Parkinson's Flashcards by Fehintoluwa Bamgbade

What is the definition of Parkinson’s

A neurodegenerative, progressive disease.

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What is characterised by

Bradykinesia
Rigidity
Tremor
Postural instability

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What percentage of people develop Parkinson’s Disease

At age 60: 1%
At age 80: 4%

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What age range does early onset occur and what is it linked to

Ages 21-30

Genetic component links

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What is Parkinsonism

A neurological syndrome characterised by tremor, bradykinesia and rigidity

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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

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Parkinsonism is not reversible. TRUE or FALSE

FALSE

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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

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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

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List the motor symptoms of Parkinson’s

-Hand tremors
-Rigidity/ resistance
-Spontaneous movement become slower
-Imbalance: Vulnerable to falls
- Tiled forward
- Head down

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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

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What are Lewy bodies

Insoluble aggregates in neurons

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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

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What are Lewy bodies composed of

Aggregates containing Alpha-synuclein

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In healthy humans what is Alpha-synuclein used for

To control NT release

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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

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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

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What effect does cell death in the locus coeruleus have on non-motor symptoms

Emotional changed
Anxiety
Stress

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What effect does cell death in the Nucleus Basalis have on non-motor symptoms

Memory decline
Cognition decline

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What effect does enteric nervous systems NT release degeneration have on non-motor symptoms

Constipation
Swallowing
Drooling

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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

1- Dopamine replacement
2- DA receptor activators
3- Prevention of DA breakdowns
4- Antimuscarinic drugs

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

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

Lis the some DA receptor modulators

Amantadine Dopaminergic agonists

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.