Parkinsons Flashcards
(18 cards)
how is parkinsons linked with age?
Typical onset in 60s
1 in 20 will be under 40 (early onset)
What is parkinsons diagnosed by (Motor symptoms)?
Cardinal symptoms
- Tremor (Often begins with)
- bradykinesia (slowness of
movement)
- Rigidity
- Postural instability
- 3 of 4 Cardinal symptoms for diagnosis
Classic symptoms
- Micrographia
- Altered posture
- Shuffling gait
What are some other symptoms patients may experience?
Sensory phenomena
- pain
- dysesthesia
sleep disturbances
- sleep fragmentation
- sleep apnea
autonomic nervous system dysfunction
- constipation
- sexual dusfunction
- urinary problems
motor symptoms
- speech abnormalities
- freezing of gait
- postural instability
mental changes
- dementia
- hallucinations
- depression
Pathology of parkinsons
- brains had <10% of normal DA levels in substantia nigra and corpus striatum
- corresponding neuronal loss of the dopaminergic nigrostriatal pathway
- lewy bodies present in CNS and PNS (cytoplasmic protein inclusions mostly contained alpha-synuclein (leads to pathogenic hallmarks in brain biopsies)
What is the role of dopamine?
- Its a neurotransmitter produced in neurons of the substantia nigra
- The nigro-striatal pathway is the main pathway damaged in parkinsons (due to loss of DA producing neurons in substantia nigra)
- nuclei in basal ganglia crucial for the control/initiation of movement
How does the basal ganglia initiate movement?
- Initiate movement
A group of 5 bilateral nuclei
lateral to the thalamus
Caudate
putamen
globus pallidus (interna and
excterna)
subthalamic nucleus
substantia nigra (SN) - Substantia Nigra-excitatory
What is the direct and indirect pathways in the basal ganglia and how does dopamine stimulate movement?
- When dopamine is released from the substantia nigra there are two dopamine receptors D1 and D2
- D1 is mainly for the direct pathway and D2 is mainly for the indirect pathway
- Dopamine enhances the direct pathway where the excitory input to cortex increases
- When dopamine binds to D2 receptors, the excitory input to cortex decreases for the indirect pathway
- The direct pathway enhances movement therefore dopamine stmulates movement
What happens in parkinsons to the indirect and direct pathways?
Due to the decrease of dopamine the indirect pathway increases and the direct pathway decreases leading to less signals going to the cortex that stimulate movement
What are the symptomatic therapies - dopaminergic strategy?
- Replace the dopamine (L dopa)
- Increase the availability of dopamine to brain
- Peripheral AADC inhibitors
- Decrease breakdown of
dopamine
- MAO-B inhibitors
- COMT inhibitors - Replace the post-synaptic
dopamine stimulation
- D2 agonist
What is first line treatment for parkinsons by NICE guidlines
- Ofeer levadopa to people with early stage parkinsons for whose motor symtpoms impact on their quality of life
- Consider a choice of dopamine agonist, levadopa or monoamine oxidase B (MAO-B) inhibitors for early stage of parkinsons for whose motor symptoms do not impact quality of life
What are other symptomatic therapies? (non-dopaminergic)
- For the tremors -
Anticholinergics e.g
Benztropine, mACH antagonist - Weak dopamine agonst - e.g Amantadine - used for L-dopa induced dyskinesia (sort of a side effect from levadopa)
differential diagnosis to parkinsons?
Diseases that exhibit Parkinsonian symptoms but are not idiopathic PD include multiple system atrophy, progressive supranuclear palsy, vascular PD and drug-induced Parkinsonism.
Levadopa therapy for parkinsons disease
- Levodopa + cabidopa or
benserazide to enable
levodopa to cross the BBB and
prevent break down of
levodopa to DA in the gut
(reducing side effects, such as
N&V). - Long-term use of
levodopacan result in the
patient
experiencingdyskinesia
andmotor fluctuations(where
the patient experiences ‘off-
time’ periods, as the drug
wears off and symptoms re-
emerge). - The short half-life and
reducing duration of action
make it important that
patients get their medication
on time every time. - Late and missed doses
contribute to risks of severe
complications (e.g. pneumonia
and falls).
DA agonists for parkinsons
- two subclasses: ergoline and non-ergoline - both target DA D2 receptors
- Ergoline: no longer routinely used due to adverse fibrotic reactions
- non-erogline: remain widely used and include ropinirole and pramipexole.
Name 2 DA agonists and its properties
- Rotigotine is delivered transdermally via a patch, which can be particularly useful where patients have a high tablet burden or where patients have swallowing difficulties.
- Apomorphine is considered in advanced PD.
COMTIs for parkinsons - two examples and when taken
COMTIs prevent peripheral breakdown of levadopa and prolongs its effects.
Therefore levadopa doses need to be reviewed and possibly reduced by up to 30%
e.g entacapone - usually taken with levadopa is available alone and in combination
An alternative is opicapone - taken od
Why are glutamte antagonists taken and give one example
Genrally used to reduce dyskinesia caused by levadopa therapy.
Can be used in all stages of PD but often prescribed when alternative strategy have not effectively managed motor complications
e.g amantadine
Monoamine oxidase B inhibitors (MAO-B inhibitors) - When taken and two examples
They increase the length of DA active in the brain by preventing its break down
e.g Rasagiline and selegiline can be prescribed in early stages of PD as monotherapy or a combination with other treatments in later stages
Concomitant antidepressants are cautioned with MAO-B inhibitors - risk of serotonin syndrome
