17 - Parkinson's disease and movement disorders Flashcards

1
Q

What are the main symptoms of Parkinsons Disease

A

Tremor
Rigidity
Bradykinesia
Postural instability

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2
Q

What does death occur as a consequence of in Parkinsons Disease

A

Immobility

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3
Q

What is the cause of PD in the majority of causes

A

Unknown

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4
Q

What are some environmental factors of Parkinsons

A

Pesticides
Heavy metal poisoning
Viral infections
Drugs such as methamphetamine and Ritalin

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5
Q

What may provide protection for DA neuons

A

NSAIDs and caffeine

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6
Q

What is lost in PD

A

Dopamine neurones that project from the substantia nigra

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7
Q

When do symptoms become apparent

A

Reduction of dopamine levels by 80%

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8
Q

What controls the output of GABAergic neurones in the striatum

A

Acetylcholine

Dopamine

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9
Q

ACh causes GABA output to

A

Increase

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10
Q

DA causes GABA output to

A

Decrease

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11
Q

What occurs in PD to GABA output

A

Loss of DA neurones removes inhibitory effect on GABA output leading to increased GABA

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12
Q

What are some other aetiologies that may lead to the same symptoms

A
Toxins
Medications (D2)
Dementia puglistica
Diffuse Lewy Body Disease
Progressive Supranuclear palsy
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13
Q

What is the conversion pathway of dopamine

A

Tyrosine
Dopa
Dopamine

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14
Q

Can dopamine cross the BBB

A

No

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15
Q

Is normal dietary tyrosine sufficient to saturate tyrosine hydroxylase

A

Yes

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16
Q

What is the current treatment for PD

17
Q

How is the percent of L-DOPA crossing the BBB increased

A

Administration of carbidopa

18
Q

What is the on-off effect of L-DOPA

A

L-DOPA effectively treats symptoms initially
By 5 years - 50% have severe symptoms
By 10 year s- 90%

19
Q

What do PD symptoms oscillate between

A

Dyskinesia and akinesia

20
Q

How can the drug regimen be fine tuned

A

More frequent doses at reduced concentrations

21
Q

What is the main action of DA agonists

A

Direct stimulation of D2 receptors in striatum

22
Q

What are two ergot derivative DA agonists

A

Bromocriptine

Pergolide

23
Q

What are benefits of non-ergot derivatives

A

Less likely to induce dyskinesias

24
Q

What are the main side effects of DA agonists

A

Postural hypotension
Hallucinations
Pulmonary fibrosis

25
How do MAOB inhibitors help
Reduce metabolism of levodopa and dopamine | Increased bioavailability of levodopa so less required
26
What is a a selective MAOBI
Selegeline
27
Why is non-selective MAOAI not advised
Possibility of 'cheese or serotonin effect'
28
What are some muscarinic antagonists
Benztropine Trihexyphenidy Diphenhydramine
29
How do muscarinic antagonists aid PD
Reduce GABAergic output | Help with tremor and rigidity, not as effective as L-dopa
30
What is amantadine
Weak NMDA recepor antagonist
31
Amantadine MOA
Potentiates release of dopamine | Exact mechanism unclear
32
How does amantadine work on DA
Improved all symptoms of PD, without significant side-effects but effects modest and short-lived
33
What is the MOA of MPTP (4)
1) Crosses BBB 2) Converted to MPP+ by MAOB 3) MPP+ is taken up by DAT 4) inhibits oxidative phosphorylation and tyrosine hydroxylase
34
How does MPP+ help with modelling PD
Reproduces most of the symptoms and pathology of PD