Parkinson's Disease Flashcards
What is Parkinson’s Disease (PD) ?
A progressive neurodegenerative condition – death of dopamine‐containing cells, leading to a deficiency of dopamine.
Symptoms occur when 80% of dopamine is lost
What the clinical features of PD?
Bradykinesia - slowness of movement (if this is not present, then diagonsis cannot be PD)
Extrapyramidal rigidity - lead pipe and/or cog-wheel movements
Resting tremor - ‘pill-rolling’
Postural instability - impairment of righting reflexes and tendency to fall; develops later on
Shuffling gait
Flat affect - reduced blinking and facial expression, monotonous speech; unable to smile and find talking difficult
Loss of arm swing
Micrographia - handwriting small and barely legible
Autonomic dysfunction - urinary urgency and postural hypotension - falls, excessive saliva and sweating
Neuropsychiatric disturbances - psychosis, depression ect.
What must be done before starting treatment for PD?
These must be discussed:
- The person’s individual clinical circumstances, for example, their symptoms, comorbidities and risks from polypharmacy
- The person’s individual lifestyle circumstances, preferences, needs and goals
- The potential benefits and harms of the different drug classes
What is the first line treatment for PD?
For those whose motor symotoms are impacting their Quality of Life - Levodopa
For those whose motor symptoms do not impact their QoL - Dopamine agonists, Levodopa or monoamine oxidase B (MAO-B) inhibitors.
Which medications should not be offered for treatment of PD?
Bromocriptine, pergolide and cabergoline
What medications are used to treat PD?
Levodopa, Dopamine agonists, Monoamine oxidase-B (MAO-B) inhibitors
What is Levodopa?
The precursor to dopamine.
It can cross the blood-brain barrier (BBB) unlike dopamine.
Once crossed, it converts to dopamine in both the CNS and periphery.
How is the bioavailbility of Levodopa increased, with the side effects decreased?
With it being adminstered in combination with peripheral decarboxylase inhibitors.
What do Dopamine decarboxylase inhibitors do?
They prevent the conversion of levodopa to dopamine in the periphery, allowing more levodopa to cross the BBB. Once converted to dopamine, it activates postsynaptic dopaminergic receptors and compensates for the decrease in endogenous dopamine
How can Levodopa absorption be increased? And why?
By patients taking levodopa 1 hour before or 2 hours after meals containing protein.
This is because high protein diets can decrease the amount of levodopa absorbed due to competition with amino acid transporters.
Therefore taking it hours after protein will increase its absorption.
What happens if Levodopa is converted in the periphery?
It can lead to side effects such as nausea and vomiting.
How can GI upset be avoided in patiets with Levodopa?
By taking the oral form of Levodopa with meals and avoiding high fat, high calorie means as it can delay absorption by 2 hours
What is main side effect of Dopamine agonist?
Excessive sleepiness and sudden onset of sleep
What should you do if side effects of Dopamine agonist occurs?
Change to another dopamine agonist or another class of drug
What do Monoamine-oxidase inhibitors do?
Each inhibits monoamine-oxidase B but with some differences e.g., reversibly / irreversibly
MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters e.g., dopamine and thereby increasing their availability
Examples of Dopamine agonists?
Pramipexole, ropinirole
Examples of MAOIS (MAO-B inhibitors)?
Rasagiline, selegiline, safinamide.
Which patients must avoid selegiline?
Avoid in patients with postural hypotension, confusion and falls risk
What is Levodopa treatment assoicated with?
Motor complications, including response fluctuations and dyskinesias
Motor flucations / Response fluctuations?
Response fluctuations are characterised
by large variations in motor performance, with normal
function during the ‘on’ period, and weakness and
restricted mobility during the ‘off’ period. ‘End-of-dose’
deterioration with progressively shorter duration of
benefit can also occur. Modified-release preparations
may help with ‘end-of-dose’ deterioration or nocturnal
immobility.
When are adjuvant treatments given?
If a person with Parkinson’s disease has developed dyskinesia (involuntary movements) and/or motor fluctuations, including medicines ‘wearing off’.
Why does Levodopa dose need to be reduced with adjuvant treatment?
Because adjuvant treatment enhances availability of Levodopa
What medications can be offered as an adjunt treatment to Levodopa?
Dopamine agonists, MAO‑B inhibitors or
catechol‑O‑methyl transferase (COMT) inhibitors
What should be given if dyskinesia does not improve by modifying exisiting therapy?
Amantadine
What should not be given in patients with PD who have developed dyskinesia and/or motor fluctuations?
Anticholinergics
What are the benefits and riks of Dopamine agonist?
- Improves motor symptoms
- Improves in activities of daily living
- More off-time reduction
- Intermediate risk of adverse events
- More risk of hallucinations
What are the benefits and risks of Monoamine oxidase-B (MAO-B) inhibitors?
- Improves motor symptoms
- Improves in activities of daily living
- Off-time reduction
- Fewer risk of adverse events
- Lower risk of hallucinations
What are the benefits and risks of Catechol-O-methyl transferase (COMT) inhibitors?
- Improves motor symptoms
- Improves in activities of daily living
- Off-time reduction
- More adverse events
- Lower risk of hallucinations
What are the benefits and risks of Amantadine?
No evidence of any of these whatsoever
What is COMT inhibitors?
catechol-O-methyltransferase inhibitor
Examples of COMT inhibitors?
Entacapone, Entacapone with levodopa and carbidopa, opicapone and tolcapone
What do COMT inhibitors do?
Inhibits the enzyme catechol-O-methyltransferase.
This enzyme methylates catecholamines e.g. dopamine. It also methylates levodopa, the precursor, to dopamine.
What other medications are COMT inhibitors taken with?
Taken for PD in combination with levodopa and an aromatic L-amino acid decarboxylase inhibitor (e.g. carbidopa or benserazide).
What is the therapeutic effect of COMT ihbitor based on?
It’s ability to prevent the methylation of levodopa to 3-O-methyldopa, thus increasing the bioavailability of levodopa.
What are the cautions for Tolcapone?
Potentially life-threatening hepatotoxicity - cannot be given in those who have abnormal liver function test result or who have liver disorder.
Liver function should be tested before treatment and monitored every 2 weeks for first year, 4 weeks for 6 months and 8 weeks after.
What is Amantadine?
A weak dopamine agonist with modest antiparkinsonian effects.
A Antidyskinetic agent
When is Amantadine given?
When other medications have not been successful / no longer effective
Given as adjunctive therapy and never alone.
What are non-motor symptoms of PD?
Daytime sleepiness and sudden onset of sleep
Nocturnal akinesia
Postural hypotension
Psychotic symptoms
Depression
Rapid eye movement sleep behaviour disorder
Drooling of saliva
Parkinson’s disease dementia
What should be given to treat the non-motor symptoms of PD?
Sleepiness/sudden sleep - Modafinil can be considered to treat symptom with treatment reviewed every 12 months
Nocturnal akinesia - Levodopa or oral dopamine-receptor agonists as first-line options; if one is ineffective, withdrew then traisl other rotigotine as second-line
Postural hypotension - first review current drugs taken as they could be the cause; if not, give midodrine hydrochloride as first option and fludrocortisone acetate as an alternative
Psychotic symptoms - if triggered by any antiparkinsonism drugs, reduce dose; quetiapine can be given to patients with no cognitive impariment; clozapine can be given to patients with PD
Depression -
Rapid eye movement - Clonazepam or Melatonin
Drooling of saliva - Glycopyrronium bromide first-line treatment.
Botulinum toxin type A as second-line.
Other antimuscarinic drugs, should only be considered if the risk of cognitive adverse effects is thought to be minimal
PD dementia - An acetylcholinesterase inhibitor; or rivastigmine
If acetylcholinesterase inhibitors are not tolerated or contra-indicated, memantine hydrochloride should be considered.
** What are the side effects of the treatment for PD?
Nausea and vomiting
Postural hypotension
Neuropsychiatric adverse effects
Impulse control disorders
Insomnia
Constipation
Excessive drowsiness
Diarrhoea
Which medication causes the side effects for PD?
All these side effects can occur when taking Levodopa and when taking dopamine agonists.
Insomnia is caused by all anti-PD drugs.
Constipation can be caused by Levodopa, dopamine agonists and MAO-B inhibitors.
What can cause an increased risk of developing impulse control disorders?
Dopamine agonist therapy
A history of previous impulsive behaviours.
A history of alcohol consumption and/or smoking
Dopaminergic therapies other than dopamine agonists.
How can impluse control disorders be managed?
By modifying dopaminergic therapy by first gradually reducing any dopamine agonist.
And monitoring whether the impulse control disorder improves and whether the person has any symptoms of dopamine agonist withdrawal.
Offer specialist cognitive behavioural therapy targeted at impulse control disorders if modifying dopaminergic therapy is not effective.
What treatment is given to patients with advanced Parkinson’s disease?
They can be offered apomorphine hydrochloride as intermittent injections or continuous subcutaneous infusions. Apomorphine is a strong dopamine agonist and is not related to morphine.
Levodopa-carbidopa intestinal gel is used for the treatment of advanced levodoparesponsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia.
Deep brain stimulation can be used for patients with advanced Parkinson’s disease whose symptoms are not adequately controlled by best drug therapy.
