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2.1 T2: Sensory inputs and motor outputs > T2 L7: Parkinsons disease and drug therapy of basal ganglia disorders > Flashcards

T2 L7: Parkinsons disease and drug therapy of basal ganglia disorders Flashcards

1
Q

What is Ballsismus?

A

A high amplitude flailing of the limbs on one side of the body

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2
Q

What is the pathophysiology of Ballismus?

A

A lesion of the subthalamic nucleus. Most common cause is a stroke

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3
Q

What is coprolalia?

A

Swearing as a symptom of tic disorders

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4
Q

What are the common co-morbidities of tic disorders?

A

50% have ADHD
33.5% have OCD
Up to 50% have anxiety

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5
Q

What is Chorea?

A

Jerky, brief, irregular contractions that appear to flow from one muscle to another. The patient will appear fidgety or restless

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6
Q

What is the pathophysiology of Chorea?

A

A problem with the striatum nucleus. This can be caused by Huntington’s disease or drugs like Neuroepiletics that antagonise dopamine

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7
Q

What causes Huntington’s disease?

A

It’s a trinucleotide repeat on chromosome 4 that is autosomal dominant. The longer the repeat sequence, the earlier the disease presents

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8
Q

What are the clinical presentation of Huntington’s disease?

A

Inability to make decisions or multitask because of slowness of thought
Irritability, depression, apathy, anxiety, delusions
Chorea, motor persistence, dystonia, eye movements

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9
Q

What is astryxis?

A

(Liver flap) caused by muscular inhibitions

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10
Q

What is Myoclonus?

A

Brief movements with rapid onset and offset. It’s a symptoms not a disease

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11
Q

What is the pathophysiology of Myoclonus?

A

Unknown. Believed to be an imbalance between excitatory and inhibitory neurotransmitters since it can be treated with antiepileptic drugs

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12
Q

What causes Myclonus?

A

Juvenile Myoclonic Epilepsy, Brain hypoxia, Prion disease

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13
Q

What is Dystonia?

A

An abnormal twisting posture which may be associated with a jerky tremor

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14
Q

What is the pathophysiology of Dystonia?

A

Not understood. PET scans show problems in motor cortex, supplementary motor areas, cerebellum, and basal ganglia.

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15
Q

What causes Dystonia?

A

Stroke, brain injury, encephalitis, Parkinson’s disease, Huntington’s disease

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16
Q

What are the 3 types of tremor occurrence?

A

At rest, postural, and kinetic

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17
Q

Which parts of the body can a tremor affect?

A

Limbs, head, chin, soft palate

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18
Q

What type of tremor is an essential tremor?

A

Predominantly postural

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19
Q

What is the postulated theory of a tremor?

A

That there is increased activity in the cerebellothalamocortical circuit

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20
Q

What are the different types of drugs used to treat hyperkinetic movement disorders like Tics, Chorea, and Ballismus?

A

Dopamine receptor blocking agents, dopamine depleting agents, and atypical anti-psychotics

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21
Q

Haloperidol, Chlorpromazine, Pimozide, and Risperidone are part of which drug type?

A

Dopamine receptor blocking agents

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22
Q

Tetrabenazine and Reserpine are part of which drug type?

A

Dopamine depleting agents

23
Q

Clozapine, Olanzapine, and Aripiprazole and part of which drug type?

A

Atypical anti-psychotics

24
Q

What are the side effects of dopamine blocking agents?

A

Over days-weeks
Oculogyric crisis, Neuroleptic malignant syndrome

Over weeks-months
Drug induced Parkinsonism

Over months/years
Dyskinesis

25
Q

What us Oculogyric crisis?

A

Spasmodic movements of the eyeballs into a fixed position, usually upwards

26
Q

What is Neuroleptic malignant syndrome?

A

A rare, but life-threatening condition characterized by fever, muscular rigidity, altered mental status, and autonomic dysfunction

27
Q

What is Drug induced Parkinsonism?

A

Symptoms include tremor, rigidity, bradykinesia, and gait disturbance (similar to those of Parkinson’s disease)

28
Q

What is Dyskinesis?

A

Involuntary movements like twitches, jerks, twisting or writhing movements. Treated by gradually withdrawing the offending agent

29
Q

What is Akinetic-Rigid Syndrome?

A

Another name for Parkinson’s disease

30
Q

What are the physical symptoms of Parkinson’s disease?

A

Slowness of movement, stiffness, shaking

31
Q

What are some physical signs of Parkinson’s disease?

A
  • Slowness and poverty of movement (Bradykinesia) Eg, loss of facial expression and arm swing
  • Akinesia
  • Rigidity
  • Resting tremor
32
Q

What are some non-physical symptoms of Parkinson’s disease?

A

Depression and anxiety
Dementia: Slow thoughts, mental inflexibility
Autonomic: Postural hypotension, Hypersalivation
Sleep: Restless legs, REM parasomnia
Reduced sense of smell

33
Q

What is the pathophysiology of Parkinson’s disease?

A

Decreased dopamine release from the substantia nigra causing reduced activation of the direct pathway and reduced inhibition of the indirect pathway

34
Q

What is Parkinson’s disease defined as?

A

A neurodegenerative condition, primarily affecting dopaminergic cells of the substantia nigra

35
Q

What is the Histopathological hallmark of Parkinson’s disease?

A

Lewy bodies

36
Q

What are some Neurodegenerative causes of Parkinsonism?

A

Idiopathic Parkinson’s disease (80%), Diffuse Lewy Body disease, Atypical Parkinsonism caused by Multiple system atrophy, Progressive supranuclear Palsy, and Corticobasal degeneration

37
Q

What are some secondary causes of Parkinsonism?

A

Drugs, cerebrovascular disease, Hydrocephalus, Toxicity/metal deposition disorders

38
Q

What are some genetic causes of Parkinsonism?

A

Metabolic issues caused by Wilson’s disease (Copper deposition) or some rare familial causes

39
Q

What is Dopamine broken down into?

A

Homovanillic acid

40
Q

What are 3 early drug therapies for Parkinson’s disease?

A
  • Amantadine (A Glutamate agonist)
  • Anti-Cholinergics like Procyclidine and Benzhexol to help with tremor but they are limited by side-effects like confusion urinary retentions, and dry mouth
  • Mono-amine oxidase inhibitors
41
Q

What are the 4 types of Monoamine oxidase inhibitors and what is each used for?

A

MAO-type A: Serotonin, Adrenaline, Noredrenaline, and Dopamine
MAO-type B: Dopamine
Non-selective MOA-I: for depression but rarely used because it causes problems with metabolising dietry amines
More selective MAO-IB: for Parkinsons disease (Eg. Selegiline, Rasagiline)

42
Q

What is L-dopa usually combined with and why?

A

Combined with Dopa decarboxylase inhibitor to prevent peripheral conversion of dopamine

43
Q

What are the 2 commercial preparations of L-dopa and how do they differ?

A

Madopar which is immediate release and Sinemet which is controlled release. First is used during the day and the other during the night

44
Q

What happens to the therapeutic window of L-dopa as Parkinson’s disease develops?

A

The therapeutic window gets smaller so dosage is harder to control. Too much causes Dyskinesis

45
Q

What are the drugs Entacapone and Tolcapone used for?

A

They reduce peripheral metabolism of L-dopa which increases the duration of action of L-dopa, efficacy of L-dopa

46
Q

What are some side effects of using Entacapone?

A

Makes Dyskinesia worse and causes diarrhoea

47
Q

What are some side effects of using Tolcapone?

A

Makes Dyskinesia worse, causes diarrhoea, and causes liver disease

48
Q

When is duodenal L-dopa infusion used?

A

With advanced Parkinson’s disease when the therapeutic window is advanced. It’s expensive and doesn’t affect disease progression

49
Q

Why are Ergot dopamine agonists no longer used?

A

Because they caused cardiac and pulmonary fibrosis

50
Q

What are the following drugs used for: Pergolide (Ergot), Cabergoline (Ergot), Pramipexole (Non-Ergot), Ropinirole (Non-Ergot), Rotigotine (Patch), Apomorphine (Subcutaneous infusion)?

A

They are dopamine agonists that reduce the frequency of motor complications with Parkinson’s disease but they can cause dopamine dysregulation syndrome

51
Q

What is Dopamine dysregulation syndrome?

A

A dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time

52
Q

What is Apomorphine, how is it administered and what are the pros and cons of using it?

A

It’s a Dopamine agonist given as a subcutaneous infusion.

Pros: Instant effect. It reduces dyskinesia by allowing continuous dopaminergic stimulation. The pulsatile dopaminergic stimulation is though to prime the basal ganglia for motor complication
Cons: Can only be used to specific patients. Causes skin nodules

53
Q

How is deep brain stimulation used to treat Parkinson’s disease?

A

It’s a non-drug way of disrupting abnormally synchronous basal ganglia rhythms. The subthalamic nucleus us targeted in Parkinson’s disease

Disease will still progress

54
Q

What is Apraxia?

A

A neurological disorder characterized by loss of the ability to execute or carry out skilled movements and gestures, despite having the desire and the physical ability to perform them

2.1 T2: Sensory inputs and motor outputs (14 decks)

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