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Block 3 > Basal Ganglia + Pharmacology > Flashcards

Basal Ganglia + Pharmacology Flashcards

(93 cards)

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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
Define chorea
Twitching or jerking a group of muscles
26
Define ballismus
Large, flinging limb movements
27
Define tics
Small involuntary movements
28
Which region is involved in Parkinson's disease? Which neurotransmitter is affected?
Substantia nigra Reduction in dopamine
29
Which region is involved in Huntington's disease? Which neurotransmitter is affected?
Striatum (caudate nucleus + putamen) Reduction in GABA
30
What is the inhibitory neurotransmitter in the basal ganglia?
GABA
31
What is the excitatory neurotransmitter in the basal ganglia?
Glutamate
32
Which area in the basal ganglia is thought to be the 'focal centre' for the generation of tremors?
Globus pallidus
33
Which 2 areas of the brain, in theory, could be removed in order to treat tremors?
Thalamus Globus pallidus
34
Name some motor effects of Parkinson's disease
Bradykinesia Resting tremor Rigidity (lead pipe, cogwheel)
35
Name some other features of Parkinson's (other than motor)
Festinating gait Lack of facial expression Micrographia No weakness Normal reflexes
36
What is the cause of Huntington's disease?
Genetic
37
What motor effects are seen in Huntington's?
Choreiform (jerky, involuntary movement) Clumsy, unsteady gait Difficulty with speech and swallowing
38
Name the 3 main groups of Parkinsonism
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
What are the 4 cardinal symptoms of Parkinson's?
TRAP: Tremor (resting) Rigidity (lead pipe, cogwheel) Akinesia (bradykinesia) Postural instability
40
Name 4 additional symptoms of Parkinson's
Micrographia Mask-like face Sleep disturbances Aprosodia
41
What % of substantia nigra is lost at the time of presentation of Parkinson's disease?
Already 60% loss
42
Name the 4 dopamine pathways
Nigrostriatal Mesolimbic Mesocortical Tubero-hypophyseal
43
Where does the nigrostriatal pathway go from/to?
Substantia nigra to striatum (putamen and caudate nucleus)
44
Where does the tubero-hypophyseal pathway go from/to? What is its role?
Hypothalamus to pituitary To inhibit prolactin
45
Which dopamine pathway is involved in Parkinson's?
Nigrostriatal pathway
46
Where does the mesolimbic pathway go from/to?
Ventral tegmental area to limbic system
47
Where does the mesocortical pathway go from/to?
Ventral tegmental area to prefrontal cortex
48
What are the mesolimbic and mesocortical dopamine pathways involved in?
Emotions Thoughts Higher cortical processes
49
Which dopamine pathways are involved in psychosis?
Mesolimbic Mesocortical
50
What is the main issue in treatment of Parkinson's disease?
Dopamine does not cross the BBB
51
What is the precursor of dopamine?
Levodopa
52
What is the gold standard drug for Parkinson's disease?
Levodopa
53
What needs to be considered when prescribing levodopa?
Nothing more can be done when maximum dose is reached. Levodopa is metabolised quickly
54
Which enzyme breaks down L-dopa in the periphery?
Dopa-decarboxylase
55
Name a dopa-decarboxylase inhibitor
Carbidopa
56
What type of drug is carbidopa
Dopa-decarboxylase inhibitor
57
Which 2 enzymes break down dopamine in the CNS?
Catechol-O-methyltransferase (COMT) Monoamineoxidase (MAOI-B)
58
Give an example of a catechol-O-methyltransferase inhibitor
Entacapone
59
What class of drugs does entacapone belong to?
Catechol-O-methyltransferase (COMT) inhibitor
60
Give an example of a monoamineoxidase (MAOI-B) inhibitor
Selgiline
61
What family of drugs does selegiline belong to?
Monoamineoxidase (MAOI-B) inhibitor
62
When are dopamine agonists used?
Useful in younger patients when you need to prolong treatment Good first line treatment of Parkinson's
63
Give an example of a dopamine agonist
Pramipexole
64
What class of drug is pramipexole?
Dopamine agonist
65
Which dopamine receptor do dopamine agonists primarily work on?
D2 receptors
66
What is a main side effect of dopamine agonists? Which dopamine pathways do they act on to illicit these symptoms?
Psychiatric effects: hallucinations, visions etc. Mesocortical Mesolimbic
67
Name some side effects of dopamine based treatments
Sudden onset sleep On-off effects Drowsiness Psychosis Hypotension Tachycardia Nausea and vomiting
68
What drug is given to fill in the 'on-off' effects of Parkinson's?
Apomorphine
69
Name the common side effect experienced with apomorphine
Nausea and vomitting
70
What drug is given prophylactically before apomorphine use?
Domperidone
71
When are anticholinergics useful in treating Parkinson's?
Iatrogenic (drug-induced) Parkinson's
72
Why are anticholinergics used to treat Parkinson's?
Because a decrease in dopamine leads to an increase in acetylcholine concentration
73
Name an anticholinergic used to treat Parkinson's
Orphenadrine
74
What class of drugs does Orphenadrine belong to?
Anticholinergics
75
What are the 3 forms of Wilson's disease?
Dystonic Pseudoparkinsonism Cerebellar
76
What is Wilson's disease?
Hepatolenticular degeneration caused by copper accumulation
77
What sign might you see in a patient with Wilson's disease?
Kayser-Fleischer rings
78
What is the treatment for Wilson's disease?
Copper chelators Zinc - blocks copper absorption in the gut.
79
Define essential tremor
A familial progressive disorder characterised by intention tremor, not present at rest. Rhythmic tremor 4-12Hz frequency
80
What 2 types of drugs treat essential tremors? Give an example of a drug from each family
Beta- blockers -Propanolol Antiepileptic -Primidone
81
Describe Huntington's disease
Inherited neurodegenerative disorder Autosomal dominant
82
What 4 types of drugs are used to treat Huntington's disease?
Dopamine depleting drugs Antipsychotics Benzodiazepines Antidepressants
83
Give 4 examples of drugs used to treat Huntington's and their drug class
Tetrabenazine -dopamine depleting Risperidone, haloperidol -antipsychotics Diazepam -benzodiazepine SSRIS/TCAs -antidepressants
84
Describe the mechanism of action of tetrabenazine
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
Why does tetrabenazine cause depression?
Because it affects all vesicular monoamine transporters (e.g. 5HT and NA)
86
What 2 diseases are tics seen in?
Wilson's Huntington's
87
What are the 3 treatments for tics?
Patient education 2nd generation antipsychotics 1st generation antipsychotics
88
What are the 2 main treatments for dystonia?
GABA agonists -Baclofen BDZ -diazepam
89
What class of drug is baclofen?
GABA agonist
90
How do you treat chorea?
2nd generation antipsychotics Dopamine depleting drugs (tetrabenazine) GABAergic drugs (anti-epileptics, gabapentin, BDZ)
91
What is athetosis?
Slow, irregular, sinous writhing movements
92
What is ballismus?
large, violent, proximal, flinging movements of the limbs If unilateral = hemiballismus
93
What causes ballismus?
Neurodegeneration of the subthalamic nuclei

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