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Block 3 > Basal Ganglia + Pharmacology > Flashcards

Basal Ganglia + Pharmacology Flashcards

1
Q

Draw out the route of the direct pathway

A

See slides

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2
Q

Which receptor does dopamine act on in the direct pathway?

A

D1 receptors

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3
Q

Does the direct pathway promote or inhibit movement?

A

Promotes it

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4
Q

Describe the basic pathology of Parkinson’s disease

A

Less dopamine is released from the SNPC to activate the striatum by acting on D1 receptors in the direct pathway. Less activation of the direct pathway will result in decreased movement and Parkinson-isms

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5
Q

What 2 things make up the striatum?

A

Caudate nucleus

Putamen

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6
Q

What 3 things make up the pallidum?

A

Globus pallidus internus

Globus pallidus externus

Substantia nigra pars reticula

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7
Q

What 3 things make up the lentiform nucleus?

A

Putamen

Globus pallidus internus

Globus pallidus externus

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8
Q

What does the caudate nucleus connect with anteriorly?

A

Putamen

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9
Q

What does the substantia nigra pars compacta do in normal physiology?

A

Promotes movement

Activates direct pathway

Inhibits indirect pathway

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10
Q

What type of signalling does the substantia nigra pars compacta use?

A

Dopaminergic

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11
Q

What is an immediate lateral relation of the thalamus?

A

The internal capsule

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12
Q

Which portion of the thalamus connects the basal ganglia to the premotor cortex?

A

Ventral anterior nucleus

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13
Q

SNPC activates the striatum via…

A

D1 receptors

Direct pathway

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14
Q

SNPC inhibits the striatum via…

A

D2 receptors

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15
Q

Does the indirect pathway promote or reduce movement?

A

Reduces movement

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16
Q

Draw out the indirect pathway

A

See slides

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17
Q

Describe Huntington’s disease

A

Huntington’s causes degeneration of the striatal input to the GPE.

This switches off the inhibition from the GPE to the subthalamic nucleus

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18
Q

What does hyperkinetic mean?

A

Too much movement

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19
Q

What does hypokinetic mean?

A

Too little movement

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20
Q

Name some hypokinetic disorders (5)

A

Parkinson’s

Multiple systems atrophy

Progressive supranuclear palsy

Wilson’s disease (pseudoparkinsonism)

Essential tremor

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21
Q

Name some hyperkinetic disorders (7)

A

Hemiballismus

Huntington’s

Dystonias

Wilson’s disease (dystonic)

Essential tremor

Chorea

Athetosis

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22
Q

Define tremor

A

Shaking movements

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23
Q

Define dystonia

A

Twisting and repetitive movements or abnormal postures

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24
Q

Define athetosis

A

Writhing movements like a snake

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25
Q

Define chorea

A

Twitching or jerking a group of muscles

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26
Q

Define ballismus

A

Large, flinging limb movements

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27
Q

Define tics

A

Small involuntary movements

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28
Q

Which region is involved in Parkinson’s disease?

Which neurotransmitter is affected?

A

Substantia nigra

Reduction in dopamine

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29
Q

Which region is involved in Huntington’s disease?

Which neurotransmitter is affected?

A

Striatum (caudate nucleus + putamen)

Reduction in GABA

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30
Q

What is the inhibitory neurotransmitter in the basal ganglia?

A

GABA

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31
Q

What is the excitatory neurotransmitter in the basal ganglia?

A

Glutamate

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32
Q

Which area in the basal ganglia is thought to be the ‘focal centre’ for the generation of tremors?

A

Globus pallidus

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33
Q

Which 2 areas of the brain, in theory, could be removed in order to treat tremors?

A

Thalamus

Globus pallidus

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34
Q

Name some motor effects of Parkinson’s disease

A

Bradykinesia

Resting tremor

Rigidity (lead pipe, cogwheel)

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35
Q

Name some other features of Parkinson’s (other than motor)

A

Festinating gait

Lack of facial expression

Micrographia

No weakness

Normal reflexes

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36
Q

What is the cause of Huntington’s disease?

A

Genetic

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37
Q

What motor effects are seen in Huntington’s?

A

Choreiform (jerky, involuntary movement)

Clumsy, unsteady gait

Difficulty with speech and swallowing

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38
Q

Name the 3 main groups of Parkinsonism

A

Pure Parkinsonism

  • idiopathetic
  • iatrogenic
  • post-encephalitic

Parkinsonism with extras

  • multiple systems atrophy
  • progressive supranuclear palsy

Pseudoparkinsonism

  • Wilson’s disease
  • benign essential
  • trauma and vascular related
39
Q

What are the 4 cardinal symptoms of Parkinson’s?

A

TRAP:

Tremor (resting)

Rigidity (lead pipe, cogwheel)

Akinesia (bradykinesia)

Postural instability

40
Q

Name 4 additional symptoms of Parkinson’s

A

Micrographia

Mask-like face

Sleep disturbances

Aprosodia

41
Q

What % of substantia nigra is lost at the time of presentation of Parkinson’s disease?

A

Already 60% loss

42
Q

Name the 4 dopamine pathways

A

Nigrostriatal

Mesolimbic

Mesocortical

Tubero-hypophyseal

43
Q

Where does the nigrostriatal pathway go from/to?

A

Substantia nigra to striatum (putamen and caudate nucleus)

44
Q

Where does the tubero-hypophyseal pathway go from/to?

What is its role?

A

Hypothalamus to pituitary

To inhibit prolactin

45
Q

Which dopamine pathway is involved in Parkinson’s?

A

Nigrostriatal pathway

46
Q

Where does the mesolimbic pathway go from/to?

A

Ventral tegmental area to limbic system

47
Q

Where does the mesocortical pathway go from/to?

A

Ventral tegmental area to prefrontal cortex

48
Q

What are the mesolimbic and mesocortical dopamine pathways involved in?

A

Emotions

Thoughts

Higher cortical processes

49
Q

Which dopamine pathways are involved in psychosis?

A

Mesolimbic

Mesocortical

50
Q

What is the main issue in treatment of Parkinson’s disease?

A

Dopamine does not cross the BBB

51
Q

What is the precursor of dopamine?

A

Levodopa

52
Q

What is the gold standard drug for Parkinson’s disease?

A

Levodopa

53
Q

What needs to be considered when prescribing levodopa?

A

Nothing more can be done when maximum dose is reached.

Levodopa is metabolised quickly

54
Q

Which enzyme breaks down L-dopa in the periphery?

A

Dopa-decarboxylase

55
Q

Name a dopa-decarboxylase inhibitor

A

Carbidopa

56
Q

What type of drug is carbidopa

A

Dopa-decarboxylase inhibitor

57
Q

Which 2 enzymes break down dopamine in the CNS?

A

Catechol-O-methyltransferase (COMT)

Monoamineoxidase (MAOI-B)

58
Q

Give an example of a catechol-O-methyltransferase inhibitor

A

Entacapone

59
Q

What class of drugs does entacapone belong to?

A

Catechol-O-methyltransferase (COMT) inhibitor

60
Q

Give an example of a monoamineoxidase (MAOI-B) inhibitor

A

Selgiline

61
Q

What family of drugs does selegiline belong to?

A

Monoamineoxidase (MAOI-B) inhibitor

62
Q

When are dopamine agonists used?

A

Useful in younger patients when you need to prolong treatment

Good first line treatment of Parkinson’s

63
Q

Give an example of a dopamine agonist

A

Pramipexole

64
Q

What class of drug is pramipexole?

A

Dopamine agonist

65
Q

Which dopamine receptor do dopamine agonists primarily work on?

A

D2 receptors

66
Q

What is a main side effect of dopamine agonists?

Which dopamine pathways do they act on to illicit these symptoms?

A

Psychiatric effects: hallucinations, visions etc.

Mesocortical
Mesolimbic

67
Q

Name some side effects of dopamine based treatments

A

Sudden onset sleep

On-off effects

Drowsiness

Psychosis

Hypotension

Tachycardia

Nausea and vomiting

68
Q

What drug is given to fill in the ‘on-off’ effects of Parkinson’s?

A

Apomorphine

69
Q

Name the common side effect experienced with apomorphine

A

Nausea and vomitting

70
Q

What drug is given prophylactically before apomorphine use?

A

Domperidone

71
Q

When are anticholinergics useful in treating Parkinson’s?

A

Iatrogenic (drug-induced) Parkinson’s

72
Q

Why are anticholinergics used to treat Parkinson’s?

A

Because a decrease in dopamine leads to an increase in acetylcholine concentration

73
Q

Name an anticholinergic used to treat Parkinson’s

A

Orphenadrine

74
Q

What class of drugs does Orphenadrine belong to?

A

Anticholinergics

75
Q

What are the 3 forms of Wilson’s disease?

A

Dystonic

Pseudoparkinsonism

Cerebellar

76
Q

What is Wilson’s disease?

A

Hepatolenticular degeneration caused by copper accumulation

77
Q

What sign might you see in a patient with Wilson’s disease?

A

Kayser-Fleischer rings

78
Q

What is the treatment for Wilson’s disease?

A

Copper chelators

Zinc - blocks copper absorption in the gut.

79
Q

Define essential tremor

A

A familial progressive disorder characterised by intention tremor, not present at rest.

Rhythmic tremor 4-12Hz frequency

80
Q

What 2 types of drugs treat essential tremors?

Give an example of a drug from each family

A

Beta- blockers
-Propanolol

Antiepileptic
-Primidone

81
Q

Describe Huntington’s disease

A

Inherited neurodegenerative disorder

Autosomal dominant

82
Q

What 4 types of drugs are used to treat Huntington’s disease?

A

Dopamine depleting drugs

Antipsychotics

Benzodiazepines

Antidepressants

83
Q

Give 4 examples of drugs used to treat Huntington’s and their drug class

A

Tetrabenazine
-dopamine depleting

Risperidone, haloperidol
-antipsychotics

Diazepam
-benzodiazepine

SSRIS/TCAs
-antidepressants

84
Q

Describe the mechanism of action of tetrabenazine

A

Dopamine-depleting drug

Blocks VMAT2 (vesicular monoamine transporter). prevents transport of dopamine into vesicles = less released in the synapse

Affects all monoamines, not just dopamine

85
Q

Why does tetrabenazine cause depression?

A

Because it affects all vesicular monoamine transporters (e.g. 5HT and NA)

86
Q

What 2 diseases are tics seen in?

A

Wilson’s

Huntington’s

87
Q

What are the 3 treatments for tics?

A

Patient education

2nd generation antipsychotics

1st generation antipsychotics

88
Q

What are the 2 main treatments for dystonia?

A

GABA agonists
-Baclofen

BDZ
-diazepam

89
Q

What class of drug is baclofen?

A

GABA agonist

90
Q

How do you treat chorea?

A

2nd generation antipsychotics

Dopamine depleting drugs (tetrabenazine)

GABAergic drugs (anti-epileptics, gabapentin, BDZ)

91
Q

What is athetosis?

A

Slow, irregular, sinous writhing movements

92
Q

What is ballismus?

A

large, violent, proximal, flinging movements of the limbs

If unilateral = hemiballismus

93
Q

What causes ballismus?

A

Neurodegeneration of the subthalamic nuclei

Block 3 (14 decks)

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