Parkinson's Disease

Question 1

What is Parkinson’s Disease (PD) ?

Answer 1

A progressive neurodegenerative condition – death of dopamine‐containing cells, leading to a deficiency of dopamine.
Symptoms occur when 80% of dopamine is lost

Question 2

What the clinical features of PD?

Answer 2

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.

Question 3

What must be done before starting treatment for PD?

Answer 3

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

Question 4

What is the first line treatment for PD?

Answer 4

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.

Question 5

Which medications should not be offered for treatment of PD?

Answer 5

Bromocriptine, pergolide and cabergoline

Question 6

What medications are used to treat PD?

Answer 6

Levodopa, Dopamine agonists, Monoamine oxidase-B (MAO-B) inhibitors

Question 7

What is Levodopa?

Answer 7

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.

Question 8

How is the bioavailbility of Levodopa increased, with the side effects decreased?

Answer 8

With it being adminstered in combination with peripheral decarboxylase inhibitors.

Question 9

What do Dopamine decarboxylase inhibitors do?

Answer 9

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

Question 10

How can Levodopa absorption be increased? And why?

Answer 10

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.

Question 11

What happens if Levodopa is converted in the periphery?

Answer 11

It can lead to side effects such as nausea and vomiting.

Question 12

How can GI upset be avoided in patiets with Levodopa?

Answer 12

By taking the oral form of Levodopa with meals and avoiding high fat, high calorie means as it can delay absorption by 2 hours

Question 13

What is main side effect of Dopamine agonist?

Answer 13

Excessive sleepiness and sudden onset of sleep

Question 14

What should you do if side effects of Dopamine agonist occurs?

Answer 14

Change to another dopamine agonist or another class of drug

Question 15

What do Monoamine-oxidase inhibitors do?

Answer 15

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

Question 16

Examples of Dopamine agonists?

Answer 16

Pramipexole, ropinirole

Question 17

Examples of MAOIS (MAO-B inhibitors)?

Answer 17

Rasagiline, selegiline, safinamide.

Question 18

Which patients must avoid selegiline?

Answer 18

Avoid in patients with postural hypotension, confusion and falls risk

Question 19

What is Levodopa treatment assoicated with?

Answer 19

Motor complications, including response fluctuations and dyskinesias

Question 20

Motor flucations / Response fluctuations?

Answer 20

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.

Question 21

When are adjuvant treatments given?

Answer 21

If a person with Parkinson’s disease has developed dyskinesia (involuntary movements) and/or motor fluctuations, including medicines ‘wearing off’.

Question 22

Why does Levodopa dose need to be reduced with adjuvant treatment?

Answer 22

Because adjuvant treatment enhances availability of Levodopa

Question 23

What medications can be offered as an adjunt treatment to Levodopa?

Answer 23

Dopamine agonists, MAO‑B inhibitors or
catechol‑O‑methyl transferase (COMT) inhibitors

Question 24

What should be given if dyskinesia does not improve by modifying exisiting therapy?

Answer 24

Amantadine

Question 25

What should not be given in patients with PD who have developed dyskinesia and/or motor fluctuations?

Answer 25

Anticholinergics

Question 26

What are the benefits and riks of Dopamine agonist?

Answer 26

- Improves motor symptoms - Improves in activities of daily living - More off-time reduction - Intermediate risk of adverse events - More risk of hallucinations

Question 27

What are the benefits and risks of Monoamine oxidase-B (MAO-B) inhibitors?

Answer 27

- Improves motor symptoms - Improves in activities of daily living - Off-time reduction - Fewer risk of adverse events - Lower risk of hallucinations

Question 28

What are the benefits and risks of Catechol-O-methyl transferase (COMT) inhibitors?

Answer 28

- Improves motor symptoms - Improves in activities of daily living - Off-time reduction - More adverse events - Lower risk of hallucinations

Question 29

What are the benefits and risks of Amantadine?

Answer 29

No evidence of any of these whatsoever

Question 30

What is COMT inhibitors?

Answer 30

catechol-O-methyltransferase inhibitor

Question 31

Examples of COMT inhibitors?

Answer 31

Entacapone, Entacapone with levodopa and carbidopa, opicapone and tolcapone

Question 32

What do COMT inhibitors do?

Answer 32

Inhibits the enzyme catechol-O-methyltransferase. This enzyme methylates catecholamines e.g. dopamine. It also methylates levodopa, the precursor, to dopamine.

Question 33

What other medications are COMT inhibitors taken with?

Answer 33

Taken for PD in combination with levodopa and an aromatic L-amino acid decarboxylase inhibitor (e.g. carbidopa or benserazide).

Question 34

What is the therapeutic effect of COMT ihbitor based on?

Answer 34

It's ability to prevent the methylation of levodopa to 3-O-methyldopa, thus increasing the bioavailability of levodopa.

Question 35

What are the cautions for Tolcapone?

Answer 35

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.

Question 36

What is Amantadine?

Answer 36

A weak dopamine agonist with modest antiparkinsonian effects. A Antidyskinetic agent

Question 37

When is Amantadine given?

Answer 37

When other medications have not been successful / no longer effective Given as adjunctive therapy and never alone.

Question 38

What are non-motor symptoms of PD?

Answer 38

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

Question 39

What should be given to treat the non-motor symptoms of PD?

Answer 39

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.

Question 40

**** What are the side effects of the treatment for PD?

Answer 40

Nausea and vomiting Postural hypotension Neuropsychiatric adverse effects Impulse control disorders Insomnia Constipation Excessive drowsiness Diarrhoea

Question 41

Which medication causes the side effects for PD?

Answer 41

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.

Question 42

What can cause an increased risk of developing impulse control disorders?

Answer 42

Dopamine agonist therapy A history of previous impulsive behaviours. A history of alcohol consumption and/or smoking Dopaminergic therapies other than dopamine agonists.

Question 43

How can impluse control disorders be managed?

Answer 43

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.

Question 44

What treatment is given to patients with advanced Parkinson's disease?

Answer 44

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.