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Neuroscience > Regulating dopamine levels > Flashcards

Regulating dopamine levels Flashcards

1
Q

Describe the structure/pathway of the extrapyramidal motor system?

A

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
Q

Which three NTs are important for motor coordination?

A

Ach

GABA

DA

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3
Q

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

A

Tremor

Rigidity

Bradykinesia

Impaired postural reflexes

Facial: impassive, no blinking

Monotonous, hypophonic speech

Decreased dexterity

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4
Q

What is PD?

A

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

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5
Q

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

A

Pathology affects the whiole brain > affects the whole individual

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6
Q

Describe the non-motor signs and symptoms of PD?

A

Cognitive deficiencies

Depression

Increased anxiety

Olfactory deficiencies

Sleep disturbance

Fatigue

Pain

Bowle and bladder problems

Sexual dysfunction

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7
Q

Which are the first symptoms of PD to appear?

A

Olfactory deficiencies

Bowel and bladder problems

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8
Q

Which part of the brain degenerates in PD?

A

Dopaminergic nerves in substantia nigra > decreased DA levels

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9
Q

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

A

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

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10
Q

Which signal transduction pathway is involved in PD?

A

Various signal transduction mechanisms to deal with Parkinson’s

Very complex

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11
Q

Describe the pattern of degradation of dopaminergic neurons in PD?

A

Asymmetric

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12
Q

How is PD managed?

A

No therapeutic cure

Medication > palliative, symptomatic relief

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13
Q

Describe the rationale behind drug treatment for PD?

A

Restore DA deficiency:

Increase DA synthesis or release

DA receptor agonists

Reduce DA metabolism

Restore dopaminergic/cholinergic balance in striatum:

Cholinergic antagonists

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14
Q

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

A

DA does not cross blood brain barrier

Makes patients violently ill

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15
Q

Which drug can be used to increase dopamin synthesis?

How does it work?

A

Levodopa

L-Dopa + Peripheral DDC inhibitor > prevents metabolism

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16
Q

What does levodopa require in order to work?

Why is this a problem?

A

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
Q

Describe the outcome of treatment with levodopa?

A

Reduces rigidity, tremors and other symptoms

18
Q

What is the first line treatment for PD?

A

Levodopa

19
Q

What are the disadvantages of levodopa?

A

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
Q

Why does the effectiveness of levodopa decline over time?

A

Continued degeneration of dopaminergic nerves

21
Q

What is the result of overdosin on levodopa?

A

Dyskinesias

22
Q

Describe the adverse effects of levodopa?

A

PERIPHERAL

Anorexia, nausea and vomiting

Tachycardia and ventricular dysrhythmias

Orthostatic hypotension

Pupil dilation

CENTRAL
Hallucinations

Abnormal motor movements

Mood changes, depression, anxiety

23
Q

Why are there so many adverse effects associated with levodopa?

A

Giving extra DA to areas that don’t need it

24
Q

Which dopamine agonists are used in treatment of PD?

How are they used?

A

Bromocriptine, cabergoline, pergolide

Bromocriptine and cabergoline: monotherapy

Pergolide: only as adjunct to L-Dopa

25
Q

How does entacapone act in the treatment of PD?

A

Blocks COMT > reduces metabolism of L-Dopa

26
Q

How does selegiline act in the treatment of PD?

A

MAOb inhibitor > reduces metabolism of DA

27
Q

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

A

MuscR antagonists

28
Q

What is the alternative treatment to medication in PD?

A

Deep brain stimulation

Stimulate substantia nigra

29
Q

Describe the role of a-synuclein in PD?

A
30
Q

How are mitochondria implicated in PD?

A
31
Q

What is the average age of onset of PD?

A

60

Age is largest risk factor

32
Q

What is the largest risk factor for PD?

A

Ageing

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

33
Q
A

Neuroscience (51 decks)

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