Transcript Parkinson`s Disease and Treatment

Parkinson’s Disease and
Treatment
Shalla Hanson
Medicinal Chemistry April 2009
Description of Disease
• Parkinson’s disease (PD) is typically considered
a chronic, progressive neurodegenerative
movement disorder. However, it is now
known to have variety of nonmotor symptoms
as well.
Major Symptoms-TRAP
• Tremor
• Rigidity
• Akinesia/Bradykinesia
• Postural Instability
Other motor symptoms include:
• Gait
• Dystonia
• Hypophonia
• Drooling
• Dysphagia
• Fatigue
• Akathesia
Nonmotor Symptoms
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Mood—20-80% suffer from depression.
Behavior—indirectly, e.g., a result of dementia, depression.
Thinking-slowed reaction time and executive dysfunction
Sensation—impaired sense of smell
Excessive daytime sleep, insomnia, and REM sleep
disturbances.
Vision problems
Impaired proprioception
Oily skin
Weight loss
Incontinence
Constipation
Drooling
Primary Known Causes
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Idiopathic—majority of cases
Genetic
Drug induced—Calcium Channel Blockers
Toxins—Supported by the geographically
varied incidence
• Head Trauma
• Cerebral Anoxia
Pathophysiology
• Decreased stimulation of the motor cortex by the basal
ganglia, usually due to the inadequate production and
action of dopamine (produced in the dopaminergic
neurons of the brain.)
• The specific region affected seems to be the pars
compacta in the substantia nigra where there is a
marked loss in dopaminergic cells.
• We also see a considerably high activity in the cells of
the Subthalamic nucleus, which inhibits movement.
• High presence of Lewy bodies in dopaminergic cells.
Diagnosis
• PET Scan—decreased dopaminergic activity in
the substantia nigra
• Unified Parkinsons Disease Rating Scale—
cognitive interview
• Normal CT
• Normal MRI
History
• PD was first described in detail by James Parkinson in 1817
in “An Essay on the Shaking Palsey.”
• Carlsson in 1950, determined that dopamine was a
neurotransmitter and was exceptionally concentrated in
the basal ganglia.
• Carlsson’s research later showed that Reserpine
demonstrates a correlation between motor impairment
and decreased dopamine levels. L-Dopa also given to
animals which alleviated symptoms and initiated medicinal
therapies for PD in 1967.
• In California in 1980 a group of opiate addicts consumed
MPTP N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and
revealed a pro-toxin, allowing another animal model of PD.
Treatment
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Education
Exercise
Nutrition
Psychiatric counseling
Treatment
• Oral Medication
– L-Dopa (aka Levodopa)
– Most popular treatment
– Form of dopamine which
is able to cross the BBB
through transport in L-AA
system and can then be
metabolized to dopamine.
– Sinemet = levodopa +
carbidopa
Treatment
• Oral Medications
– MAO-B Inhibitors
– Selegiline = most common
• Dopamine Agonists
– Ropinirole
– Apomorphine
– Lisuride
• COMT Inhibitors (Catachol-O-methyl transferase Inh.)
– Tolcapone
– Entacapone
– Stalevo = levodopa, carbadopa, and entacapone
Treatment
• Surgical Procedures
– Deep Brain
Stimulation
– Creating a lesion in
the subthalamic
nucleus or globus
pallidus
Current Research
• Gene Therapy
– GAD = Glutamic Acid Decarboxylase
• Deep Brain Stimulation
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Controlled Impulses
Pallidotomy-not enough data to assess results well
Subthalotomy—improvements in contralateral rigidity
Subthalamic Deep Brain Stimulation—mimics
Levodopa
Works Cited
Britton, Thomas C. "NONMOTOR ASPECTS OF PARKINSON'S DISEASE."
Current Medical Literature: Neurology 20 (2004): 45-50.
"Parkinson's Disease." Current Medical Literature: Neurology 23
(2007): 44-48.
Marceglia, Sara, and Alberto Priori. "Sex, genes, hormones and nigral
neurodegeneration: two different Parkinson's diseases in males and
in females." Future Neurology 2 (2007): 499-503.
"Literature Review: Pathophysiology." Current Medical Literature:
Parkinson's Disease 5 (2003): 59-61.
"Literature Review: Medical Treatment." Current Medical Literature:
Parkinson's Disease 5 (2003): 66-70.
"Literature Review: Surgical Treatment." Current Medical Literature:
Parkinson's Disease 5 (2003): 71-72.