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Parkinson’s Disease Treatments:

Anticholinergic Drugs or Muscarinic Receptor Antagonists:
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These drugs act to block the acetylcholine muscarinic receptors and thus
cholinergic transmission
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The increased acetylcholine in the striatum results in activation of the
acetylcholine receptors in the striatum and subsequent over activity of the
indirect pathway
...

When acetylcholine muscarinic antagonists are used, there is a marked reduction
in the tremor in around 30% of patients
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Side Effects 
1) Sometimes the cholinergic blockage itself can increase confusion and cause
mood changes
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3) Blurred vision
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This is where there is excess salvia production and accumulation due to
reduced ability to salvia
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Examples  BENZHEXOL + BENZATROPINE
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The drug is delivered as a natural dopamine precursor so that it can use an
amino-acid transporter to enter the brain (dopamine alone cannot do this)
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However the enzyme Dopa Decarboxylase is also present in the periphery in the
intestinal wall
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To avoid the peripheral metabolism of Levodopa, levodopa is co-administered
with a peripherally-acting Dopamine Decarboxylase inhibitor
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Some of the Levodopa may be converted by the plasma Catechol-O-MethylTransferase (COMT) enzyme
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➢ To avoid this a COMT inhibitor is used (like entacapone) as an adjunct
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The Dopamine Decarboxylase in the brain produces Dopamine
Dopaminergic and Serotinergic neurones
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2) Activity in the direct (D1) and indirect (D2) pathways is normalised for
better motor function
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Acute side-effects of Levodopa:
1) Nausea may occur due to residual peripheral dopamine receptor activation
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2) Postural hypotension especially in people on anti-hypertensive drugs
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This is
because the extra Dopamine in ‘normal areas’ drives the limbic system =
psychosis
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➢ These chronic side-effects will affect around 1/3 of patients
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❖ There may be more periods of freezing which can last for variable
times
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❖ The efficacy of the drug has diminished over time and a larger
dose is needed to achieve same effect
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❖ These motor fluctuations may be due to the way in which
levodopa is administered (in bulk single doses) which causes the

plasma levels of levodopa to fluctuation
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❖ Motor fluctuations may also be due to less ability to be able to
store the Dopamine due to degeneration of the neurones
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❖ The dyskinesias tend to affect the face and the limbs
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❖ As disease progresses the therapeutic window of Levodopa
narrows = increased chance of dyskinesia if dose too high
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❖ Amantadine (NMDA-type glutamate receptor blocker) is the only
drug which offers relief
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Dopamine Receptor Agonists:
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Dopamine receptor agonists are the first line treatment for Parkinson’s
Disease
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They reduce the symptoms of Parkinson’s by activating the striatal D2
receptors
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These drugs are not affected by progressive neurodegeneration and don’t need
any conversion for their action
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Acute side-effects are similar to those for Levodopa
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There is reduced chance of
developing dyskinesia and also they have a longer plasma ½ life so there is less
plasma fluctuation and thus less on-off effects
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Eventually they will need Levodopa but the use of these drugs means that
Levodopa can be started later and even at a lower dose (if dopamine agonists are
used as an adjunct) and hence its side-effects are less likely to occur
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This enzyme breaks dopamine down into DOPAC (dihydroxyphenylacetic acid)
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These are used as adjuncts and help
to lower the levodopa dose needed = reduces chance of dyskinesia
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Non-selective MAO-inhibitors cause the cheese reaction (because tyrosine can
no longer be broken down) BUT because selegiline is selective of MAO-B, MAOA is still available to break down tyrosine
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This is effective as a monotherapy in early Parkinson’s
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Surgical Approaches to Parkinson’s Disease:
1) Neuroablative Surgery:
➢ This was popular prior to levodopa
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➢ Thalamotomy  used in tremor dominant cases
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➢ Subthalamotomy  used for improving rigidity, bradykinesia + Levodopa
induced dyskinesias
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➢ Disadvantages of this ablative therapy included:
1) Irreversible
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3) Intracerebral haemorrhage may occur
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2) Deep Brain Stimulation:
➢ This is now more popular as it is REVERSIBLE
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This probably involves a depolarising
block of nerve conduction
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➢ Procedure can be graded – increase stimulation as needed and when
needed
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Failings of Current Treatments:
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The current treatments are not cures for Parkinson’s and do not slow its
progression
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They only treat some of the symptoms and postural imbalance is still present
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The treatments do not address the progressive degeneration of the cells

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