Therapeutics of basal ganglia Flashcards

1
Q

Where are dopaminergic cells lost from in Parkinsons Disease

A

Substantia Nigra

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2
Q

There is an imbalance between what in Parkinsons disease

A

Direct and indirect pathways

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3
Q

Is the direct pathway more or less active in Parkinson

A

Less

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4
Q

Is the thalamus excited or inhibited in Parkinsons

A

Inhibited

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5
Q

Which 2 structural abnormalities can be seen in Parkinsons

A

Loss of dopaminergic cells in SN

Presence of neurones of lewy bodies

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6
Q

What protein are Lewy bodies enriched with

A

alpha synuclein

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7
Q

What imaging process can be used to monitor dopaminergic nigral cell loss

A

DaT (dopamine transporter) imaging

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8
Q

What can transporter be labelled with in DaT

A

SPECT ligands

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9
Q

What are the features of Parkinsons disease

A
Frozen facial expression
Flexed posure
Altered gait and postural changes
Difficulty in initiating and stopping movement
Resting tremor
Bradykinesia
Rigidity
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10
Q

What is microphagia

A

Increased tendency to smaller illegible handwriting

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11
Q

Name some non motor features of the disease

A
Olfactory dysfunction
Depression
Psychotic symptoms
Cognitive dysfunction
Dementia
Sleep disturbance
Autonomic dysfunction
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12
Q

By how many years may non motor features precede the typical features

A

12-15 years

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13
Q

Name 6 genes involved/ associated with Parkinsons disease

A
SNCA
LRRK2
GBA
PARK2
PINK1
PARK7
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14
Q

What mutation gives the alpha synuclein protein

A

SNCA

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15
Q

Is Parkinson’s incidence and prevalence higher in men or women

A

Women

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16
Q

What does MPTP stand for

A

methyl-phenyl-tetrahydropyridine

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17
Q

What is the compound MPTP transformed into

A

MPP+

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18
Q

What does dysfunction of complex 1 of mitochondrial respiratory chain lead to

A

Oxidative stress

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19
Q

What kind of receptors are G protein coupled receptors

A

Dopamine receptors

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20
Q

What receptors are in the D1 family

A

D1 and D5

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21
Q

What receptors are in the D2 family

A

D2, D3 and D4

22
Q

Name the 5 categories of drugs commonly used to treat Parkinsons disease

A
  • Dopaminergic compounds
  • MAOb inhibitors
  • Anticholinergic compounds
  • Amantadine
  • COMT inhibitors
23
Q

What is L-DOPA

A

Levodopa is a biosynthetic precursor

Combined with peripherally acting DOPA decarboxylase inhibitors

24
Q

Name 2 peripherally acting DOPA decarboxylase inhibitors

A

Carbidopa

Benserazide

25
Q

What dopaminergic agonist can be used as a transdermal patch

A

Ropinirole

26
Q

What dopaminergic agonist can be used as an infusion

A

Apomorphine

27
Q

How do MAOb inhibitors work

A

Protect residual dopamine against oxidation

28
Q

Name 2 MAOb inhibitors

A

Rasagiline

Selegiline

29
Q

Why are anticholinergic compounds used to treat parkinsons

A

Dopamine loss leads to hyperactivity of cholinergic cells

30
Q

Name 3 anticholinergic compounds

A

Orphenadrine
Procyclidine
Trihexyphenidyl

31
Q

How does amantadine work

A

Inhibits dopamine reuptake

Increases dopamine release

32
Q

What drug are COMT inhibitors used with to enhance its effects

A

L Dopa

33
Q

Name 2 COMT inhibitors

A

Entacapone

Tolcapone

34
Q

Name 5 non motor adverse effects of L-DOPA

A
Nausea/ vomiting
Postural hypotension
Psychosis
Impulse control disorders
Excessive day-time sleepiness
35
Q

Name 3 motor complications of L-DOPA

A

On-off effect
Wearing off
Dyskinesia and dystonia

36
Q

Define dystonia

A

Cramps

37
Q

What 3 things must PD patients have regular access to

A

Monitoring and alteration of medication
Continuating point of contact
Reliable source of info

38
Q

What kind of graft can be implanted in PD

A

Human embryonic mesencephalic graft

Functional and releases dopamine

39
Q

What area of the brain can be stimulated in PD

A

Subthalamic nucleus

40
Q

Define chorea

A

Involuntary jerky movements

41
Q

What structural changes occur in huntingtons

A

Major degeneration of striatal neurons and cortical atrophy

42
Q

What protein is involved in Huntingtons disease and what chromosome is involved

A

Huntingtin

Chromosome 4

43
Q

Repeats of what are abnormal in Huntingtons

A

Glutamine/ CAG codon

44
Q

How many repeats of CAG counts as abnormal

A

36

45
Q

In which pathways is there a loss of medium size spiny neurones

A

Striato-pallidal

Striato-nigral

46
Q

What mechanisms undely neurodegeneration in Huntingtons

A
Excitotoxicity
Loss of neurotrophic factors
Accumulation of aggregates of Huntingtin protein
Dysregulation transcription
Increased oxidative stress
Abnormalities in axonal transport
47
Q

Symptoms of Huntington’s disease

A
Choreic movement
Gait abnormalities
Lack of coordination
Cognitive impairment
Psychiatric disturbances
Sleep disturbance
Weight loss
48
Q

What anti depressants can be used in Huntingtons

A

Imipramine

Amitriptyline

49
Q

What antipsychotic drugs can be used in Huntingtons

A

Haloperidol

Olanzapine

50
Q

What sort of drug is tetrabenazine

A

Vesicular amine transporter inhibitor