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