warfarin
- R-warfarin
Treatment of acute stroke
- Thrombolysis
- Fibrinolyse
Brain hemorrhage after thrombolysis
Thrombolysis is only safe in a short time window of 4.5 hours after stroke onset
Thrombolysis at a later time point is afflicted with a higher risk of intracerebral hemorrhage
Evidence based stroke treatment
Treatment of acute stroke
- Thrombolysis < 4.5 h
- ASS < 48h
- Hemicraniectomy
- Stroke unit
Prevention of stroke
- Platelet inhibitors
- Anticoagulation
- Treatment of carotid artery stenosis
- Lowering blood pressure
- Statins
Penumbra
tissue at risk
Glucose paradox: potential explanations
- impaired recanalization
- decreased reperfusion
- increased reperfusion injury
- direct tissue injury
Metabolism of ketone bodies
Active pathways
1. Fatty acid oxidation
2. Formation of ketone bodies
3. Gluconeogenesis
4. Ketone bodies
5. Citric acid cycle
6. Oxidative phosphorylation
Ketogenic diet
- HCA2 mediates neuroprotective effects of ketogenic diet
- HCA2 mediates the effect of nicotinic acid on fat cells
- Nicotinic acid is neuroprotective by activating HCA2
- Flushing by HCA2 activation
- (microglia), monocytes and macrophages express HCA2 -> chimeric mice differentiate between microglia and monocytes/macrophages
- PGD2 mediates the HCA2 effect
