Parkinsons Flashcards
1
Q
Pathophysiology:
A
- Chronic, progressive neurodegenerative disease
- Degeneration of dopaminergic neurones in nigro-striatal pathway
- 50-80% loss before symptoms apparent – damage already done before we see symptoms
- Presence of Lewy bodies in neurons leading to cell death
- Changes in GABA glutamate pathway (increased)
2
Q
Who gets Parkinson’s Disease?
A
- 1 in 500 people in UK
- Average age at onset is 60 years. 5-10% “early onset”
- Men more commonly affected 3:2 ratio
Complex interaction of factors contribute to increased risk
- Genetic factors
- Exposure to neurotoxins
- Head injury
3
Q
Symptoms:
A
Motor symptoms
- Tremor
- Rigidity (stiff)
- Bradykinesia (slowing of movements)
Non-motor symptoms
- Micrographia (large writing to small writing), monotone voice
- Swallowing and speech problems
- Drooling, loss of smell, excessive sweating
- Depression, memory problems and sleep disturbances
- Constipation and urinary problems
- Dizziness and falls
- Dementia
4
Q
Drug treatments principles:
A
- Drug treatments should only be started once motor symptoms affect a patient’s ability to function on a daily basis. E.g. eating, dressing themselves etc
- Drug treatments for motor symptoms aim to increase dopamine levels in the brain, through a variety of mechanisms
- Treatment of symptoms only; not curative or disease modifying - disease progression not affected
- Treatments for non-motor symptoms; symptomatic treatments
5
Q
Drug treatments for motor symptoms:
A
- MAO-B inhibitors
- Dopamine agonists
- Levodopa
- COMT inhibitors
- Amantadine
- Anticholinergics
6
Q
Levodopa:
A
- Levodopa combined with peripheral dopa-decarboxylase inhibitor E.g. Madopar® (co-beneldopa), Sinemet® (co-careldopa), Duodopa®
- DD inhibitors (benserazide, carbidopa) limit peripheral metabolism of levodopa to dopamine; metabolised to dopamine after crossing BBB
- Most effective treatment - relieves motor symptoms of tremor, bradykinesia, rigidity
- Low dose then titrated up to limit side effects of postural hypotension, nausea, vomiting and psychiatric effects
- Initiate when symptoms interfere with daily activities. Until then, use other first line therapies due to long term problems (decreased efficacy and dyskinesias)
7
Q
MAO-B inhibitors:
A
- Selegiline and rasagiline
- Prevent metabolism of dopamine - increase in dopamine at receptors
- Can be used as monotherapy in early PD; better for milder initial symptoms
- Also useful in advanced disease to minimise dose of levodopa
- Rasagiline preferred as selegiline can cause hallucinations and insomnia (amphetamine-like metabolites ) last dose selegiline 1pm to avoid insomnia
8
Q
Dopamine agonists:
A
- non-ergot - ropinirole, pramipexole, rotigotine
- ergot - pergolide, lisuride, bromocriptine, cabergoline
Agonists at post-synaptic dopamine receptors
Useful initial monotherapy - fewer long term problems than levodopa (although less effective for motor symptoms)
- In advanced disease, used with levodopa
- Available mainly as tablets; exceptions are rotigotine (24 hr transdermal patch) and apomorphine (potent – used for more advanced disease) (s/c – covered later)
- Slow initial dose titration needed
9
Q
Dopamine agonists – side effects:
A
ergot: lung and cardiac valve fibrosis
Ergot-derivatives now rarely used
- Nausea and vomiting
- Psychiatric (hallucinations, psychosis)
- Postural hypotension
- Sudden sleep onset
- rarely, Dopamine Dysregulation Syndrome – Craving (gambling, hypersexuality, binge eating) – behavioural changes
more common in young males and if previous history of mental illness
10
Q
Later-stage disease:
A
- As disease progresses, response to treatment declines
- Wearing off
- -> Plasma drug concentrations fall (trough) – patients experience akinesia and rigidity
- On-off
- When drug concentrations peak, patients can experience motor complications (dyskinesia (big rapid movements) and dystonia). On-off is fluctuation between peak and trough drug levels and associated symptoms
- Shorten interval between drug doses or use drug combinations to manage
11
Q
Failure of first-line therapy:
A
- Dopamine agonist or Levodopa monotherapy
- Dopamine agonist and Levodopa combination therapy
- Add Entacapone or rasagiline if unsatisfactory control
Amantadine or antimuscarinic for dyskinesia - Consider apomorphine Duodopa intestinal gel
12
Q
COMT inhibitors:
A
- Catechol-o-methyl transferase inhibitors
- Use in combination with levodopa
- Prevent metabolism of levodopa to 3-O-methyldopa therefore prolong action, can reduce levodopa dose as a result
Entacapone
- Entacapone + levodopa + carbidopa combination product - Stalevo)
–> allows decrease in levodopa dose
Side effects - dyskinesias, nausea, diarrhoea
13
Q
Amantadine:
A
- Glutamate antagonist at NMDA receptor
- Treats dyskinesias in late disease
- Efficacy decreases after several months
Side effects
- psychiatric, e.g. confusion, hallucinations
- GI, e.g. N&V
- oedema, skin rash (livedo reticularis – very apparent tash )
Tachyphylaxis – need more drug to have same effect over time
14
Q
Anticholinergics:
A
- e.g. trihexyphenidyl, orphenadrine
- Now only used for tremor
- Avoid in elderly due to side effects
Side effects
- anticholinergic, e.g. constipation, urinary retention
- psychiatric, e.g. confusion, delusions
- Useful in young, tremor ++
- Do not stop abruptly due to rebound symptoms
15
Q
Duodopa®:
A
- For PD with severe motor fluctuations and dyskinesia
- Intestinal gel
- Administered using pump via PEG tube (invasive)
- Initial trial with NG tube
- Can be used for up to 16 hours/day
