Treatment of Parkinsons Disease

1
Treatment of Parkinsons Disease

• Thomas L. Davis, M.D.
• Associate Professor of Neurology
• Vanderbilt School of Medicine

2
Treatment of PDQuestion Diagnosis

• Four cardinal features PD (parkinsonism 2/4
  features
• Rest tremor
• Bradykinesia
• Rigidity
• Loss of postural reflexes
• Drug Induced Parkinsonism treatment is to stop
  the offending agent

3
Treatment of PDNeuroprotection

• No proven treatments this is the subject of a
  large NIH trial potential agents under study
  include
• Minocycline
• Creatine
• CoQ10
• GPi- 1485

4
Treatment Of PDGeneral Strategy

• Continuous dopaminergic stimulation may avoid
  long term motor fluctuations
• Small frequent doses
• Longer acting agents (dopamine agonists,
  sustained release prep of L-DOPA)
• Delay metabolism of L-DOPA or dopamine (COMT
  inhibitors, selegiline)

5
Treatment of PDL-DOPA

• Mainstay of therapy single most effect agent
• Increases lifespan in PD pts.
• Many pharmacokinetic challenges
• Now used more sparing than in the past to
  minimize motor fluctuations.

6
Treatment of PD Dopamine agonist

• Longer duration than L-DOPA
• Less effective than L-DOPA
• Less tolerated then L-DOPA
• Frequently used early in disease and as an
  adjunct to L-DOPA

7
Treatment of PDCOMT Inhibition

• Blocks conversion of L-DOPA to inactive
  3-O-methyldopa in the gut
• Prolongs the duration of effect of L-DOPA
• Increases AUC of L-DOPA without effecting Tmax or
  Cmax

8
Treatment of PDOther Agents

• Selegiline specific MAO-B inhibitor prolongs
  the duration of L-DOPA by blocking the metabolism
  of dopamine
• Amantadine many minor actions including
  glutamate antagonist has mild antiparkinsonian
  effect and may block dyskinesia

9
Treatment of PDNon motor symptoms

• Cognitive difficulty
• Depression
• Constipation
• Sexual dysfunction
• Sleep disorders

10
Treatment of PDDrug AEs

• Nausea carbidopa / domperidone
• Nightmares / Hallucinations atypical
  neuroleptic use with caution
• Orthostatic hypotension water, salt,
• Hypersexuality - atypical neuroleptic

11
Treatment of PDDeep Brain Stimulation

• Use to treat PD complicated by severe motor
  fluctuations not responsive to medications.
• In general, it does not improve sx that L-DOPA
  does not.

12
New Therapies for Parkinsons Disease

• Apomorphine rapidly acting, brief duration SQ
  dopamine agonist for unpredictable off periods.
• Rapidly dissolvable L-DOPA