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Parkinson's Disease (symptoms (executive dysfunctions (attention,…
Parkinson's Disease
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Anatomy of Parkisons
Substantia Nigra is the most affected brain area by Parkinsonian degeneration. Loss of DA leads to overactivity of the indirect pathway and underactivity of the direct pathway.
Substantia Nigra projects to Striatum, splitting there into 2 pathways - direct and indirect. Indirect pathway responsible for stopping movements is inhibited by DA action on D2 receptors. Direct pathway initiates movements and is excited by DA action on D1 receptors.
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Drug treatment
L-DOPA
Unlike DA, DOPA can cross BBB in high doses
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side effects
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L-DOPA causes postural Hypotension in the PNS, by displacing NA in the vesicles in NA presynaptic terminals
Therapy effective up to 10 years. Afterwards all the DA neurons are dead and DA cannot be produced internally
Adjuncts
Carbidopa & Benserazide - block the synthesis
of DA from L-DOPA, but only outside the CNS (CTZ),
because they cannot cross BBB
Domperidone (D2R antagonist) - blocks the CTZ DA receptors, cannot cross the BBB
Selegiline - inhibits DA breakdown in CNS,
as it can cross the BBB
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