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Flashcards in Regulating dopamine levels Deck (33):
1

Describe the structure/pathway of the extrapyramidal motor system?

Three NTs: Ach (excitatory input), DA (tonic inhibition) and GABA 

 

Involves substantia nigra, corpus striatum, cortex and spinal cord

 

Output to skeletal muscle 

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2

Which three NTs are important for motor coordination?

Ach

GABA

DA

3

Describe the motor signs and symptoms of Parkinson's disease?

Tremor

Rigidity

Bradykinesia

Impaired postural reflexes

Facial: impassive, no blinking

Monotonous, hypophonic speech

Decreased dexterity 

 

4

What is PD?

Multisystem neurological disorder which affects cognitive processes, emotion and autonomic function

5

Why are the effects of PD so widespread throughout the body?

Pathology affects the whiole brain > affects the whole individual

6

Describe the non-motor signs and symptoms of PD?

Cognitive deficiencies

Depression 

Increased anxiety

Olfactory deficiencies

Sleep disturbance

Fatigue

Pain

Bowle and bladder problems 

Sexual dysfunction 

7

Which are the first symptoms of PD to appear?

Olfactory deficiencies

Bowel and bladder problems 

8

Which part of the brain degenerates in PD?

Dopaminergic nerves in substantia nigra > decreased DA levels

9

Describe the extent of degeneration of dopaminergic neurons when symptoms of PD begin to appear?

When you start expressing motor symptoms, about 80% of the dopaminergic neurons in the substantia nigra are already dead

10

Which signal transduction pathway is involved in PD?

Various signal transduction mechanisms to deal with Parkinson's

Very complex 

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11

Describe the pattern of degradation of dopaminergic neurons in PD?

Asymmetric

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12

How is PD managed?

No therapeutic cure 

 

Medication > palliative, symptomatic relief

 

13

Describe the rationale behind drug treatment for PD?

Restore DA deficiency:

Increase DA synthesis or release

DA receptor agonists

Reduce DA metabolism

 

Restore dopaminergic/cholinergic balance in striatum:

Cholinergic antagonists

14

Why can't PD just be treated by injecting or orally taking DA?

DA does not cross blood brain barrier

Makes patients violently ill

15

Which drug can be used to increase dopamin synthesis?

How does it work?

Levodopa

L-Dopa + Peripheral DDC inhibitor > prevents metabolism 

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16

What does levodopa require in order to work?

Why is this a problem?

Some functional dopaminergic neurons (need to convert it into dopamine)

Problem because once you flood the system with DA, degeneration of dopaminergic neurons increases

17

Describe the outcome of treatment with levodopa?

Reduces rigidity, tremors and other symptoms

18

What is the first line treatment for PD?

Levodopa

19

What are the disadvantages of levodopa?

Rapid absorption on empty stomach > short half-life (1-2 hours) > patients must constantly medicate, and work out themselves when they need it  > may overdose 

Effectiveness declines over time 

20

Why does the effectiveness of levodopa decline over time?

Continued degeneration of dopaminergic nerves 

21

What is the result of overdosin on levodopa?

Dyskinesias

22

Describe the adverse effects of levodopa?

PERIPHERAL

Anorexia, nausea and vomiting

Tachycardia and ventricular dysrhythmias

Orthostatic hypotension

Pupil dilation

CENTRAL
Hallucinations

Abnormal motor movements

Mood changes, depression, anxiety

 

23

Why are there so many adverse effects associated with levodopa?

Giving extra DA to areas that don't need it 

24

Which dopamine agonists are used in treatment of PD?

How are they used?

Bromocriptine, cabergoline, pergolide

Bromocriptine and cabergoline: monotherapy

Pergolide: only as adjunct to L-Dopa

25

How does entacapone act in the treatment of PD?

Blocks COMT > reduces metabolism of L-Dopa

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26

How does selegiline act in the treatment of PD?

MAOb inhibitor > reduces metabolism of DA

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27

Which drugs can be used to restore the dopaminergic-cholinergic imbalance in PD?

MuscR antagonists

28

What is the alternative treatment to medication in PD?

Deep brain stimulation

Stimulate substantia nigra

29

Describe the role of a-synuclein in PD?

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30

How are mitochondria implicated in PD?

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31

What is the average age of onset of PD?

60

Age is largest risk factor

32

What is the largest risk factor for PD?

Ageing

Weakens mitochondria and reduces neurons' ability to dispose of a-synuclein aggregates

33