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CT 1 > Parkinson's > Flashcards

Parkinson's Flashcards

(48 cards)

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1
Q

How common is Parkinson’s?

A

2nd most common neurodegenerative disease

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2
Q

What are classic symptoms of Parkinson’s?

A

Tremor
Rigidity
Slowness of movement - Bradykinesia
Balance problems

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3
Q

Causes of Parkinsonian symptoms

A

Parkinson’s disease
Stroke
Infection
Drug Induced - drugs that block dopamine receptors

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4
Q

What is Parkinson’s Disease?

A

Neurodegenerative disease of the basal ganglia and eventually brain stem

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4
Q

Where are neurons lost in Parkinson’s Disease?

A

The substantia Nigra

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5
Q

What % of neurons are lost in Parkinson’s Disease?

A

70-80% of neurons that produce dopamine

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6
Q

Why do other mechanisms occur in Parkinson’s Disease?

A

Compensatory mechanisms for the loss of dopamine

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7
Q

What other levels change in Parkinson’s Disease?

A

Noradrenaline, GABA, S-HT and neuropeptides

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8
Q

What drives tremors in Parkinson’s Disease?

A

Relative increase in ACh

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9
Q

What is dopamine?

A

A neurotransmitter and noradrenaline precursor

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10
Q

What are the 3 main dopaminergic pathways?

A

Motor control - nigrostriatal pathway - facilitates normal movement
Behaviour/emotion - mesocortical pathway
Endocrine/secretion - tuberohyophyseal pathway

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11
Q

What is used to treat tremors in Parkinson’s Disease?

A

Antimuscarnics due to increased levels of ACh

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12
Q

How do dopaminergic drugs work?

A

Increase levels of dopamine in the striatum
- Delivers a precursor to dopamine
- Prevent degradation of dopamine at the neurons
- Stimulates dopamine receptors

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13
Q

What do dopaminergic drugs improve?

A

Improve bradykinesia and reduce rigidity

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14
Q

How does dopamine replacement therapy work?

A

Dopamine precursor DOPA is used

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15
Q

Why is a dopamine precursor used?

A

Dopamine does not cross the BBB

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16
Q

What does Levodopa depend on and why?

A

Some dopa decarboxylase remaining in the striatal neurons as they break down l-dopa to dopamine

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17
Q

What does Levodopa help with?

A

Improvement in initiating and stopping movement
Smoother, faster and more controlled movement
Speech

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18
Q

Side Effects of Levodopa

A

Nausea and vomiting
Postural hypotension and cardiac arrhythmias
Psychiatric disturbances
Urine color change due to metabolic biproduct
GI bleeding

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19
Q

What breaks down dopamine?

Study These Flashcards
A

COMT is an intra- and extra- cellular enzyme that breaks down dopamine to HVA

20
Q

What is dopamine broken down into?

Study These Flashcards
A

Homovanillic acid HVA

21
Q

What does COMT do?

Study These Flashcards
A

Breaks down dopamine to regulate dopamine levels to prevent overstimulation of dopaminergic pathways

22
Q

How does COMT work with L-Dopa?

Study These Flashcards
A

Breaks down L-Dopa to an inert substance to reduce the amount of active dopamine in peripheral tissue

23
Q

What does drug therapy in Parkinson’s Disease aim to do?

Study These Flashcards
A

Increase dopaminergic activity and reduce the relative cholinergic overactivity to restore balance in the basal ganglia

24
Examples of anti muscarinic drugs
Orphenadrine, trihexyphenidyl and benztropine
25
Why are antimuscarinic drugs used?
To reduce tremor in Parkinson's Disease and Parkinsonian symptoms
26
Side effects of antimuscarinic drugs
Peripheral - dry mouth, constipation and urinary retention Central - confusion, euphoria and insomnia
27
What does a loss of dopamine inhibition alter?
The output of the complex basal ganglia circuitry
28
The pathway of Levodopa
Taken up by the remaining dopaminergic neurons in the substantial nigra Converted to dopamine by neuronal Dopa Decarboxylase (DDC)
29
Where is dopamine stored and why?
In the synaptic vessels which protect dopamine from degradation. It stores dopamine to act as a buffer to ensure that dopamine is available for release when needed
30
What is phasic dopamine release?
Dopamine is released in response to specific stimuli
31
What is tonic dopamine release?
Sustained, low-level dopamine release
32
How much of Levodopa is lost to the periphery?
99%
33
How does Levodopa cross the BBB?
By amino acid transporters including LAT1 and SLC7AA
34
What does the BBB consist of?
endothelia, glia and pericytes that work to prevent free diffusion
35
What is given to reduce peripheral side effects?
Peripheral dopa decarboxylase inhibitor
36
Co-Careldopa
Levodopa and Carbidopa Reduces peripheral side effects by reducing conversion to dopamine in the periphery. More Levodopa also gets to the BBB Carbidopa doesn't cross the BBB
37
What do peripheral DDC inhibitors do?
Reduce peripheral side effects and increase the half life of Levodopa
38
1st Line for Parkinson's Disease
Levodopa and DDC inhibitor Oral or transdermal dopamine agonists Mono-amide oxidase B inhibitor
39
2nd Line for Parkinson's Disease
Anticholinergics - young people with severe tremor Beta-adrenergics agonists - for postural tremor
40
What D do dopamine agonists usually affect?
D1, D2 and D
41
Dopamine agonist side effects
Excessive daytime fatigue Peripheral oedema Hallucination and confusion Nausea and vomiting
42
What is dopamine disregulation syndrome?
Uncommon disorder in which dopamingeric medication is associated with behaviours such as pathological gambling, hyper sexuality and stereotypical motor acts
43
What is different about ergot dopamine agonists?
Specific side effects Cannot be used in patients with risk of heart valve issues due to cardiac valvulopathy Cannot be used in patients with serosal fibrosis
44
What tests are required before beginnging treatment with ergot dopamine agonists?
Regular ECGs Blood tests Echocardiograms Chest x-rays for serosal fibrosis
45
Long term problems in Parkinson's Disease
Progressive decline in efficacy of drug therapy Fluctuations in motor performance Psychiatric symptoms
46
What are MOA-B inhibitors?
Reduce breakdown of dopamine
47
When are COMT inhibitors used?
Used alongside Levodopa in late disease progression

CT 1 (11 decks)

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