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Parkinson's Disease Robert L. Copeland, Ph.D. Howard University College of Medicine Department of Pharmacology 18 February 2002
Parkinson Disease ,[object Object]
Parkinson's disease was first formally described in " An Essay on the Shaking Palsy ," published in 1817 by a London physician named James Parkinson, but it has probably existed for many thousands of years. Its symptoms and potential therapies were mentioned in the Ayurveda, the system of medicine practiced in India as early as 5000 BC, and in the first Chinese medical text, Nei Jing, which appeared 2500 years ago.
[object Object],[object Object],[object Object]
Etiology ,[object Object],[object Object],[object Object]
Environmental factors and neurotoxins ,[object Object]
 
In Terms of Etiology and Clinical Picture, Major Symptoms Involve: ,[object Object],[object Object],[object Object],[object Object],[object Object]
Usually Other Accompanied Autonomic Deficits Seen Later in Disease Process: ,[object Object],[object Object],[object Object],[object Object],[object Object]
Parkinson Disease Neurochemistry ,[object Object]
[object Object],ACh DA
[object Object],[object Object],[object Object],[object Object]
Basal Ganglia ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The balance of the five large Subcortical Nuclei are responsible for smooth motor movements ,[object Object],[object Object],[object Object],[object Object]
Drug Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Agents that Increase Dopamine functions ,[object Object],[object Object],[object Object],[object Object],[object Object]
Dopamine and Tyrosine Are Not Used for Parkinson Disease Therapy ,[object Object],[object Object]
L Dopa Therapy for Parkinson Disease ,[object Object]
 
L Dopa- Pharmacokinetics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Effects of L Dopa on the Symptoms of Parkinson Disease ,[object Object],[object Object],[object Object],[object Object]
Effects of L Dopa on Behavior ,[object Object],[object Object]
Effects of L Dopa on Cardiovascular System ,[object Object],[object Object],[object Object],[object Object],[object Object]
Effects of L Dopa on Gastrointestinal System ,[object Object],[object Object],[object Object],[object Object]
GI cont. ,[object Object],[object Object],[object Object],[object Object]
Effects of L Dopa on Endocrine System ,[object Object],[object Object]
Adverse Effects with L Dopa ,[object Object],[object Object],[object Object]
Denervation Supersensitivity ,[object Object],[object Object],[object Object]
Adverse Effects of L Dopa ,[object Object],[object Object],[object Object],[object Object]
Adverse effects cont. ,[object Object],[object Object],[object Object],[object Object]
Long Term Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment ,[object Object]
"On/off" Effect ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
Drug Interactions with L Dopa ,[object Object],[object Object]
Drug Interactions cont ,[object Object],[object Object]
Drug Interactions cont ,[object Object],[object Object],[object Object]
Drug Interactions cont ,[object Object]
Other Drugs for Treating Parkinson Disease ,[object Object]
[object Object]
[object Object],[object Object]
[object Object],[object Object]
[object Object],[object Object]
The Protective Effects of Selegiline Although the factors responsible for the loss of nigrostriatal dopaminergic neurons in Parkinson's disease are not understood, the findings from neurochemical studies have suggested that the surviving striatal dopamine neurons accelerate the synthesis of dopamine, thus enhancing the formation of H 2 0 2  according to the following scheme.
Monoamine oxidase B Dopamine + 0 2  + H 2 0---------->  H 2 0 2  + NH 3  + 3,4 dihydroxyphenylacetaldehyde Glutathione peroxidase H 2 0 2  + 2 G S H ----------> G S S G + 2 H 2 0
[object Object],[object Object],[object Object]
Amphetamine for Treating Parkinson Disease ,[object Object]
Catechol-O-methyltransferase (COMT) inhibitors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Antimuscarinic Agents for Treating Parkinson Disease ,[object Object]
On the Horizon ,[object Object],[object Object],[object Object]
 
Risk of Parkinsonism in smokers is 20-70% less than non-smokers; nicotine may increase firing rate of dopaminergic neurons
[object Object],[object Object],[object Object]

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Parkinsons Disease Ii

  • 1. Parkinson's Disease Robert L. Copeland, Ph.D. Howard University College of Medicine Department of Pharmacology 18 February 2002
  • 2.
  • 3. Parkinson's disease was first formally described in " An Essay on the Shaking Palsy ," published in 1817 by a London physician named James Parkinson, but it has probably existed for many thousands of years. Its symptoms and potential therapies were mentioned in the Ayurveda, the system of medicine practiced in India as early as 5000 BC, and in the first Chinese medical text, Nei Jing, which appeared 2500 years ago.
  • 4.
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  • 40.
  • 41.
  • 42.
  • 43.
  • 44. The Protective Effects of Selegiline Although the factors responsible for the loss of nigrostriatal dopaminergic neurons in Parkinson's disease are not understood, the findings from neurochemical studies have suggested that the surviving striatal dopamine neurons accelerate the synthesis of dopamine, thus enhancing the formation of H 2 0 2 according to the following scheme.
  • 45. Monoamine oxidase B Dopamine + 0 2 + H 2 0----------> H 2 0 2 + NH 3 + 3,4 dihydroxyphenylacetaldehyde Glutathione peroxidase H 2 0 2 + 2 G S H ----------> G S S G + 2 H 2 0
  • 46.
  • 47.
  • 48.
  • 49.
  • 50.
  • 51.  
  • 52. Risk of Parkinsonism in smokers is 20-70% less than non-smokers; nicotine may increase firing rate of dopaminergic neurons
  • 53.