Cerebrovascular pharmacology

Question 1

Strokes are frequent

Answer 1

• 452 people in Germany have a stroke each day
• about 1 million people live with the sequela of a stroke

Question 2

Stroke -> Definition

Answer 2

Stroke =
– Disturbance in the blood supply of the brain – Sudden onset
– Functional deficit
– Loss of brain tissue

Question 3

the symptoms of stroke depend on the brain areas that are ischemic

Answer 3

• movements
• vision
• language

Question 4

Symptoms of stroke

Answer 4

• 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)

Question 5

One-sided paresis or paralysis

Answer 5

hemiparesis

Question 6

One sided deficit in the field of vision

Answer 6

homonymous hemianopsia

Question 7

TIA (transient ischemic attack) “ministroke”, “transient stroke”, “warning stroke”

Answer 7

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

Question 8

Different form of hemorrhages

Answer 8

• intracerebral hemorrhage
• subarachnoid hemorrhage
• hemorrhagic transformation of a stroke
• subdural hematoma

Question 9

forms of ischemic stroke

Answer 9

• microvascular
• macrovascular
• cardiac embolism

Question 10

Risk factors

Answer 10

IN ABSTEIGENDER REIHENFOLGE
- age
- male gender
- relatives of 1st degree
- sedentary lifestyle
- arterial hypertension
- diabetes mellitus
- high cholesterol
- smoking
- alcohol abuse
- atrial fibrillation

Question 11

Treating arterial hypertension for the primary and secondary prevention of stroke

Answer 11

• 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

Question 12

What is a normal blood pressure?

Answer 12

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

Question 13

Inhibiting blood coagulation by direct oral anticoagulants

Answer 13

• Rivaroxaban
• Dabigatran

Question 14

Inhibiting blood coagulation by vitamin K antagonists

Answer 14

• S-warfarin
• R-warfarin

Question 15

Treatment of acute stroke

Answer 15

• Thrombolysis
• Fibrinolyse

Question 16

Brain hemorrhage after thrombolysis

Answer 16

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

Question 17

Evidence based stroke treatment

Answer 17

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

Question 18

Penumbra

Answer 18

tissue at risk

Question 19

Glucose paradox: potential explanations

Answer 19

• impaired recanalization
• decreased reperfusion
• increased reperfusion injury
• direct tissue injury

Question 20

Metabolism of ketone bodies

Answer 20

Active pathways
1. Fatty acid oxidation
2. Formation of ketone bodies
3. Gluconeogenesis
4. Ketone bodies
5. Citric acid cycle
6. Oxidative phosphorylation

Question 21

Ketogenic diet

Answer 21

• 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