4. Movement disorders

Question 1

What is parkinson’s disease

Answer 1

Loss of dopaminergic neurones in the nigrostriatal pathway

Question 2

Parkinson’s disease symptoms

Answer 2

Motor symptoms
tremors
hpokinesia - reduced movement
bradykinesia - slow movement
rigidity
postural instability

MUST INFORM DVLA

Non-motor symptoms
dementia
depression
swallowing
speech and language changes

Question 3

Parkinson’s disease treatment

Answer 3

If symptoms are reducing quality of life:
1st line levodopa

If there are motor complications:
Levodopa AND
* Dopamine-receptor agonist (non ergot)
* MAO-B inhibitor
* COMT inhibitor

if symptoms are NOT reducing quality of life:
1st line:
* levodopa
* Dopamine-receptor agonist (non ergot)
* MAO-B inhibitor

Dopamine-receptor agonist (ergot derived) are not used as they are associated with harsh side effects

Question 4

Dopaminergic drugs commonly cause nausea and vomiting, this is managed by

Answer 4

Domperidone

Question 5

Avoid abrupt withdrawal with dopaminergic drugs, as it is associated with

Answer 5

Neurleptic malignant syndrome
and
acute akinesia

Question 6

Dopaminergic drugs types

Answer 6

Levodopa
* co-beneldopa (with benserazide)
* co-careldopa (with carbidopa)

Dopamine-receptor agonst
* amantidine
* apomorphine
* carbergoline

Ergot derived - bromocriptine
Non-ergot derived - ropinrole, rotigotine

MAO-B inhibitor
* selegiline
* rasagiline

COMT-inhibitor
* entacapone
* tolcapone

Question 7

Levodopa mechanosm of action

Answer 7

Increases dopamine levels

It is always taken with a decarboxylase inhibitor, to prevent levodopa from being converted to dopamine outside the brain

Question 8

Levodopa side effectcs

Answer 8

dopamine is a sympathomimmetic, it is a rewarding neurotransmitter

Impulse control disorders: gambling, hypersexuality

sudden onset of sleep

Motor complications:
dyskinesia, motor fluctuations, end of dose deterioration (therapeutic effects last for relatively shorter time)

Question 9

Levodopa counselling

Answer 9

Should be taken at specific times

Question 10

Dopamine-receptor agonist mechanism of action

Answer 10

Mimic the actions of dopamine

Question 11

Dopamine receptor agonists (non-ergot)side effects

Answer 11

Side effects:

• impulse control disorders: gambling, hypersexuality
• sudden onset of sleep
• psychotic symptoms: hallucinations
• Hypotensive reactions, through dizziness and fainting.
  Caution: driving

Question 12

MAO-B inhibitor mechanism of action

Answer 12

Blocks monoamine oxidase B to prevent the breakdown of dopamine inside the brain

Question 13

MOA-B inhibitors interactions

Answer 13

1. Interacts with drugs that increase blood pressure, increasing the risk of hypertensive crises:
   pseudoephedrine, phenylephrine, oxymetazoline, xylometazoline (OTC decongestants), adrenaline, noradrenaline, amfetamines, methylphenidates, B2-agonists
2. Interacts with drugs that also increase serotonin levels:
   Antidepressants (SSRI’s, TCA, MAOI), amfetamine, lithium, methadone, St John’s wort, 5-HT3 agonist sumatripatin, 5-HT3 receptor antagonist e.g ondansetron

Question 14

COMT inhibitors mechanism of action

Answer 14

Blocks COMT, to prevent the breakdown of peripheral levodopa

Prevents dopamine breakdown

Sympathomimetics also increased

Question 15

COMT-inhibitors side effects

Answer 15

Side effects:
Red-brown urine -Entacapone

Hepatotoxicity - Tolcapone
Patients must report signs of liver toxicity: persistent vomiting, abdominal pain, dark urine, jaundice

Question 16

COMT-inhibitors interactions

Answer 16

COMT-inhibitors increase the levels of dopamine, adrenaline and noradrenalne (sympathomimetics)

COMT-inhibitos increase the likelihood of cardiovascular effects if taken at the same time as the sympathomimetics. dopamine, adrenaline, noradrenaline