Parkinsons Flashcards
What is the definition of Parkinson’s
A neurodegenerative, progressive disease.
What is PD characterised by
Bradykinesia
Rigidity
Tremor
Postural instability
What percentage of people develop Parkinson’s Disease
At age 60: 1%
At age 80: 4%
What age range does early onset occur and what is it linked to
Ages 21-40
Genetic component links
What is Parkinsonism
A neurological syndrome characterised by tremor, bradykinesia and rigidity
What causes Parkinsonism
-Drugs: Antimycotics, Metoclopramide, TCA and MPTP (Toxin for dopamine neurons)
-Vascular disease
-Trauma
-Parkinson’s plus syndrome
-Multiple system atrophy
-Progressive supranuclear palsy
-Corticobasal degeneration
-Lewy-body dementia
Parkinsonism is not reversible. TRUE or FALSE
FALSE
What is the classic TRIAD that is used to diagnose
BRADYKINESIA / slowness
RIGIDITY / stiffness / increased tone
TREMOR / pill rolling / 4-6 Hz /resting
AND
Postural instability
What are the initial symptoms of Parkinson’s
-Persistent mild fatigue
-Handwriting becomes shaky
-Becoming unbalanced or have difficulty performing sit-to-stand
-Agitation, irritability , depression and anxiety
-Masked face
List the motor symptoms of Parkinson’s
-Hand tremors
-Rigidity/ resistance
-Spontaneous movement become slower
-Imbalance: Vulnerable to falls
- Tiled forward
- Head down
List some non motor symptoms
Depression
Emotional changes
Memory loss
Swallowing difficulties and Lewy bodies -> Dementia
Speech problems
Bladder/Bowel disorders
Excessive sweating
Sleep disturbances
What are Lewy bodies
Insoluble aggregates in neurons
Describe the pathology of PD
1- Degeneration of pigmented neurones in the pars compacta of the substantia nigra.
2- Lewy Bodies
3- Degeneration of brainstem nuclei
What are Lewy bodies composed of
Aggregates containing Alpha-synuclein
In healthy humans what is Alpha-synuclein used for
To control NT release
Describe the neurobiological of the motor system
The Basal ganglia pathway is involved in regulating movement (Extrapyramidal motor system)
GABA cell increased activity due to death of Dopaminergic substantial nigra cells to the striatum
What brain regions are involved in non-motor symptoms and what happens to those regions
Cell death in the:
-Locus coeruleus degeneration
-Nucleus Basalis
-Enteric nervous system NT release
What effect does cell death in the locus coeruleus have on non-motor symptoms
Emotional changed
Anxiety
Stress
What effect does cell death in the Nucleus Basalis have on non-motor symptoms
Memory decline
Cognition decline
What effect does enteric nervous systems NT release degeneration have on non-motor symptoms
Constipation
Swallowing
Drooling
What are the causes PD
Unknown
Genetic (AS)
Environmental factors- toxins such as MPTP
Oxidative stresses - Free radical dopamine are cytotoxic
List the 4 types of pharmacotherapeutic strategies
peripheral dopa decarboxylase inhibitor
to increase the amount that is delivered to the brain
Reduces peripheral side effects
Name 2 dopamine replacement medication and which type of dopa decarboxylase inhibitor that they contain
Co-Beneldopa: Benzerazide
Co-Careldopa: Carbidopa
Side effects of L-DOPA
GI side effect
Cardiovascualr S/E
Postural hypotension
Behavioural
Abnormal involuntary movement (Dyskinesia)
On-Off symptoms
List the some DA receptor modulators
Amantadine
Dopaminergic agonists
Which adjuvant is given along side L-dopa and why
peripheral dopa decarboxylase inhibitor
to increase the amount that is delivered to the brain
Reduces peripheral side effects
What is Amantadine
An Antiviral agent that has anti-parkinsonian activity
What is the mechanism of action of Amantadine
Releases dopamine from intact dopamine terminal in the striatum
List some dopamine receptor agonist (Dopaminergic agonists)
Bromocriptine
Pergolide
Pramipexole
Ropinirole
Apomorphine
Which dopamine agonists bind to D2 receptors
Bromocriptine
Pergolide
Ropinirole
Which dopamine agonists bind to D1 receptors
Pergolide
Which dopamine agonists bind to D3 receptors
Pramipexole
what are the benefits of pergolide
More effective than Bromocriptine so therefore a lowered dose of L-dopa
Cautions associated with Pergolide
Valvular heart disease so is less favourable than newer agents
List the benefits of Pramipexole
Effective as a monotherapy for mild PD
Effective as co-therapy with L-dopa in advanced PD
May reduce affective symptoms of PD
Potential Neuroprotective effect
List the Benefits of Ropinirole
Effective as monotherapy in mild PD
Effective “smoothening” the response to L-dopa
What form is Apomorphine administered
Subcutaneously
What is Apomorphine used for
Advanced cases that are unresponsive to other therapies to refractory motor fluctuation
What types of medication stops the breakdown DA
MAOI -Mono amine oxidase inhibitors
COMT- catechol-o-methyl transferase inhibitors
How many types of MOAs are there and what do they metabolise
2 types
MAO-A: Metabolises NA and 5-HT
MOA-B: Metabolises DA
List the 2 MOAIs used for PD
Selegiline
Rasagiline
What is the mechanism of MAOI for PD
- Binds irreversibly to MA0-B
- Prevents the breakdown of DA and prolongs antiparkinsonian effect of L-dopa
- Lower dose of L-dopa needed
What are the disadvantages of selegiline
Does not have any therapeutic effects
what is the benefit of Rasagiline over Selegiline
Rasagline is more potent
List the name of come COMT inhibitors
- Entacapone
- Tolcapone
What is the mechanism of COMT Inhibitors
Prolong the activity of of L-dopa by preventing peripheral breakdown.
List the antimuscarinic drugs of PD
Benztropine
Orphenadrine
How do anti-muscarinic drugs help with PD
In PD there is an overexcitation of cholinergic neurons
the antimuscarinic drugs will block cholinergic receptor
In which cases are anti-muscarinic drugs used
When the PD is drug induced NOT primary PD
What are some none medical treatments for PD
Brain Graphs
Stem cell therapy
Deep brain stimulation
Why is administering Parkinson’s medication, on time vital
Because the therapeutic window for the drug reduces over time, the dose must be given so that the persons symptoms does not appear.
What adjunct treatments to Levo-dopa
Dopamine agonist: Non ergot then ergot derived
MAO-B inhibitors
COMT inhibitors
Then if the above doesn’t work use Amantadine
When should the dose of Dopamine agonist be reduced
When there are impulse disorders.
