Parkinsons Flashcards
What is the underlying pathophysiology of PD
Neurodegeneration of the extra pyramidal system and loss of striata like dopamine
What neurotransmitters cause what in PD
Loss of dopamine in the striatum causes motor problems
Loss of neuropeptides in the striatum also causes motor problems
Loss of NA and Ach in the Cortex- dementia
Loss of dopamine in Mesolimbic areas- psychiatric problems
Loss of hypothalamic amines -endocrine changes
What can people with Parkinson’s do in terms of a motor plan
Can assemble motor plan (select from memory or assemble new sequence) but they are unable to specify accuracy of the programme and run/sequence them
How can Parkinson’s be imaged
PET or SPECT Scan
Visualises and quantifies dopaminergic neuroma using radioactive ligands which bind to dopamine transporter proteins
What is the cause of neuronal cell death in PD
Lewy bodies- eosinophilic inclusions with a core of alpha-synuclein aggregates form fibrils (dementia) in substantia nigra and locus coruleus
What causes cell death in PD
Oxidative stress
Mitochondrial dysfunction
Proteosome dysfunction
What drug treatments in terms of action are available for PD
Dopamine replacement Dopamine agonists Dopamine metabolism blockers Increase dopamine release Indirect dopamine enhancement
What is the first line treatment for PD
L-DOPA + carbidopa
What are alone side effects of L-DOPA
Choreic movements Rapid fluctuations in clinical state Nausea and anorexia Hypotension Psychiatric effects
Name a dopamine agonist and how it works
Ropinirole Full D2 (3>2>4) agonist, inhibits the inhibitory pathway of movement
What is Selegiline
Monoamine oxidase inhibitor
May also protect against neurodegeneration
How can DA release be enhanced
Amantidine, increases release and blocks reuptake
How can DA release be indirectly enhanced
Adenosine A2a receptor antagonist
Briefly describe the direct pathway of movement
Pro movement
Activation of striatal excitatory Medium spiny neurons expressing substance P from cortex
Increase strationigral GABA transmission
Decrease nigrothalamic GABA transmission
Increase thalamocortical glutamate transmission
Briefly describe the indirect pathway of movement
Anti-movement
activation of medium spiny neurons expressing ENK from cortex
Increases straitopallidial GABA transmission
Decreases tonic inhibition on the subthalamic nucleus
Increased glutamate transmission to globus pallidus interna/ substantia nigra pars reticularis
Increased palliothalamic/nigrothalamic GABA tranmission
Decreased thalamocortical glutamate transmission
What are the genetic causes of PD
Park1 gene codes for alpha-synulcein, autosomal dominant, early onset PD with Lewy bodies and marked rigidity
Park2 gene codes for Parkin- part of ubiquitin proteasomes- autosomal recessive early onset with no Lewy bodies and good Levodopa response
LRRK2 gene- sporadic PD
What are some non-genetic causes of PD
Drug induced neurodegeneration
Viral encephalitis
What at the symptoms of Parkinson’s disease
Early- resting tremor Rigid posture/postural abnormalities Mask like facial expression Akinesia Poor slow movements Late- depression dementia and endocrine dysfunction
