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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.

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Parkinson’s Disease and Treatment

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  1. Parkinson’s Disease and Treatment Shalla Hanson Medicinal Chemistry April 2009

  2. 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.

  3. Major Symptoms-TRAP • Tremor • Rigidity • Akinesia/Bradykinesia • Postural Instability Other motor symptoms include: • Gait • Dystonia • Hypophonia • Drooling • Dysphagia • Fatigue • Akathesia

  4. Nonmotor Symptoms • 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

  5. Primary Known Causes • Idiopathic—majority of cases • Genetic • Drug induced—Calcium Channel Blockers • Toxins—Supported by the geographically varied incidence • Head Trauma • Cerebral Anoxia

  6. 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 substantianigra 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.

  7. Diagnosis • PET Scan—decreased dopaminergic activity in the substantia nigra • Unified Parkinsons Disease Rating Scale—cognitive interview • Normal CT • Normal MRI

  8. 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.

  9. Treatment • Education • Exercise • Nutrition • Psychiatric counseling

  10. 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

  11. Treatment • Oral Medications • MAO-B Inhibitors • Selegiline = most common • Dopamine Agonists • Ropinirole • Apomorphine • Lisuride • COMT Inhibitors (Catachol-O-methyl transferaseInh.) • Tolcapone • Entacapone • Stalevo = levodopa, carbadopa, and entacapone

  12. Treatment • Surgical Procedures • Deep Brain Stimulation • Creating a lesion in the subthalamic nucleus or globus pallidus

  13. Current Research • Gene Therapy • GAD = Glutamic Acid Decarboxylase • Deep Brain Stimulation • Controlled Impulses • Pallidotomy-not enough data to assess results well • Subthalotomy—improvements in contralateral rigidity • Subthalamic Deep Brain Stimulation—mimics Levodopa

  14. 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 nigralneurodegeneration: 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.

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