Parkinsons disease Flashcards
what is parkinsons disease?
Parkinson’s disease is a common and complex neurological disorder, affecting mainly movement
causes by loss of dopaminergic neurones in the substantia nigra.
what are motor symptoms of parkinsons?
Bradykinesia (slowed movement):
Slowness of walking and other movements
Reduced armswing or stride length
Reduced facial reaction (“masked face”
Softer or slurred speech
Smaller handwriting
Muscular rigidity
Stiffness of limb(s)
Sometimes associated with pain
Rest Tremor
Tremor in one limb with the limb at rest
Tremor with holding a posture or with action
asymmetric
Imbalance
Loss of balance reflexes
what are non-motor symptoms?
Autonomic dysfunction:
Orthostatic hypotension
Urogenital dysfunction
Constipation
Heat or cold intolerance
Sleep disorders:
Sleep fragmentation
Insomnia
REM sleep behaviour disorder (RBD)
Sleep attacks
Neuropsychiatric disorders:
Fatigue
Anhedonia
Depression and anxiety
Dementia
Sensory disorders:
Pain
Colourvision deficits
Abnormal sensation
what is the role of dopamine on a patient with parkinsons
Dopamine is critical for control of movement and acts as a neurotransmitter in the substantia nigra
Dopamine effect on synaptic levels?
substantia nigra located in mid brain
dopamine reaches the sub thalamic nucleus , putamen, globus palidus into the thalamus into the cortex
with positive and negative dopamine signals- it will initiate movement .
Action potential occurs at synaptic levels
Vesicles fuse with synaptic membrane
Dopamine is released
Dopamine binds to dop receptor - d1 and d2
Transmitting signals
what are the two key pathological hallmark of parkisons?
Loss of neurons, predominantly dopaminergic and in the Substantia nigra (when pigmented (intracellular inclusion) - up to 70% cell is gone when diagnosed)
The accumulation of intracellular inclusions, called Lewy bodies, made up of the protein alpha synuclein = become toxic = make neurone die
what are the causes of parkinsons disease?
Unknown cause in most cases (idiopathic or sporadic disease)
Specific environmental triggers
Genetic component
environment - pesticides exposure, MPTP exposure - crosses the blood-brain barrier which is toxic for mitochondria, exposure to influenza and repeated head trauma,
How does MPTP effect and its importance?
MPTP exposure - crosses the blood-brain barrier which is toxic for mitochondria
which is essential for energy for the cells - to do functions .
dynamic - fuse together when there is high demand of energy
can be transported to areas of high energy needed areas.
what are the genetic factors?
5 % familiar
95 % sporadic
2 components
- Inherited forms of Parkinson’s disease
- Genetic susceptibility in sporadic Parkinson’s disease
what is an example of a gene which is involved in Parkinsons diease?
PINK1 - mitochondria dysfunction leading to parkinsons
what is the pharmacological treatment of parkinsons disease?
Disease modifying therapies
Existing therapies for PD are exclusively symptomatic
(dopamine)
what are non-pharmacological treatment?
Surgical interventions
what is the dopamine pathway
tyrosine converted to l-dopa which converted into dopamine
Dopamine stored in vesicle
AP cause
Vesicle will fuse
Neurotransmitters will release and bind to receptor
does dopamine or l-dopa move into the blood brain barrier
Dopamine does not cross blood brain barrier
L-dopa can cross blood brain barriers
Dopamine pathway treatments
L-DOPA is ~90% converted by DDC in intestinal wall
- Given with peripherally-acting DDC inhibitors, carbidopa or benserazide
L-DOPA also ~5% metabolised by plasma Catechol O-Methyl Transferase
- COMT inhibitor, entacapone, may be used as adjunct
Ensure majority of L-DOPA enters brain unchanged for conversion to DA
