Parkinson's Disease Flashcards
Define Parkinson’s disease.
The progressive degeneration of dopaminergic neurones in the substantia nigra, leading to a deficiency of dopamine (neurotransmitter)
Dopamine deficiency within the basal ganglia leads to a movement disorder characterised by classical parkinsonian motor symptoms
Also associated with numerous non-motor symptoms, some of which precede the motor dysfunction by more than a decade
What are lewy bodies?
Aggregation of abnormally folded proteins
In a misfolded state, α-synuclein becomes insoluble and aggregates to form intracellular inclusions within the cell body (Lewy bodies)
Lewy pathology is not restricted to the brain but can also be found in the spinal cord and peripheral nervous system
Lewy pathology is hypothesised to be a biological marker for neurodegeneration in Parkinson’s diseas
What are the symptoms of Parkinson’s disease?
Motor
* Bradykinesia (slow movement)
* Muscular rigidity
* Rest tremor
* Postural and gait impairment
Non-Motor
* Olfactory dysfunction (changes to smell and swallowing difficulties)
* Cognitive impairment
* Psychiatric symptoms
* Sleep disorders
* Autonomic dysfunction (dizziness, constipation, incontinence, sexual dysfunction)
* Pain
* Fatigue
What symptoms are prevalent for late stage PD?
After 17 years of disease:
* Up to 80% of patients with PD have freezing of gait and falls
* Up to 50% of patients report choking
* Autonomic symptoms, such as urinary incontinence, constipation and symptomatic postural hypotension are common
Dementia is particularly prevalent, occurring in 83% of patients with Parkinson’s disease who have had 20 years disease duration
What are the symptoms of parkinson’s? (motor and non-motor)
MOTOR
Symptom triad – all patients have all three
1) Rest tremor
- Tremor even when body is at rest
- Asymmetrical – usually on one side of the body
2) Rigidity
- Cog-wheel rigidity – unable to move wrist in a circular fashion
3) Bradykinesia
- Slow movement
- Shuffling when walking
NON-MOTOR
- Swallowing and speech problems
- Depression
- Memory problems
- Drooling, loss of smell, excessive sweating
- Constipation and urinary problems
- Micrographia (small handwriting)
- Dizziness and falls
Patients should be reviewed every 6 - 12 months
Tremor-dominant Parkinson’s disease is often associated with a slower rate of progression and less functional disability than non-tremor-dominant Parkinson’s disease.
True or False?
True
What are the risk factors for PD?
PD results from a combination of genetic and environmental factors:
* Age (greatest risk factor. The prevalence and incidence increase nearly exponentially with age and peak after 80 years of age)
* Location(prevalence seems higher in Europe, North America, and South America than other continents)
* Gender (more common in males. Male-to-female ratio being approximately 3:2)
* Ethinicity (In the USA, incidence is highest in people of Hispanic ethnic origin, followed by non-Hispanic Whites, Asians, and Blacks)
* Environmental factors (smoking, alcohol, illicit and medical drugs)
What environmental factors are thought to increase risk of PD?
In decreasing order of strength of association:
* Pesticide exposure
* Prior head injury
* Rural living
* Beta-blocker use
* Agricultural occupation
* Well-water drinking
What environmental factors are thought to decrease risk of PD?
In decreasing order of strength of association:
* Tobacco smoking
* Coffee drinking
* NSAID and calcium channel blocker use
* Alcohol consumption
Also elevated concentrations of serum urate decrease risk
The number of people with Parkinson’s disease is expected to increase by more than 50% by 2030.
True or False?
True
Current prevalence is 145,000 people with PD in the UK
How is Parkinson’s diagnosed?
Diagnosis is based on the presence of parkinsonian motor features (bradykinesia plus rigidity and resting tremor)
- Based on UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria
- There should be no red flags that suggest an alternate cause of parkinsonism
- Review the diagnosis at regular intervals of 6 to 12 months and reconsider it if atypical clinical features develop
For people with family members with a known monogenic form of Parkinson’s disease, genetic testing can assist in diagnosis. However, positive genetic testing in an asymptomatic individual does not provide a definitive diagnosis
There are generally accepted standard pathological diagnostic criteria for Parkinson’s disease.
True or False?
False
Although the gold standard for diagnosis of Parkinson’s disease is the neuropathological assessment, there are no generally accepted standard pathological diagnostic criteria for Parkinson’s diseas
What are red flag symptoms that require referral to a Parkinson’s specialist?
- Fibrotic reactions (SOB, cough, chest pain, abdominal pain) with ergot-derived dopamine agonists (bromocriptine, pergolide and cabergoline)
- Signs of liver disorder with tolcapone, such as N+V, fatigue, abdominal pain, dark urine or pruritis
- Increased falling, especially early in the condition
- Hallucinations/dementia/depression/cognitive decline, especially early on in the condition
Describe the aim of drug therapy for the treatment of Parkinson’s disease.
Drug therapy does not prevent disease progression, it improves most patient’s quality of life
Drug treatment is started once symptoms reach a level where they are causing a significant impact on daily life
- Since none of these drugs have proven to be neuroprotective or disease-modifying, therapy does not need to be started at time of diagnosis for all patients
Aim is to replace dopamine, however it is not treated directly with dopamine as it cannot cross the BBB
Further classify the dopaminergic drugs ropinirole, pramiprexole, apomorphine and rotigotine.
Non-ergot derived dopamine agonists
Give examples of dopaminergic drugs used in the treatment of Parkinson’s disease.
Levodopa, ropinirole, rotigotine, bromocriptine, cabergoline, pergolide, pramipexole.
With which class of anti-Parkinson’s drugs is there a risk of the patient developing impulse control disorders e.g. gambling, hypersexuality, binge eating?
Levodopa and dopamine agonists (including apomorphine)
More common with dopamine agonists
Reduce dose or stop (gradually)
Which drug provides the greatest symptomatic benefit in PD? (i.e. improvement in motor symptoms and activities of daily living)
Levodopa
But long-term use is associated with motor complications (dyskinesia and motor fluctuations)
To delay the onset of these complications, a levodopa-sparing initial therapy with a monoamine oxidase type B inhibitor or dopamine agonist can be considered
How does levodopa work in the treatment of Parkinson’s disease symptoms?
It crosses the BBB and is converted into dopamine by DOPE decarboxylase, replacing the dopamine deficit which leads to the symptoms of Parkinson’s disease.
Levodopa is always combined with peripheral dopa-decarboxylase inhibitors (benserazide and carbidopa)
- Prevents metabolism of levodopa to dopamine until AFTER it has crossed the BBB
Levodopa is associated with what side effects?
Sudden onset of sleep
Impulse control disorders
* Gambling, hypersexuality
* Punding (where patients perform repeated pointless actions such as sorting or disassembling objects)
* Dopamine dysregulation syndrome—the compulsion to overuse dopaminergic drugs
Motor complications
- Response fluctuations (on and off periods)
- Dyskinesias (sudden jerky movements)
Nausea and vomiting
- Take with or just after food
- Give Domperidone
Postural hypotension
- Give midodrine
Urine discolouration (red)
How can off-periods of levodopa be managed?
- Take at specific times of the day to avoid “off” periods (smaller doses more frequently)
- MR preparations to reduce ‘end-of-dose’ deterioration or nocturnal immobility
- Adding adjunct treatment
What course of action should be taken if a patient with Parkinson’s disease, being treated with a dopaminergic drug experiences impulse control disorders?
The drug should be withdrawn or the dose reduced until the symptoms resolve.
Dyskinesias and motor fluctuations (including the wearing off phenomenon and unpredictable on/off fluctuations) occur in about 40% of patients after 5 years of treatment with levodopa.
What increases the risk of experience this?
- Young onset Parkinson’s disease (90% within five years)
- Longer disease duration
- Higher levodopa doses
How do dopamine agonists work?
They stimulate post-synaptic receptors in the striatum that would normally be activated by dopamine
With regards to the excessive daytime sleepiness and sudden onset of sleep associated with the use of dopaminergic drugs used in Parkinson’s disease, what counselling can be given to patients?
- Warn of the risk and of the need to exercise caution when driving or operating machinery
- If experience sedation or sudden onset of sleep should refrain from driving or operating machines until these effects have stopped occurring
Management of excessive daytime sleepiness should focus on the identification of an underlying cause, such as depression or concomitant medication. Patients should be counselled on improving sleep behaviour.
When is the hypotension associated with dopaminergic drugs most likely to occur?
In the first few days of treatment.
What symptoms of dopaminergic drugs, used in the treatment of Parkinson’s disease, may cause issues when a patient is driving or operating machinery?
Excessive daytime sleepiness, sudden onset of sleep, hypotension.
What is the important safety information regarding pergolide, bromocriptine and cabergoline? (ergot derivatives)
Associated with pulmonary, retroperitoneal (abdomen), and pericardial (heart) fibrotic reactions.
- Any disease/disorder of heart valves must be excluded with ECG before treatment
- Monitor for SoB, persistent cough, chest pain, cardiac failure, abdominal pain or tenderness.
- The risk of cardiac fibrosis is higher with cabergoline and pergolide
Impulse control disorders
- Gradually stop or reduce dose
Before commencing treatment with ergot derivative dopaminergic drugs (bromocriptine, cabergoline, pergolide), what monitoring is required?
ECG, erythrocyte sedimentation rate, serum creatinine, chest x-ray.
During the use of ergot derivative dopaminergic drugs (bromocriptine, cabergoline, pergolide), what symptoms are suggestive of fibrotic reactions?
Dyspnoea, persistent cough, chest pain, cardiac failure, abdominal pain or tenderness.
Patient advice for co-beneldopa?
Sudden onset of sleep - caution when driving/operating machinery
Can discolour urine red (levodopa)
Close ophthalmological monitoring is needed when starting levodopa in patients with what condition?
Narrow angle glaucoma
Because of the potential risk of increasing intraocular pressure
Madopar contains which drug?
Co-beneldopa
Potential benefits and harms of medicines used as adjuvants to levodopa for motor symptoms
