PBL1 - Parkinsons Flashcards

1
Q

Cogwheel rigidity

A

Passive movements that show intermittent resistance as if cogs were moving agains one another.

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2
Q

Confirm Parkinson’s diagnosis by improvement when….

A

L-DOPA given

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3
Q

Basal ganglia: (5)

A
Caudate
Putamen
Globus pallidus
Substantia nigra 
Subthalamic nucleus 
(CPGSS)
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4
Q

Basal ganglia are concerned with …

A

Initiation and maintenance of motor actions

I.e. Decision making

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5
Q

Work with the ….. To scale the strength of the response

A

Supplementary motor cortex

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6
Q

Basal ganglia work with the cerebellum to …

A

Modify movement minute-to-minute

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7
Q

Striatum - input nuclei (+ntm)

A

Caudate and putamen

GLUTAMATE

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8
Q

Output nuclei = (3)

A

Globus pallidus
Sunstantia nigra
Subthalamic nucleus

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9
Q

Output nuclei project to the (2)

A

Ventral lateral and ventral anterior thalamic nuclei

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10
Q

Substantial nigra can be divided into -

A

Substantia nigra pars compacts (dopamine producing cells)
+
Substantia nigra pars reticulata (received input from the striatum and sends it outside the basal ganglia to control head and eye movements

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11
Q

GPi or GPe is the major output nucleus from the basal ganglia to the thalamus?

A

GPinternal

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12
Q

Basal ganglia brake theory:

A

Remain still - inhibit all movements excepts reflexes that keep you still
Move - inhibit some postural reflexes and release voluntary ones

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13
Q

Basal ganglia - series or …. And … Loops which regulate movement.

A

Excitatory and inhibitory

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14
Q

Spiny Neurons are anatomically ….

A

Indistinguishable

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15
Q

Spiny neurons hat express D1 project to the …

A

GPi

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16
Q

Spiny Neurons that express D2 project to the …

A

GPe

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17
Q

Spiny Neurons receive input from the

A

Nigrostriatal pathway

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18
Q
D1 = excitatory / inhibitory
D2 = excitatory / inhibitory
A
D1 = excitatory
D2 = inhibitory
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19
Q

When movement is required, SNpc = topically … And facilitated the … Pathway
This causes …. ….. As the …. Is inhibited, so they …..-…. Cells are free from inhibition

A
Active 
Direct pathway
Double inhibition 
GPi
Thalamic-cortical cells
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20
Q

Parkinson’s - decreased SNpc cells - the …. Pathway then becomes dominant
Leading to inhibition of the …. And decreased activity in the …. Projection

A

Indirect
Thalamus
Thalamocortical projection

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21
Q

NTM:
Striatal Neurons are …… But are activated by …
Corticostriatal pathway and thalamocortial pathway use ….

A

GABAergic activated by dopamine

Glutamate

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22
Q

L-DOPA = converted to dopamine in the ….

A

Remaining dopaminergic cells in the brain

23
Q

MADOPAR

A

L-DOPA + peripheral decarboxylate inhibitory (benserazide) - prevents it being converted outside BBB

24
Q

Dopamine outside of the BBB stimulates…. Which causes….

A

Chemoreceptor trigger zone

nausea and vomiting

25
Q

Complications of long term L-DOPA:

4

A
Motor fluctuations (on/off phenomenon)
Dyskinesia (impaired voluntary movement)
Non motor complications (pins and needles, pain, autonomic dysfunction)
Neuro-psychiatric complications (hallucinations, delirium, mood changes, hyper sexuality)
26
Q

Dyskinesia can be split into … (2)

Due to …

A

Chorea- like movements (hyperkinetic, purposeless dance like movements)
Dystonia’s (intense and sustained muscle contractions)

Due to fluctuations in dopamine levels

27
Q

Motor fluctuations =

A

On / off effect

28
Q

New drugs to target L-DOPA dyskinesia … (4)

A

A-2receptor antagonists,
glutamate receptor antagonists (acting at AMPA, NMDA, Metabotrophic receptors),
5-HT 1a receptor antagonists,
D4 receptor antagonists

29
Q

Entacapone - …

In conjunction with LDOPA good as …

A
Inhibits COMT (catechlol-O-methyl-transferase) 
... Alleviate long term problems of L-DOPA being short lived
30
Q

Dopamine agonists (2)

A

Bromcriptine
Pergolide
(Less efficacy than LDOPA)

31
Q

Rotigotine (2)

A

Dopaminergic agonist

Transdermal patch - 24 hr

32
Q

Parkinson’s co-morbidities (2)

A

Depression

Dementia

33
Q

Initial Parkinson’s treatment (before L-DOPA)

A

Dopaminergic agonists

34
Q

Selegiline (3)

A

MAOb inhibitor
Used to treat mild Parkinson’s symptoms
SE: agitation, hallucinations

35
Q

Benztropine (2)

A

Anti-cholinergic drug

Treat mild Parkinson’s symptoms

36
Q

Amantadine (2)

A

Release dopamine

Treat mild Parkinson’s symptoms

37
Q

L-DOPA + …. - used and get less motor side effects

A

Selegiline

38
Q

Vitamin E

A

Neuro protective effects,

Anti-oxidant (Parkinson’s increases oxidative stress in nervous system)

39
Q
Surgical treatment (not applicable if dementia, or depression present)
(2)
A

DBS of Subthalamic nucleus
OR
Removal of global pallidus (pallidotomy)

40
Q

Micrographia

A

Text gradually gets smaller

41
Q

Parkinson’s epidemiology (2)

A

Higher in smokers

Higher men than women

42
Q

Nigrostrialtal pathway:

A

Substantial Nigeria - corpus striatum

Motor control

43
Q

Mesolimbic pathway

A

VTA - nucleus accumubens and olfactory tubercle

44
Q

Mesocortical pathway:

A

VTA - frontal cortex

45
Q

Tuberoinfundibular pathway:

A

Arcuate nucleus - median eminence

46
Q

Lack of dopamine chases (2)

A

Lack of FOF response

Constipation

47
Q

D1 inhibits /activated adenyl cyclase

D2 inhibits / activated adenyl cyclase

A

D1 inhibits - activated direct pathway - facilitates medium spiny Neurons
D2 activates - activates indirect pathway - inhibits spiny Neurons

48
Q

Tyrosine …. (Enzyme 1 ) …. L-DOPA … (Enzyme 2 )…. Dopamine

A

Tyrosine carboxylase

DOPA carboxylase

49
Q

Dopamine transported by

A

VMAT 2

50
Q

Dopamine degraded to … By …. Or …..

A

DOPAC
MAO
Adenylate cyclase

51
Q

Lewy bodies -

A

Intracellular aggregates of synuclein

Found in dopamine Neurons

52
Q

What can cross the BBB nod is neurotoxic for dopaminergic Neurons?

A

MPTP

Methy phenyl tetraydropine

53
Q

Tremor in Parkinson’s is at ….

A

Rest!