1. Pharmacological Management of Parkinson’s Disease
Dr EGS Spokes
Consultant Neurologist
Leeds General Infirmary

2. Background Very challenging - bespoke - not ‘off the peg’
Side effects pose major problems
Before anticholinergics/amantadine/stereotactic
surgery
Since L-dopa
L-dopa + peripheral DDCI
Selegiline ( MAOB-I )
Bromocriptine
Other Dopamine Agonists
Apomorphine
Entacapone ( COMT-I )
Before life expectancy c. 12 years - now improved

3. Levodopa Complications L-dopa Dopamine Reuptake
MAOB
L-dopa
DDC
Dopamine
Reuptake
COMT
Best treatment No response ? PD
Complications
c. 10% p.a.
Related to duration/dosage
Dose related motor fluctuations
- wearing off ± dystonia
- peak dose dyskinesia
Random fluctuations
Psychiatric disorder
? L-dopa accelerates cell death

4. Management of L-dopa Treatment Failures On/Off Chart

5. Management of L-dopa Treatment Failures
Dose related
Wearing off ± dystonia
fractionate dose / dispersible
prolong effect with selegiline / entacopone
add dopamine agonist
Peak dose dyskinesia
fractionate dose / reduce if possible
amantadine
Random
as above + ? protein restriction
apomorphine - penject / infusion

6. Dopamine Agonist Monotherapy
Ergot derivatives - Bromocriptine / Pergolide / Cabergoline
Non-ergots Ropinirole / Pramipexole
All associated with a lower incidence of motor fluctuations
+ dyskinesia c.5%
Advantage less clear in >70’s
Use if life expectancy ≥ 5 years
? Neuroprotective -
Ropinirole PET study / Pramipexole SPECT study

7. Psychiatric Complications
Hallucinations - Delusions - Hypersexuality - Confusion
Reduce / withdraw drugs in order :
Anticholinergics
Amantadine
Selegiline ( ? try Zelapar if worse )
Entacapone
Agonist
L-dopa
? atypical neuroleptic - olanzapine / quetiapine / clozapine
? anticholinesterase

8. Non – Motor Problems Myalgia Depression Somnolence Dementia Autonomic
anticholinergic
TCA / SSRI
? nocturnal sleep disturbed
fractionate doses
? modafanil
anticholinesterase
postural hypotension
constipation
bladder disturbance
sweating / flushing