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

Background Very challenging - bespoke - not ‘off the peg’ Side effects pose major problems Before 1970 - anticholinergics/amantadine/stereotactic surgery Since 1970 - L-dopa L-dopa + peripheral DDCI Selegiline ( MAOB-I ) Bromocriptine Other Dopamine Agonists Apomorphine Entacapone ( COMT-I ) Before 1970 - life expectancy c. 12 years - now improved

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

Management of L-dopa Treatment Failures On/Off Chart

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

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

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

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