Parkinson's Flashcards
What impact do the main symptoms of Parkinson’s have on the patient?
Postural instability Stooped posture Hard to start/stop movements Speech problems Expressionless face Depression Writing problems Difficulty swallowing
What are the most common symptoms of Parkinson’s disease?
Tremor, shaking
Rigidity - no smooth movements, broken down into smaller jerky parts
Bradykinesia - slowness of movement. Short shuffling steps
What factors can produce Parkinsonian symptoms, and is this the same as Parkinson’s disease?
Having a stroke, certain infections and certain drugs can all induce Parkinsonian symptoms, but this is not the same as Parkinson’s disease. When they cause is removed, the symptoms should clear.
Parkinson’s disease is currently unknown as to what causes it.
How common is Parkinson’s disease and how does it progress with age?
Most common neuro degenerative disease after Alzheimer’s.
It progresses with age, with higher likelihood as age increases.
Slightly higher instances in men than women.
What is happening in Parkinson’s disease?
Progressive loss of dopamine neurons in the substantia nigra which is a small part of the brain involved in motor control. ( located in the basal ganglia).
This means there is a reduction of dopamine in the striatum, which causes the symptoms.
Loss of 70-80% of neurons before symptoms begin to show.
There are some other pathways that are responsible for the lack of symptoms until the disease has progressed so far, that help the brain carry out normal function.
What is the substantia nigra?
Dark matter in the brain located in the basal ganglia.
Contains dopamine neurons.
What is the nigrostriatal pathway?
It controls motor control, and is responsible for 75% of brain dopamine. Released from substantia nigra into the striatum.
Cell bodies are in the substantia, neurons end in the striatum.
Are the dopamine neurons in the substantia nigra the only dopamine neurons?
No, we have other dopamine neurons in other locations that control diffent functions, such as emotional and behavioural control, and endocrine function.
In Parkinson’s it is the substantia nigra dopamine neurons that are preferentially affected in Parkinson’s.
Because of this it is important to realise that by increasing dopamine we can affect the other aras and produce side effects.
How would dopamine usually work in a nonparkinsons patient?
In this pathway dopamine is inhibitory, so it would normally reduce acetycholine which is excitatory.
Because of this the increased acetycholine in Parkinson’s patients there is over activity, which can cause involuntary muscle contractions.
What causes the death of dopamine neurons in Parkinson’s?
There is no simple genetic test as only a small number of cases are thought to be genetic. In the rest of the cases it is not known what the cause is, it is believed that these neurones are particularly sensitive to certain abnormalities, such as: Change in metabolism Problem with mitochondrial activity Calcium signalling Abnormal deposition of protein
What environmental factors can cause Parkinsonian symptoms, and are these reversible?
Drugs - antipsychotics, calcium channel blockers.
Toxins - designed drugs
Pesticides and fungicide
If the neurones are damaged, they cannot be replaced.
How is Parkinson’s disease diagnosed?
Clinical observation
Detailed history
Difficult to diagnose because may diseases have similar symptoms.
Symptoms
What medical tests can be used to help support a diagnosis of Parkinson’s disease?
SPECT and MRI can be used to exclude leisions.
PET not recommended.
Apart from medication, what other support might a Parkinson’s patient need?
Speech therapy Physiotherapy Dietician Specialist nurse Surgery
What is the aim of treatment in Parkinson’s disease?
There is no cure. Medication treats the symptoms, not the cause of neuro degeneration Improve qualify of life Minimise deterioration Have minimal side effects
What are the two ways Parkinson’s patients can be targeted for in terms of medication?
Increase dopaminergic activity
Reduce cholinergic activity.
Both aim to restore the pathway balance in the basal ganglia.
What drugs are avalible for patients who are diagnosed with early Parkinson’s?
Levodopa is a precursor of dopamine, and will be administered with a dopa decarboxylase(DDC) inhibitor.
Dopamine agonists
Mono amine oxidase b (MAO-B) inhibitors, which reduces how much dopamine is broken down.
Anti cholinergic drugs should not be used as 1st line treatment
What is L dopa and why is it used?
It is a precursor to dopamine.
Dopamine cannot cross the blood brain barrier, so giving it as treatment would be ineffective.
What is the dopamine uptake pathway?
Dopamine is a neurotransmitter.
It is manufactured in several steps from tyrosine.
Initially, tyrosine is convert to dopa( or L dopa) by tyrosine hydroxylase.
Ldopa is then decarboxylased by dopa decarboxylase, which yells dopamine.
In certain cells where there is the presence of specific enzymes, this can then be converted to noradrenaline, and then further converted to adrenaline.
What is the degradation pathway for dopamine?
Dopamine is broken down by monoamine oxidase(MAO) into dihydroxyphenylacetic acid(DOPAC)
DOPAC is further broken down into homovanillic(HVA) by catechol-o-methyl-transferase (COMT).
These can also be targets of drug therapy.
Why is it beneficial for diagnosis and treatment to start earlier in Parkinson’s?
Levodopa is taken up by the remaining dopaminergic neurons, and convert to dopamine by neuronal DDC.
This is why it is important for treatment to start as early as possible, as it requires remaining neurones to have an effect.
What happens to oral Ldopa?
Good absorption, 98% in GI tract, but only In the early tract.
Unfortunately lots of DDC and MAO in Gi and liver, so 70-90% metabolised immediately. (Important to note this could also be converted into NA/A side effects )
The remaining Ldopa enters the systemic circulation, where there are more DDC and COMT break down all but 1%.
Only this 1% passes through the BBB
What improvements will be seen with Ldopa treatment alone in Parkinson’s?
Improvement in initiating and stoping movement.
Smooth and faster more controlled movement.
Improved speech
Reduced tremor.
MUST be some neuronal DDC left for improvement to occur or there is no conversion.
What are the side effects of giving Ldopa on its own in Parkinson’s?
Because there is a lot of dopamine released into the systemic circulation there are a lot of serious side effects.
Cardiac arrhythmia
Hypotension
Gi bleeding
