Parkinsons disease 1

Question 1

Neurodegenerative disorders

Answer 1

Loss of neurones, progressive, irreversible

Question 2

PD

Answer 2

‘Shaking palsy’, akinetic-rigid syndrome (loss of movement, increased muscle tone), extrapyramidal disorder

Question 3

Extrapyramidal disorder

Answer 3

Can be drug induced

Question 4

Symptoms

Answer 4

• Tremor (‘pill rolling’, unilateral, 4-7Hz)
• Rigidity (‘lead piping’)
• Speech
• Akinesia
• Posutral changes

Question 5

Changes in speech

Answer 5

Slurred, monotone, dribbles, dysphagia

Question 6

Akinesia

Answer 6

Difficulty in initiating movement, facial immobility, serpentine stare

Question 7

Postural changes

Answer 7

Stoop, shuffling, poor arm swinging, balance impaired, telegraph pole falls

Question 8

Pathology

Answer 8

• Loss of neurones in substantia nigra
• Lewy bodies (spherical, eosinophilic, contain cellular proteins)
• DA-ergic neurones affected (neuromelanin)
• Loss of nigro-striatal inhibitory/excitatory pathway
• Midbrain nuclei

Question 9

Causes

Answer 9

• Unknown
• Sporadic
• Drug-induced
• MPTP-induced (amphetamines)
• Post-encephalitic

Question 10

Treatment - increase dopamine

Answer 10

• Replace DA (L-DOPA)
• Decrease DA breakdown (MAO/COMT inhibitors)
• Increase DA release (amantidine)
• DA agonists (bromocriptine, pergolide)

Question 11

Treatment - decrease ACh activity

Answer 11

Antimuscarinics (behzhexol, orphenadrine)

Question 12

L-DOPA

Answer 12

DA precursor, crosses BBB, enters neurones via DA uptake transporter > DA (in neurones and glia) retained mainly be neurones, increased DA release from remaining neurones

Question 13

L-DOPA problems

Answer 13

Metabolism in periphery 1% reaches brain, given with cabidopa (doesn’t pass BBB, inhibits DOPA decarboxylase)

Question 14

L-DOPA adverse effects

Answer 14

‘On-off effect’, nausea, vomiting, anorexia, dyskinesias, tachycardia, extrasystoles (domperidone), hypotension, insomnia, confusion, schizophrenic effect (clozapine)

Question 15

Selegiline/deprenyl

Answer 15

MAOb selective inhibitor, prevents breakdown of dopamine, will improve motor symptoms of disorder, neuroprotective, ineffective alone in later stages - prolong L-DOPA

Question 16

COMT inhibitors

Answer 16

Prevent breakdown DA, used for on-off problems

Question 17

COMT inhibitors adverse effects

Answer 17

Aggravate L-DOPA dyskinesias, nausea, diarrhoea, abdo pain, dry mouth

Question 18

Amantidine

Answer 18

Increase DA release

Question 19

Amantidine useful for

Answer 19

Early - mid

Question 20

Amantidine adverse effects

Answer 20

Confusion and hallucination in elderly (usually well tolerated)

Question 21

Dopamine agonists

Answer 21

Bromochriptine (D1/D2) or Pergolide (D2), 6-8hr 1/2 life, 1-3 hr peak taken regularly

Question 22

Bromochriptine (D1/D2) or Pergolide (D2) adverse effects

Answer 22

Dyskinesias, nausea, vomiting, severe hypotension, hallucinations

Question 23

Antimuscarinics

Answer 23

Block ACh receptor in striatum

Question 24

Examples of Antimuscarinics

Answer 24

Benzhexol/orphenadrine

Question 25

Antimuscarinics useful for

Answer 25

Young with severe tremor (drool)

Question 26

Antimuscarinics adverse effects

Answer 26

- Periperhal anticholinergic | - Central (confusion, delusions, hallucinations, drowsiness, mood changes)

Question 27

Surgery of lesions

Answer 27

Thalamotomy (motor thalamus), pallidotomy (globus pallidus), subthalamotomy (subthalamus)

Question 28

Surgery - grafts

Answer 28

Adrenal medulla, foetal nigral tissue (not ethical), GM fibroblasts, stem cells, xenografts (substania nigra pigs)

Question 29

Huntington's disease

Answer 29

Gradual onset, progressive, chorea and dementia, starts 30-50 (juvenile onset more severe), death 10-20 years, cerebellar atrophy

Question 30

Huntington's symptoms

Answer 30

Irritability, moodiness, antisocial behaviour (dementia), fidgeting, restlessness (Gross choreiform movements)

Question 31

Huntington's disease pathology

Answer 31

Selective cell loss in cerebral cortex and corpus striatum (first medium-sized spiny neurones contain GABA and enkephalin)

Question 32

Huntington's disease pathology - neurotransmitters

Answer 32

Decrease in GABA, GAD, ACh, choline acetyltransferase, DA stays same or increases

Question 33

Huntington's disease cause

Answer 33

AD CAG repeat, 4p16.3 (short arm), codes for 'Huntingtin' protein

Question 34

Huntington's disease treatment

Answer 34

Can only control movement - D2 antagonists (haloperidol, chlorpromazine) - DA depletion (reserpine, tetrabenzine)

Question 35

D2 antagonist adverse effect

Answer 35

Parkinsonism, restlessness

Question 36

DA depletion adverse effect

Answer 36

Hypotension, depression, sedation, GI disturbances

Question 37

Dystonia treatment

Answer 37

DOPA replacement, anticholinergics, benzodiazepines (GABA increasing), Baclofen (GABAb receptor agonist), Botulinum toxin (effect motor ouput)

Question 38

Dystonia

Answer 38

Sustained muscle contractions, causing twisting and repetitive movements or abnormal postures