THE PHARMACOLOGICAL TREATMENT OF PARKINSONS DISEASE

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THE PHARMACOLOGICAL TREATMENT OF PARKINSONS
DISEASE

• Dr. Kay Double
• PRINCE OF WALES MEDICAL RESEARCH INSTITUTE
• www.powmri.edu.au/staff/double.htm

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Parkinsons disease

• Progressive movement disorder of (usually)
  unknown cause
• Estimated 80,000 cases in Australia
• Incidence increases with age (but 1 in 10 are
  under 40 yrs old)
• Average age of onset 62 years, duration 20 years
• Characterised clinically by tremor at rest,
  rigidity, bradykinesia
• Symptoms typically are unilateral and proceed to
  affect both sides of the body
• Non-motor symptoms include autonomic system
  dysfunctions, depression and a diminished sense
  of smell

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PD pathology
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The normal motor circuit
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The motor circuit in PD
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The healthy dopamine neuron
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L-Dopa the Gold Standard
Madopar Sinemet
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L-dopa in the brain
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Adjunct treatments to L-dopa
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Dopamine agonists
Pergolide Bromocriptine Cabergoline Ropinirole Pra
mipexole Apomorphine
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Anticholinergics
Benzhexol Benztropine Orphenadrine Biperiden Pro
cyclidine
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Choice of Treatment

• Treatment type and timing is dependent upon
• The patients symptoms (type, severity)
• The patients need for motor control and his/her
  attitude towards the symptoms
• The treating physicians beliefs on treatment
  efficacy and timing

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Treatment issues

• Long-term/high dose L-dopa treatment can cause
  further abnormal movements to develop
  (dyskinesias)
• As the disease progresses the period of effective
  symptomatic relief shortens (on versus off
  periods)
• The patient may suddenly turn off or fail to
  turn on
• Dopamine agonist treatment can cause psychiatric
  symptoms and is ineffective as long-term
  mono-therapy
• Non-motor symptoms of PD, such as autonomic
  dysfunction and depression, are generally not
  managed by these pharmacological treatments
• All current pharmacological treatments are purely
  symptomatic

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What about a cure?

• The problem of diagnosis.
• How do the neurons die?
• Abnormal protein aggregation
• Oxidative stress
• Mitochondrial dysfunction
• Proteosomal dysfunction
• Can this be slowed/halted?

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Conclusions

• Parkinsons disease is a significant cause of
  disability and death
• Currently it cant be cured and there are no
  therapies targeting degenerative mechanisms in
  current clinical use
• Symptomatic treatments are variably successful,
  depending on the disease type and stage
• Current research efforts aim to
• 1. Enable accurate, early diagnosis
• 2. Improve symptomatic treatment
• 3. Develop methods to slow neuron loss

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Wisdom of the ancients

• Kampavãta (kampa tremour)
• tremors of hand and feet, difficulty in body
  movements, disturbed sleep and dementia
• Stiffness, reduced desire for movement,
  depression, excessive salivation, sleepiness and
  fixed stare
• Successfully treated with Mucuna pruriens 9
  L-dopa