Pharmacology of the Basal Ganglia Flashcards

1
Q

Parkinsons disease pathology;

Where in the brain is dopamine produced? [1]

A

substantia nigra

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2
Q

Which of the following is the substantia nigra?

A

14

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3
Q

Which of the following is the substantia nigra?

A

27

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4
Q

Which of the following is the substantia nigra

A
B
C
D
E

A

Which of the following is the substantia nigra

A
B
C
D
E

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5
Q

What structure is found in neurons that is characteristic of Parkinsons (and other conditions such as dementia)

A

Lewy bodies

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6
Q

Which protein is found in Lewys bodies?

A

protein α-synuclein

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7
Q

Name the staging system used to classify Parkinson’s disease [1]

What is the difference between [] stage 1 & 2 to [] Stage V & VI? [1]

A

The Braak staging of Parkinson’s disease

Braak stage 1 & 2
* pathological changes occur in the medulla oblongata and olfactory bulb

Braak stages 5 and 6:
* the cortical regions eventually become affected

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8
Q

Which stages of Braak staging of Parkinsons are symptoms most likely to develop?

Braak 1 & 2
Braak 3 & 4
Braak 5 & 6

A

Which stages of Braak staging of Parkinsons are symptoms most likely to develop?

Braak 1 & 2
Braak 3 & 4
Braak 5 & 6

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9
Q

What type of imaging can be used to monitor dopaminergic nigral cell loss? [1]

A

dopamine transporter (DaT) - Dat Scan

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10
Q

Describe in detail the classic triad of motor symptoms of Parkinson’s [3]

A

Bradykinesia
* poverty of movement also seen, sometimes referred to as hypokinesia
* short, shuffling steps with reduced arm swinging
* difficulty in initiating movement

Tremor
* most marked at rest, 3-5 Hz
* worse when stressed or tired, improves with voluntary movement
* typically ‘pill-rolling’, i.e. in the thumb and index finger

Rigidity
* lead pipe
* cogwheel: due to superimposed tremor

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11
Q

State 5 non-motor features of Parkinson’s disease

A
  • micrographia
  • olfactory dysfunction
  • depression
  • psychotic symptoms
  • cognitive dysfunction
  • dementia (late phase)
  • sleep disturbance
  • bladder and bowel dysfunction
  • speech and language changes
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12
Q

Describe the difference in onset of symptoms between motor & non-motor Parkinson’s symptoms

A

Non-motor features may precede by 12-15 years: likely to involve regions of peripheral and central nervous system

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13
Q

Describe the difference in onset of symptoms between motor & non-motor Parkinson’s symptoms

A

Non-motor features may precede by 12-15 years: likely to involve regions of peripheral and central nervous system

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14
Q

What is the name for the scoring scales used for disability associated with PD? [1]

What is difference between 0% and 100%? [1]

A

Schwab and England Activities of Daily Living

0%: Vegetative functions
100%: Completely independent - can do chorse without slowness, difficulity or impairment

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15
Q

The genetic link between familial PD is due to a link between which protein? [1] Which gene codes for this protein? [1]

Is PD genetic or environmental? [1]

A

genetic link with the protein alpha-synuclein coded by SNCA (duplications or triplications cause autosomal dominant familial PD)

disease emergence may be due to interactions environment x genes

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16
Q

Describe the link between mitochondrial toxicity and dopaminergic neurons [1]

What process is diruspted as a result of ^ [1]

A

The compound MPTP is a toxin which can be transformed into the metabolite MPP+ which is neurotoxic for dopaminergic neurons

Dysfunction of complex I of the mitochondrial respiratory chain
can lead to increased oxidative stress

17
Q

Which enzyme is critical in the dopamine oxidation process? [1]

What are the products of the dopamine oxidation process? [1]

A

Monoamine oxidase - break down of dopamine can create free radicals (e.g. H2O2

18
Q

COME back to dopminergic pathways in teh CNS

A
19
Q

Describe the mechanism of creation of dopamine [3]

A

L-tyrosine –> L-Dopa (Decarboxylated to create..) –> Dopamine

20
Q

Describe the mechanism of dopamine metabolism [3]

A

Dopamine –> DOPAC –> Homovanillic acid

21
Q

Dopamine binds to which two receptors? [2]

What are the subtypes of these receptors? [5]

A

D1 Family Receptors:
* D1 & D5 subtypes

D2 Family Receptors
* D2, D3 & D4 subtypes

22
Q

Under normal conditions, what does the activation of D1 & D2 receptors cause? [2]

A

D1 receptors are found on the striatal neurons that give rise to the direct pathway: GO pathway

D2 receptors are found on the neurons whose axons form the indirect pathway. NO GO PATHWAY