Parkinson's Flashcards
What is the difference between Neurodegenerative and psychiatric diseases?
Neurodegenerative:
* Apoptosis/loss of neurons
* Disrupted/loss of (motor) function
* May also inlude changes in behaviour
Psychiatric:
* No obvious loss of neurones though may show some structural damage
* Developmental defects
* Change in behaviour
What are types of movement disorders?
- Upper Motor Neuron Disorders (Cranium or spinal cord)
* Stroke
* MS
* Amyotrophic lateral sclerosis (ALS) - Lower Motor Neuron disorders (Outside brain, muscle innervating neurons)
* Peripheral nuropathy
* Myasthenia Gravis
* Immune disease against nicotinic receptors - Involuntary Movement Disorders (Basal ganglia)
* Parkinson’s disease
* Huntington’s disease
* Tremor - Cerebellar disorders
* Various tumour
What is Parkinson’s disease?
Neurodegeneration of the extrapyrimidal system.
What does Parkinson’s degeneration lead to?
- Unable to perform normal motor function OR initiate movement
1. Poor slow movt
2. Postural abnormality
3. Rigid posture
4. Mask-like expression
5. Lack or rigidity of movt
6. Tremor - Later stages also include:
1. Depression
2. Dementia
3. Endocrine function - Main Neurochemical effect:
1. Loss of striatal dopamine
What is the function of the Basal ganglia?
- Programming of movement (How, when and where to act)
1. Stimulus to move
2. Assemblemotor plan
3. a) Select motor programme from memory stores
b) Assemble appropriate sequence of motor programmes
- Execute motor plan
PD-unable to specify accuracy of programmes, run or sequence them
What dopamine pathways are effected in Parkinson’s?
- Nigrostriatal pathway
What is the primary pathology of Parkinson’s?
Loss of pigmented neurons in substantia nigra pars compacta
What NTs are involved in Parkinson’s?
- Dopamine in striatum ↓ (loss of 60-70% = symptoms)
- Also loss of dopamine in mesolimbic areas (mood changes)
- Hypothalamic amines ↓
- Cortical noradrenaline and ACh ↓ (cognitive loss)
- Neuropeptides (spinal neurons, interneurons) in striatum↓ (substance P, Enkephalins)
Motor Impairment - 1+5
Psychiatric - 2+4
Endocrine - 3
How do you diagnose using visual techniques?
- Diagnosis by visualises dopaminergic neurons using radio-ligand which binds to presynaptic DAT
What are the charachteristic features of Neuronal cell death?
- Lewy Bodies – Inclusions in neurons with core of a-synuclein (aggregate form fibrils and may cont to dementia (50% parkinson’s patients)
- Caused by mutations and hyper-phosphrylation
- Substantia nigra, locus coeruleus
- LB are not unique to PD, Alheimer’s
- Causal or symptomatic
What is cell death due to?
Possibly due to:
* Genetic
* Oxidative stress
* Mitochondrial dysfunction
* Proteasome dysfunction
OR combo.
What are Drug treatment options for PD?
- Drugs that enhance Dopamine levels (D2 receptors remain)
- Dopamine– BUT Does not cross BBB X
- L-DOPA crosses BBB BUT pripheral dopamine production ^ (e.g. kidneys) X
- L-DOPA with peripheral DOPA decarboxylase inhibitor-Carbidopa ✓
What are unwanted side-effects of long term use if L-DOPA?
- Dev of choreic movts~2 years
- Rapid fluctuation in clinical states ‘on-off effect’
- Nausea and anorexia–peripheral effect
- Hypotension–Not a major problem
- Psychotic effects–Mesocortical pathways
How do Dopamine agonists work?
- Target different targets
- Post-synaptic DA receptors not altered by PD
- D2 receptors are inhibitory–main ones in Basal Ganglia, coupled to Gai
- D1 receptors are excitatory–Few in basal ganglia, coupled to Gas
- Use D2 receptor agonist to treat the symptoms especially in early onset, young patients
What is Ropinirole?
- Acts on D2,3,4 receptors
What drugs prevent dopamine metabolism?
- Reuptake: DAT inhibitors (DAT degenerates in PD) – Not used
- Monoamine oxidase: MAO-B inhibitors – Selegiline
- Catechol-O-Methyl transferase: COMT inhibitors
