Term
Main Symptoms
Rigidity ( ↑muscle tone )
Postural problems
Tremor (70-80%)
Bradykinesia
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Definition
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Term
Clinical symptom seen after 70-80% loss of Dopamine in Nigrostriatal pathway
Substantia nigra---→Striatum (caudate-putamen)
Striatum: huge area of brain which receives sensory info from cortex then produce motor output |
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Definition
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Term
MPTP (opiate analog)
lipophilic, cross BBB
MAO-B in astrocytes convert MPTP---→MPP+
MPP+ is toxic and it kills DA.
Selegiline (Deprenil)- MAO-B inhibitor. It protects DA from toxic effect of MPTP |
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Definition
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Term
Why MPP+ target specifically to DA?
Dopamine Transportet (DAT)
only DA cells have DAT
Mazindol is a DAT blocker, it inhibit the uptake of MPP+
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Definition
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Term
Protection against MPP+
MAO-B inhibitor given before MPTP (full protection)
MAO_B inhibitor given after MPTP ( no protection)
DAT blocker given after (somewhat protected) |
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Definition
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Term
MPTP Toxicity
MPTP---→MPP+ by MAO_B
Mgets in DA by DAT
MPP+ inhibits electron transport chain in mitochondria,
DA runs out of ENERGY leading to cell death.. |
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Definition
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Term
Analogues of MPTP
Paraquat (herbicide),not a cause of PD
charged molecule, thus can't cross BBB
Rotenone (piscicide)
inhibit ETC of all cell in brain, can cause PD
low dose can kill DA
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Definition
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Term
L-DOPA (dopamine precursor)
not ideal given alone
Decorboxylase convert L-DOPA--→DA
some dopamine will convert to Nor-Adrenaline
NA gives side effects (Nausea, HTN) |
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Definition
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Term
L-DOPA+Carbidopa=Sinemet
inhibit decarboxylase thus 0 systemic side effect
more dopamine gets into the brain
Enhanced therapy with MAO inhibitor which would inhibit breakdown of DA in the brain. |
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Definition
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Term
In normal people,
L-DOPA convert to DA through DA terminal
In PD pt
DA terminal is lost, L-DOPA gets converted to DA through non-dopaminergic terminal. eg: serotonin terminal |
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Definition
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Term
Problem with L-Dopa/Carbidopa
On-Off effect
75% after 5 years experience dyskinesias
narow therapeutic window
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Definition
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Term
DA receptor agonists: Bromocriptine
useful in early PD to delay use of L-dopa
useful adjunct with L-dopa
adverse effects: nausea, hypotension,
CNS effect: pathological gambling |
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Definition
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Term
DA agonist + MAO-B inhibitor
postpone the need for L-DOPA
DA agonist-5 yrs
MAO-B inhibitors-1 yr
Smokers have less MAO activity which gives them certain level of protection over PD? |
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Definition
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