Movement Disorders Flashcards

1
Q

What are the 4 dopamine pathways in the brain?

A

Mesolimbic
Mesocortical
Nigrostriatal
Tubero-hypophyseal

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2
Q

What are the 4 cardinal symptoms of PD?

A

Resting tremor
Rigidity (cogwheel/lead pipe)
Akinesia (hypokinesia, bradykinesia)
Postural instability

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3
Q

What are additional features of PD?

A

Micrographia
Aprosodia
Mask-like face
Sleep disturbances

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4
Q

What are some non-pharmacological approaches to treating PD?

A

Physiotherapy
Speech
Occupational therapy
Dietary consultations

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5
Q

What’s the principles of pharmacological treatment of PD?

A

Need to increase DA levels
Not treated until symptoms are severe
Dose titrated gradually against symptoms

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6
Q

What’s the precursor of DA that does cross the BBB?

A

L-Dopa -> Dopamine by dopa-decarboxylase

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7
Q

What’s the problem with using L-Dopa?

A

Becomes ineffective after the maximal dose is reached and it’s metabolised quickly

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8
Q

What can you do to prevent breakdown of L-Dopa?

A

Dopa-decarboxylase inhibitors: Carbidopa to slow down metabolism

Inhibit COMT (Entacapone) and MAOI-B (Selegiline) to prevent breakdown in CNS

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9
Q

How is dopamine broken down?

A

By two routes:

By catechol-o-methyltransferase or by monoamine oxidase B

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10
Q

What are synthetic DA agonists?

A

Replace lost DA acting on D2 receptors
Useful in initial treatment and younger patients

Pramiprexole
Rotigotine
Ropinirole

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11
Q

What are some side effects of DA based treatments?

A
Sudden onset sleep
Nausea and vomitting
Anorexia
Drowsiness
Psychosis
Hypotension
Tachycardia
Arrhythmias
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12
Q

What are on-off effects?

A

Major side effect of long term DA treatment (>2 years)
Duodopa (implanted gel of L-dopa and Carbidopa) useful for treating
Domperidone + Apomorphine can be used to ‘fill in the gaps’

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13
Q

How can anticholinergics be used in PD?

A

Decrease in DA leads to increase in ACh
Anticholinergics good for iatrogenic (drug induced) PD

Eg Orphenadrine

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14
Q

How does Amantadine work and what can it be good for?

A

In Parkinsonism treatment of tremor, rigidity and bradykinesia
It’s an NMDA antagonist and weak DA agonist (may reduce dyskinesias)

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15
Q

What are the 3 main groups of PD?

A

Pure Parkinsonism - idiopathic, iatrogenic, post encephalitic

Parkinsonism with extras - multiple systems atrophy, progressive supranucelar palsy

Pseudoparkinsonism - benign essential tremor, Wilson’s disease, trauma and vascular-related

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16
Q

What’s Wilson’s disease?

A

Hepatolenticular degeneration caused by copper accumulation
Treatment = reduce copper levels by using copper chelators or zinc

3 forms: dystonic, pseudoparkinsonism, cerebellar

17
Q

What’s essential tremor and its treatments? How is it different to the tremor seen in pure PD?

A

Familial progressive tremor characterised by intention tremor - PD has resting tremor whereas intention tremor isn’t present at rest

Tremor first appears in arms then spreads to other areas

Propranolol
Primidone (AED)
18
Q

Which neurones and where degenerate in HD?

A

GABAergic cells in the Striatum (particularly caudate nucleus)
And Cholinergic dysfunction

19
Q

What type of disorder in HD?

A

Autosomal dominant

20
Q

What are the treatments for HD?

A

Symptomatic:
DA depleting drugs: Tetrabenazine to reduce involuntary movement
Antipsychotics: Risperidone, Haloperidol to reduce chorea, tics, hallucinations
Benzodiazepines: Diazepam to aid relaxation
Antidepressants

21
Q

How does Tetrabenazine work?

A
DA depleting drug
VMAT2 blocker (vesicular monoamine transporter) = prevents DA transport into vesicles therefore less is released in the cleft

But it affects all monoamines not just DA

22
Q

What are tics?

A

Small involuntary movement - treated with antipsychotics

23
Q

What’s dystonia and its treatments?

A

Lasting muscle spasms causing repeated twisting movements or altered posture

Baclofen (GABA agonist)
Diazpeam (BDZ, GABA-A co-agonist)

24
Q

What’s chorea and its treatments?

A

Involuntary irregular random dance-like movements from one part of the body to another

2nd generation antipsychotics (DA antagonists)
DA depleting drugs: Tetrabenazine
GABAergic drugs (AEDs Gabapentin and BDZs)

25
Q

What’s athetosis?

A

Slow irregular writhing movements of the fingers

26
Q

What’s choreoathetosis?

A

When chorea and athetosis occur together

27
Q

What’s Ballismus? Which nuclei are affected?

A

Large violent flinging movement of the limbs (hemiballismus is unilateral)

Neurodegeneration of sub thalamic nuclei in basal ganglia
Treated same as chorea: sometimes IV Diazepam and oral Haloperidol

28
Q

Which classes of drug can be used to treat hypokinetic and hyperkinetic disorders?

A

Hypokinetic: Dopamine agonists and Anticholinergics

Hyperkinetic: Dopamine antagonists, Antipsychotics and DA-depleting drugs