Parkinsons disease 1 Flashcards
Neurodegenerative disorders
Loss of neurones, progressive, irreversible
PD
‘Shaking palsy’, akinetic-rigid syndrome (loss of movement, increased muscle tone), extrapyramidal disorder
Extrapyramidal disorder
Can be drug induced
Symptoms
- Tremor (‘pill rolling’, unilateral, 4-7Hz)
- Rigidity (‘lead piping’)
- Speech
- Akinesia
- Posutral changes
Changes in speech
Slurred, monotone, dribbles, dysphagia
Akinesia
Difficulty in initiating movement, facial immobility, serpentine stare
Postural changes
Stoop, shuffling, poor arm swinging, balance impaired, telegraph pole falls
Pathology
- 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
Causes
- Unknown
- Sporadic
- Drug-induced
- MPTP-induced (amphetamines)
- Post-encephalitic
Treatment - increase dopamine
- Replace DA (L-DOPA)
- Decrease DA breakdown (MAO/COMT inhibitors)
- Increase DA release (amantidine)
- DA agonists (bromocriptine, pergolide)
Treatment - decrease ACh activity
Antimuscarinics (behzhexol, orphenadrine)
L-DOPA
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
L-DOPA problems
Metabolism in periphery 1% reaches brain, given with cabidopa (doesn’t pass BBB, inhibits DOPA decarboxylase)
L-DOPA adverse effects
‘On-off effect’, nausea, vomiting, anorexia, dyskinesias, tachycardia, extrasystoles (domperidone), hypotension, insomnia, confusion, schizophrenic effect (clozapine)
Selegiline/deprenyl
MAOb selective inhibitor, prevents breakdown of dopamine, will improve motor symptoms of disorder, neuroprotective, ineffective alone in later stages - prolong L-DOPA
COMT inhibitors
Prevent breakdown DA, used for on-off problems
COMT inhibitors adverse effects
Aggravate L-DOPA dyskinesias, nausea, diarrhoea, abdo pain, dry mouth
Amantidine
Increase DA release
Amantidine useful for
Early - mid
Amantidine adverse effects
Confusion and hallucination in elderly (usually well tolerated)
Dopamine agonists
Bromochriptine (D1/D2) or Pergolide (D2), 6-8hr 1/2 life, 1-3 hr peak taken regularly
Bromochriptine (D1/D2) or Pergolide (D2) adverse effects
Dyskinesias, nausea, vomiting, severe hypotension, hallucinations
Antimuscarinics
Block ACh receptor in striatum
Examples of Antimuscarinics
Benzhexol/orphenadrine
Antimuscarinics useful for
Young with severe tremor (drool)
Antimuscarinics adverse effects
- Periperhal anticholinergic
- Central (confusion, delusions, hallucinations, drowsiness, mood changes)
Surgery of lesions
Thalamotomy (motor thalamus), pallidotomy (globus pallidus), subthalamotomy (subthalamus)
Surgery - grafts
Adrenal medulla, foetal nigral tissue (not ethical), GM fibroblasts, stem cells, xenografts (substania nigra pigs)
Huntington’s disease
Gradual onset, progressive, chorea and dementia, starts 30-50 (juvenile onset more severe), death 10-20 years, cerebellar atrophy
Huntington’s symptoms
Irritability, moodiness, antisocial behaviour (dementia), fidgeting, restlessness (Gross choreiform movements)
Huntington’s disease pathology
Selective cell loss in cerebral cortex and corpus striatum (first medium-sized spiny neurones contain GABA and enkephalin)
Huntington’s disease pathology - neurotransmitters
Decrease in GABA, GAD, ACh, choline acetyltransferase, DA stays same or increases
Huntington’s disease cause
AD CAG repeat, 4p16.3 (short arm), codes for ‘Huntingtin’ protein
Huntington’s disease treatment
Can only control movement
- D2 antagonists (haloperidol, chlorpromazine)
- DA depletion (reserpine, tetrabenzine)
D2 antagonist adverse effect
Parkinsonism, restlessness
DA depletion adverse effect
Hypotension, depression, sedation, GI disturbances
Dystonia treatment
DOPA replacement, anticholinergics, benzodiazepines (GABA increasing), Baclofen (GABAb receptor agonist), Botulinum toxin (effect motor ouput)
Dystonia
Sustained muscle contractions, causing twisting and repetitive movements or abnormal postures
