Parkinsons

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Classic motor signs of parkinson's disease
Resting tremor, postural instability, bradykinesia, rigidity
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non-motor signs of parkinsons
depression, cognitive decline, pain, autonomic dysfunction
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Potential causes of parkinson's 1
Genetics, 5% familial causes. Possibly related to mutations in the PARK1-16 genes, which is linked to the dysfunction of the ubiquitin proteosome system
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potential causes of parkinsons 2
MPTP can induce parkinsons in humans. Could be agrochemicals, pesticides, eg, Rotenone
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Major neuropathology
neuronal degredation of dopaminergic neurons in the substantia nigra pars compacta
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When do symptoms usually appear
following 60-80% striatal DA loss
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What do symptomatic drugs try to do
restore DA/ACh balance
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Examples of anticholinergics/muscarinic receptor antagonists
benzehexol, benzatropine
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The rationale behind anticholinergic drugs
loss of DA dis-inhibits of striatal cholinergic interneurons, so there is an increased release of ACh in striatum, increasing the firing of the indirect pathway. This contributes to the symptom of tremor
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Are anticholinergic drugs effective?
effective against tremor in around 30% of patients, but minimal effect against bradykinesia and rigidity. Side effects include confusion, mood changes, constipation, blurred vision, dry mouth
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Most common drug to treat parkinsons
L-Dopa, a natural precursor of dopamine that can cross the BBB
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Why is L-Dopa coadministered with peripherally acting DCC inhibitors?
because it is ~90% converted by DCC in the intestinal wall
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Examples of DCC inhibitors
Carbidopa (sinemet) and benserazide (madopar)
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Why would you give entacapone as an adjunct
it is a COMT inhibitor, to stop L-dopa being metabolised by COMT
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Side effects of L-DOPA
Nausea - domperidone is given as an adjunct, as it is a peripheral DA receptor antagonist. Also - hallucinations, confusion, insomnia, nightmares,
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Side effects of long term use of L-Dopa
on-off motor fluctuations, dyskinesias.
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Examples of Dopamine Receptor Agonists, as another treatment option
bromocriptine, pergolide, ropinirole, pramipexole.
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Why do DAr agonists show less on-off effect and dyskinesia
they have a longer half life so there is less plasma fluctuation
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Side effects of DAr agonists
Same as L-dopa
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An example of monoamine oxidase-B inhibitors
Selegiline
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Theory behind using MAO-B inhibitors
MAO-B is the principle route of DA metabolism in brain. By blocking DA metabolism, it means more DA is available. Often co-administed with L-DOPA so a lower amount can be given.
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Card 2

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non-motor signs of parkinsons

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depression, cognitive decline, pain, autonomic dysfunction

Card 3

Front

Potential causes of parkinson's 1

Back

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Card 4

Front

potential causes of parkinsons 2

Back

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Card 5

Front

Major neuropathology

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