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Pharmacological Management of Parkinson’s Disease

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

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Pharmacological Management of Parkinson’s Disease

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  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 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

  3. Levodopa 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 FailuresOn/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

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