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Block 3: Pathophysiology and pharmacology > Pharmacology of the basal ganglia disorders > Flashcards

Pharmacology of the basal ganglia disorders Flashcards

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1
Q

What are the 2 classes of movement disorders?

A

Hyperkinetic

Hypokinetic

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2
Q

What disorders are classed as hyperkinetic?

A 
Hemiballismus 
Huntingdon's Disease 
Dystonias
Wilson's disease (dystonic)
Essential tremor
Chorea
Athetosis
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3
Q

What disorders are classed as hypokinetic?

A 
Parkinson's 
Multiple systems atrophy 
Progressive supranuclear palsy
Wilson's Disease (psuedoparkinsonism) 
Essential tremor
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4
Q

How are movement disorders classified?

A

By activities, assessing rhythm, speed and control

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5
Q

What is dystonia?

A

Twisting and repetitive movements or abnormal postures

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6
Q

What is athetosis?

A

Writhing movements

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7
Q

What is chorea?

A

Twitching or jerking of a group of muscles

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8
Q

What is ballismus?

A

Large, flinging limb movements

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9
Q

What key region is associated with Parkinson’s Disease?

A

Substantia Nigra (degeneration of dopaminergic neurons)

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10
Q

What key region is associated with Huntingdon’s Disease?

A

Striatum (degeneration of GABAergic cells)

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11
Q

What key region is associated with Hemiballismus?

A

Subthalamic Nuclei

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12
Q

What area of the brain is thought to be responsible for generation of tremors?

A

Globus Pallidus

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13
Q

What are the 3 main groups of Parkinsonism?

A

Pure Parkinsonism
Parkinsonism with extras
Pseudoparkinsonism

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14
Q

What is Pure Parkinsonism?

A

Damage to substantia nigra with classic Parkinson’s Disease, including:

Idiopathic (Parkinson’s Disease)
Iatrogenic (induced Parkinson’s e.g. through drug use)
Post-encephalitic

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15
Q

What is Parkinsonism with extras?

A

Classic Parkinson’s Disease plus additional symptoms due to damage to additional sites:

Multiple Systems Atrophy (e.g. classic + ANS symptoms)
Progressive supranuclear palsy (classic + damage to midbrain)

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16
Q

What is Pseudoparkinsonism?

A

Parkinson-like symptoms without degeneration to substantia nigra due to:

Wilson’s Disease
Benign Essential Tremor
Trauma and vascular-related

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17
Q

What are the 4 cardinal symptoms of Parkinson’s Disease?

A

Tremor (resting)
Rigidity (smooth movements that are difficult to do)
Akinesia (bradykinesia)
Postural instability

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18
Q

What additional symptoms can be present in Parkinson’s Disease?

A

Micrographia (small, cramped writing)
Mask-like face (lack of expression)
Sleep disturbances
Aprosodia (change in rhythm, speed etc. of speech)

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19
Q

What dopamine pathway is involved in Parkinson’s Disease?

A

Nigrostriatal (Substantia nigra to Striatum)

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20
Q

What are the treatment principles for Parkinson’s?

A

Don’t start treatment until quality of life is significantly disrupted
Multi-disciplinary (input from SLT, OT, Physio etc.)
Gradual treatment (to avoid reaching maximum doses)

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21
Q

Why can dopamine not be used as a treatment for Parkinson’s and how can this be overcome?

A

Can not cross blood brain barrier

Use of dopamine precursor which can cross BBB (L-Dopa)

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22
Q

What is the problem with using L-Dopa to treat Parkinson’s and how can this be overcome?

A

Levodopa is metabolised quickly (before it gets into the CNS).
Use of dopa-decarboxylase inhibitors (Carbidopa or Benserazide) in combination with L-Dopa

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23
Q

What 2 routes break down Dopamine within the CNS?

Study These Flashcards
A

Catechol-O Methyltransferase

Monoamineoxidase

24
Q

What drugs can be given to prevent breakdown of Dopamine within the CNS?

Study These Flashcards
A

COMT inhibitor - Entacapone or Tolcapone

MAOI-B inhibitor - Selegiline or Rasagiline

25
When would COMT and MAOI-B inhibitors be used?
Can be used as a first line treatment before use of a dopamine agonist or L-Dopa
26
When are Dopamine agonists useful?
Younger patients and initial treatment of Parkinson's
27
What is the main Dopamine agonist?
Pramipexole | Also Rotigotene + Ropinirole
28
What side affects are associated with Dopamine based treatments?
``` Nausea/ vomiting Sudden onset sleeping Anorexia Drowsiness On-off effects Tachycardia/ arrhythmias Psychosis ```
29
What are on-off effects?
On phase - when medication is working well to control symptoms Off phase - when medication has worn off and symptoms much more pronounced
30
How can on-off effects be treated?
Use of Apomorphine to 'fill gaps' during off phases - Domperidone must always be administered prophylactically prior to Apomorphine use
31
What neurological disorder are anticholinergics used to treat?
Iatrogenic (drug-induced) Parkinson's
32
What are the disadvantages of using anticholinergics to treat Iatrogenic Parkinson's?
Only have mild anti-Parkinsonism effects (e.g. reducing tremor) May reduce absorption of Levodopa
33
What anticholinergics are used to treat Iatrogenic Parkinson's?
Orphenadrine Procyclidine Trihexphenidyl
34
What glutamate antagonist can be used to treat Parkinson's?
Amantadine
35
What symptoms does Amantadine help to reduce in Parkinson's?
Tremor Rigidity Bradykinesia
36
What is a Kayser-Fleischer ring?
Build up of copper around the iris of the eye | Indicative of Wilson's Disease
37
What are the 3 forms of Wilson's Disease?
``` Dystonic Pseudoparkinsonism Cerebellar (pseudosclerotic) ```
38
How can Wilson's Disease be treated?
By reducing copper levels using a Copper chelator or Zinc
39
How do Copper Chelators work to reduce copper levels?
Cause excretion of excess copper Used as maintenance after initial excretion of copper Examples: Penicillamine or Trientine
40
How does Zinc work to reduce copper levels?
Blocks absorption of copper in the gut to prevent further build up Fewer side effects than alternative therapeutics
41
What is Essential Tremor?
Familial progressive disorder characterised by intention tremor (not present at rest) Tends to first appear in arms before spreading to rest of body (particularly the head, neck, jaw and voice) Generally bilateral
42
What is titubation?
Head tremor | More common in females
43
What is the treatment for Essential Tremor?
Beta-blocker (Propanolol) Anti-epileptic (Primedone) Botox (Botulinumn toxin type A) - used for head and voice mainly 1-2 units of alcohol (for tremor)
44
What is Huntingdon's Disease?
Inherited neurodegenerative disorder Autosomal dominant Degeneration of GABAergic cells in the striatum (generally starts in caudate nucleus before progressing to putamen) - causes cholinergic dysfunction
45
What is the treatment for Huntingdon's Disease?
Dopamine depleting drugs (Tetrabenazine) - reduces involuntary movements Antipsychotics (Risperidone, Haloperidol) - reduces chorea and tics; controls delusions, hallucinations and violent outbursts Benzodiazepines (Diazepam) Antidepressants
46
What is the MoA for Tetrabenazine?
``` Dopamine depleting drug: Blocks VMAT2 (vesicular monoamine transporter) Prevents transport of Dopamine into vesicles thus preventing release of Dopamine into synaptic cleft ```
47
What is the disadvantage of Tetrabenazine?
Prevents release of all monoamines rather than selectively inhibiting Dopamine release - this causes depression due to decreased levels of 5HT and NA
48
What is a tic?
Small, involuntary movement | Seen in Tourettes, Wilson's Disease and Huntingdon's Disease
49
How can tics be managed?
Patient education (tic management) 2nd gen antipsychotics 1st gen antipsychotics
50
What is dystonia?
Lasting muscle spasms causing repeated twisting movements or altered posture Can be primary (genetic) or secondary (acquired)
51
How is dystonia managed?
``` Botox injections (Botulinum toxin A) Anticholinergics GABA agonist (Baclofen) - antispasm BDZ GABA co-agonist (Diazepam) - muscle relaxant Physiotherapy Deep brain stimulation Denervation ```
52
What is chorea?
Involuntary, irregular, flowing movements | Can be primary (inherited e.g. HD) or secondary (acquired e.g. medication side effect or toxins)
53
What is the treatment for chorea?
2nd gen antipsychotics Dopamine depleting drugs (Tetrabenazine) GABAergic drugs (e.g. antiepileptics, benzodiazepines) Steroids (for post op chorea)
54
What is athetosis?
Slow, irregular, writhing movements - often in fingers Athetosis + Chorea = choreoathetosis Same treatment as for chorea
55
What is ballismus?
Large, violent, proximal, flinging movements Often in limbs Hemiballismus = unilateral
56
What causes ballismus?
Degeneration of subthalamic nuclei | Lesion
57
How is ballismus treated?
Same as chorea (2nd gen antipsychotics, dopamine depleting drugs, GABAergic drugs) IV Diazepam Oral Haloperidol

Block 3: Pathophysiology and pharmacology (16 decks)

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