Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Year 2 Term 3 Control > Drug treatment of movement disorders > Flashcards

Drug treatment of movement disorders Flashcards

1
Q

What are the 3 defining characteristics of neurodegenerative disorders?

A

1) Loss of neurons
2) Progressive
3) Irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Does Parkinson’s disease present subtly or suddenly?

A

Present subtly and gets progressively worse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Remission in Parkinsons is very rare, in which 2 situations does temporary remission sometimes occur?

A

1) Fear - in a life threatening situation can temporary overcome symptoms
2) Excitement - May temporarily overcome symptoms when excited
This never lasts for more than a few minutes or seconds though

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How many years from the onset of symptoms to death?

A

10-15 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the usual cause of death in Parkinson’s disease?

A

Bronchopneumonia - not the actual disease that kills you but in the end stages then movement so severely reduced that patient bed bound and has poor lung ventilation so likely to become infected with opportunistic infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 5 main groups of symptoms of Parkinsons disease?

A

1) Tremor - 4-7Hz, pill rolling, can be unilateral
2) Rigidity - due to increased muscle tone, limb stiffness
3) Speech - slurred, monotone, dribbles, dysphagia later - all due to loss of control and increased tone of facial muscles
4) Akinesia - difficulty in initiating movement, facial immobility and blinking reduced (Serpentine stare)
5) Postural changes - stoop, shuffling, poor arm swinging, balance impaired, telegraph pole falls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What characteristic types of falls occur in Parkinson’s and why?

A

Telegraph pole falls - increased tone, cant move easily so fall rigidly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Is the tremor in Parkinson’s always bilateral?

A

No- can be unilateral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 5 components in the pathology of Parkinson’s disease?

A

1) Loss of neurones in substantia nigra
2) Lewy bodies acculmulate
3) DA-ergic neurones affected
4) Loss of nigro-striatal inhibitory/ excitatory pathway
5) Affects midbrain nuclei

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In Parkinson’s you get loss of neurones in what area?

A

Substantia nigra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What kind of neurones are lost in Parkinsons?

A

dopaminergic (DA-ergic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are Lewy bodies?

A

Inclusion bodies found in Parkinsons - found inside the neurones leading to their death. Made up of intracellular proteins - mainly alpha-synuclein - which aggregate and build up in neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

The cause of Parkinson’s disease is unknown, but what 3 conditions are Parkinson’s like disorders?

A

1) Drug-induced (iatrogenic) - eg those that alter DA activity - Reserpine, Phenothiazines, Butyrophenones
2) MPTP induced - recreational amphetamines contaminated with MPTP
3) Post encephalitic Parkinson’s-like syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What pathway is involved in Parkinson’s disease?

A

Via D2 receptors the DA-ergic neurons of the substantia nigra send output to the thalamus via the Striatum. Thalamus sends signals to the motor cortex which then innervate skeletal muscle. There are also inhibitory DA-ergic neurons from the substantia nigra which act on the striatum. Net result is output from thalamus to motor cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the 2 general approached to treatment of Parkinson’s disease?

A

1) Increase DA activity

2) Decrease ACh activity - has an inhibitory effect on DA pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

In what 4 ways can you increase DA activity in Parkinson’s therapy?

A

1) Replace DA (L-DOPA)
2) Decrease DA breakdown (MAO inhibitors, COMT inhibitors)
3) Increase DA release (amantidine)
4) DA agonists (bromocriptine, pergolide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How can you decrease ACh activity in Parkinson’s therapy?

A

Antimuscarinics (Benzhexol, Orphenadrine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Which drug is used to replace DA lost in Parkinsons?

A

L-DOPA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 2 precursors in the formation of DA and which enzymes convert them?

A

Tyrosine - converted by tyrosine hydroxylase to:

L DOPA - converted by DOPA decarboxylase to Dopamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does L DOPA work to increase DA activity?

A

It is the DA precursor and is able to cross the BBB , it enters neurones via carrier mechanism and is converted in neurones and glia, it is retained mainly by neurones and increases DA release from neurones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the main problem with L DOPA?

A

High metabolism in periphery

  • 90% metabolised in intestinal wall by DOPA decarboxylase or monoamine oxidases
  • Of the remaining 10%, 9% is metabolised at other peripheral sights
  • Only 1% reaches the brain - need a massive dose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How is the problem of low bioavailability with L DOPA overcome?

A

Given as combination therapy with Carbidopa which is a DOPA decarboxylase inhibitor which doesn’t cross the BBB and thus increases the bioavailability of L DOPA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the 6 main adverse effects of L DOPA?

A

1) On - off effect - worsening of the Parkinson’s symptoms as the conc of DA drops (worse than before) - mechanism unknown
2) Nausea, vomiting and anorexia (DA receptors in emetic centre in brain)
3) Dyskinesis (increased involuntary movements)
4) Tachycardia, extrasystoles (peripheral, block with domperidone)
5) Hypotension
6) Insomnia , confusion, schizophrenic effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How can the insomnia, confusion and schizophrenic effects of L DOPA be prevented?

A

Block with Clozapine - neuroepileptic effect with no D2 action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How do the side effects of L DOPA change with time and why?

A

Increases with time as greater doses of L DOPA have to be used as neurones die

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Can L DOPA be used in the end stages of Parkinsons?

A

Less useful as the effect wears off as neurons die so there is nothing to convert the L DOPA to DA thus it has no effect of DA activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the mechanism of action of MAO inhibitors in Parkinson’s therapy?

A

Reduce the breakdown of existing DA in the synaptic cleft by inhibiting monoamine oxidases which normally breakdown DA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Give the names of 2 drugs which are MAO inhibitors?

A

1) Selegine

2) Deprenyl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Selegiline is an inhibitor of what kind of MAOs?

A

MAO B selective inhibitor

30
Q

Is Selegline effective alone?

A

Can be effective alone in the early stages, but is ineffective alone in the later stages and is given with L DOPA

31
Q

What are the 2 advantages of Selegline therapy?

A

1) May have neuroprotective effects

2) Few side effects - no cheese reaction

32
Q

What is the advantage of giving Selegline with L DOPA?

A

Reduces the dose of L DOPA necessary

33
Q

What is the one disadvantage of giving Selegline with L DOPA?

A

Potentiates the central side effects of L DOPA

34
Q

Why is Selegline thought to have neuroprotective effects?

A

Anti oxidant and many neurons thought to be killed by oxidative stress

35
Q

What is the mechanism of action of COMT inhibitors?

A

Inhibit the enzyme catacol-o-methyl transferase which breaks down L DOPA and DA thus leading to increased levels of L DOPA and DA

36
Q

Name a drug which is a COMT inhibitor?

A

Entacapone

37
Q

What are the main advantages if COMT inhibitors, when are they useful?

A

Used as an adjunct to L DOPA/Carbidopa therapy

Used in patients with on-off problems

38
Q

What are the 5 main adverse effects of COMT inhibitors?

A

1) Aggravate L DOPA dyskinesias
2) Nausea
3) Diarrhoea
4) Abdo pain
5) Dry mouth

39
Q

What is the mechanism of actions of Amantidine?

A

Increases DA release

40
Q

In which stage of Parkison’s is Amantidine most useful?

A

Early stages

41
Q

What are the side effects of Amantidine, is it recommended?

A

Causes Confusion and hallucinations in the elderly - no longer recommended by NICE in the UK

42
Q

What is the mechanism of action of Bromocriptine and Pergolide?

A

Dopamine agonsits
Bromocriptine - D1/D2
Pergolide - D2 selective

43
Q

Can Bromocriptine and Pergolide be used alone?

A

Can be given alone but often used with L DOPA

44
Q

Why do dopamine agonists need to be taken regularly?

A

Half life of about 6-8 hours
Peak in 1-3 hours
To maintain effect have to take regularly

45
Q

What are the 4 main adverse effects of Bromocriptine and Pergolide?

A

Similar to L DOPA:

1) Dyskinesias
2) Nausea, vomiting
3) Severe hypotensive effects
4) Hallucinations

46
Q

Name 2 anti-muscarinics, used in the treatment of Parkinson’s disease?

A

1) Benzhexol

2) Orphenadrine

47
Q

Anti muscarinics are most effective on which 2 symptoms of Parkinsons?

A

Tremor and drooling

48
Q

Because of the severe central adverse effects of antimuscarinics, in which group of patients are they only used?

A

Young patients with severe tremor

49
Q

What are the 5 severe central adverse effects of anti muscarinics (they don’t really have any peripheral side effects)?

A

1) Confusion
2) Delusions
3) Hallucinations
4) Drowsiness
5) Mood changes

50
Q

What are the possible surgical techniques which could be used to treat Parkinsons, but aren’t used routinely or at all in some cases?

A

1) Lesion removal
2) Implantable stimulators
3) Grafts

51
Q

What are the possible lesions in Parkinsons which may be removed by surgery?

A

1) Motor thalamus - thalamotomy
2) Globus pallidus - Pallidotomy
3) Subthalamus - subthalamotomy

52
Q

How do implantable stimulators work in the treatment of Parkinsons?

A

Stimulator placed into the sub thalamic nucleus to provide direct stimulation of the thalamus

53
Q

What 5 type of grafts may one day be used to treat Parkinsons?

A

1) Adrenal medulla (autologous)
2) Foetal nigral tissue
3) GM fibroblasts (genetically modified to produce DA)
4) Stem cells
5) Xenografts- from pigs

54
Q

What are the 2 main symptoms of Huntington’s?

A

1) Chorea (jerky, involuntary movements)

2) Dementia

55
Q

What age does Huntington’s typically starts?

A

30-50 - juvenile onset most severe

56
Q

How many years between onset of symptoms and death in Huntingtons?

A

10-20

57
Q

How do the 2 sets of symptoms of Huntington’s disease progress?

A

1) Irritability, moodiness and anti social behaviour progresses to full blow dementia
2) Fidgeting and restlessness progresses to gross choreiform movements

58
Q

What are the 2 investigations used to diagnose Hutingtons?

A

1) Genetic testing (polyglutamine repeats)

2) CT/MRI shows cerebellar atrophy

59
Q

What does the CT/MRI of a HD patient show?

A

Cerebellar atrophy

60
Q

What is the pathology of Huntington’s disease?

A

Selective cell loss in cerebral cortex and striatum

First affected are the medium-sized spiny neurones which contain GABA and encephalin

61
Q

What is the inheritance pattern of HD?

A

Autosomal dominant

62
Q

What is the genetic defect in HD?

A

Gene defect on short arm of Chr 4
Locus 4p16.3 codes for Huntingtin
Gives rise to an expanded and repeated CAG repeat

63
Q

How do the levels of neurotransmitters, GABA, Ach, GAD, choline acetyltransferase and DA change?

A 
GABA - decrease
GAD - decrease
ACh - decrease
Choline acetyl transferase - decrease
DA - increase or stay the same
64
Q

Is there a cure for HD?

A

No

65
Q

Can drugs to increase GABA or ACh activity be used in HD?

A

No, they don’t work

66
Q

What 2 drug treatments can be used in HD?

A

1) D2 antagonists - haloperidol and chlorpromazine

2) DA depletion - reserpine and tetrabenzine

67
Q

What are the 2 adverse affects of D2 antagonists used in HD?

A

1) Parkinsonism

2) Restlessness

68
Q

What are the 4 adverse effects of DA depletion used in HD?

A

1) Hypotension
2) Depression
3) Sedation
4) GI disturbances

69
Q

What is a dystonia?

A

A neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures

70
Q

What are the 5 treatments for dystonias?

A

1) DOPA replacement
2) Anticholinergics
3) Benzodiazepines
4) Baclofen
5) Botulinum toxin

Year 2 Term 3 Control (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions