Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medsci305 > Lecture 15: Parkinson's disease > Flashcards

Lecture 15: Parkinson's disease Flashcards

1
Q

What is parkinson’s disease?

A
  • chronic progressive neurodegenerative disorder with currently no cure
  • but is one of the few neurodegenerative disorders with treatments
  • affects 1% of population over 65, and 4% over 85
  • about 18,000 sufferers in NZ
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How has the prevalence of parkinson’s changed ?

A
  • used to almost always see onset later in life, but now at least 5% of patients present with early onset parkinson’s (before 40 years)
  • treatment is very expensive with statistics showing each patient spending on average 200,000USD/year
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the clinical symptoms of parkinson’s?

A
  • tremor in hands/arms/legs
  • pill rolling tremor
  • rigidity/stiffness of trunk/limbs
  • bradykinesia/slowness of movement
  • muscle rigidity/increased resistance to passive movement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What do the clinical symptoms of parkinson’s relate to?

A
  • loss of cells in the basal ganglia portion of the brain which is involved in the initation of movements
  • parkinson’s patients have trouble getting out of the chair but once they’re out they okay.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the pathology of parkinson’s disease?

A
  • exact initial cause unknown but we do know the population of cells selectively affected
  • the substantia nigra contains a population of dopamine cells which are part of the basal ganglia network. these project axons out into the striatum where they release dopamine in the striatum
  • the dopamine D1 and D2 receptors are found in the striatum.
  • the terminals bind and act as an agonist at these receptors and further stimulate neurotransmission
  • parkinson’s = selective loss of dopamine cells in substantia nigra.
  • but DA cells in other regions of brain not as affected
  • as cells in the SN retract, axons die off
  • no longer have axons projecting into striatum and therefore no more DA released to stimulate the D1 and D2 receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the role of dopamine in movement?

A

-dopamine is required to relay messages between the substantia nigra to the striatum to produce smooth, purposeful movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What causes parkinson’s?

A
  • quite possible for each patient to have a different primary cause
  • 10% have genetic or familial PD, found by genetic mutation in genes like Parkin
  • majority of patient have sporadic PD where there isn’t a patient history
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the main theories of initial cause of parkinson’s disease?

A
  1. patients developing PD have a reduction in mitochondrial complex 1 activity
  2. environmental toxins
  3. head injury
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the mitochondrial complex 1 activity theory in the cause of PD?

A
  • This is where there is an impairment in mitochondrial activity resulting in the formation of reactive oxygen species which are toxic to cells
  • however, the reason why DA cells in the SN are substantially affected are unknown
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the environmental toxin theory in the cause of PD?

A
  • derost dust used in farmng to kill white butterflies found to selectively kill dopamine neurons
  • there have been epidemiological studies done to support this
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the types of clinical treatment for parkinson’s?

A 
L-dopa
carbidopa
COMT inhibitor
Bromocriptine and pergolide
Deprenyl/selegiline HCl
Amantadine
Anticholinergic agents benztropine or atropine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is L dopa?

A
  • levo dopa
  • mainstay treatment for PD
  • it is a synthetic pro-drug form of dopamine which can cross the bbb
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is dopamine synthesised?

A

Dopamine is synthesised from tyrosine

  • tyrosine hydroxylase converts this to form DOPA
  • DOPA decarboxylase turns this into dopamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the clinical effect of Ldopa?

A

-usually see patients in the first 5 years of treatment having a significant reduction in PD symptoms and are pretty much back to normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens after ~5 years of Ldopa treatment?

A
  • start to get a wearing off effect where the period between effective doses becomes shorter.
  • patients will also experience on off effects which occurs due to unpredictable effects of DA.
  • when the neuron becomes sick it starts to dump out excessive amounts of DA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What causes the on off effects of long term Ldopa use?

A
  • On symptoms caused by L dopa working

- Off symptoms when it isn’t working

17
Q

What are dyskinesias?

A
  • there are involuntary movements which occur randomly as a side effect of long term L dopa use.
  • due to cells releasing way too much dopamine
18
Q

What are the Ldopa resistant symptoms?

A
  • patients response to the drug essentially changes, and may require more freuqent dosing or higher concentrations of L dopa.
  • As natural disease progression occurs, the cells are still progressively declining, so even though Ldopa concentration is increased patient may still be resistant to the drug
19
Q

What is carbidopa?

A
  • often formulated in combination with Ldopa to ensure better control of Ldopa going into the brain
  • Dopa decarboxylase may metabolise Ldopa into DA while it is in the body as the enzyme is also found all around the body
  • this would mean that DA would be degraded in the body before reaching the bbb
  • Carbidopa basically added to attach to peripheral dopamine decarboxylase to allow L dopa to be metabolise by the decarboxylase in the brain for its effect.
  • it also reduces systemic side effects of DA
20
Q

What are COMT inhibitors?

A

COMT is an enzyme that can convert Ldopa into 3-OMD

catechol-o-methyl transferase inhibitors are also a common adjunctive to L-dopa therapy.
-these make sure that L dopa is not broken down before reaching the bbb.

21
Q

What are bromocriptine and pergolide?

A
  • DA receptor agonists
  • mimic effect of DA in the striatum by binding to the D1 and D2 DA receptors
  • DA transmission can be continued
  • these agents are potent D2 agonists, and weak D1 agoinsts as D2 is inhibitory.
  • we want the inhibitory dopamine neurotransmission to decrease
  • these are commonly used with L dopa in particular when the effects of L dopa start to wear off
22
Q

What is deprenyl/selegiline HCl?

A
  • MAO inhibitors which are selective for monoamine B
  • particularly interested in the presynaptic terminal.
  • this breaks dopamine down to dopac and allows it to be recycled and released again
  • MAO B can be found in the synaptic cleft as well.
  • the drugs also bind to this to increase the amount of DA in the synaptic cleft.

-Deprenyl is often given with Ldopa to enhance its effects.

we want to maintain and further stimulate the increased amounts of DA to be recycledand released and remaining in the synaptic cleft

23
Q

What is amantadine?

A
  • antiviral agent used to treat influenza,
  • unsure of mechanism, but found to have ability to increase DA release by inhibiting DA uptake.
  • also has direct stimulatory effect on D2 receptors
24
Q

What are anticholinergic agents Benztropine and Atropine?

A
  • used before Ldopa was developed
  • rationale is that muscarinic receptors also play an important role in PD. they play an excitatory effect.
  • Also have presynaptic inhibitory effect on dopamine release and so will inhibit this release.
  • as PD progresses, there is breakdown of DA cells in SN. When DA reduces, the excitatory effects of ACh musarinic receptors take over resutling in tremor and rigidity which we aim to reduce by blocking these receptors.
  • inhibiting these receptors also stops the inhibition of DA release in the presynaptic terminal
25
Q

What are the future therapies for parkinsons?

A
  • developing long term controlled release of dopamine
  • development of drugs to reduce incidence of side effects
  • cell transplantation
  • gene therapy
26
Q

What are the limitations for future therapies of parkinsons?

A

-as we are dealing with a disease where people may not have the same initial cause, the new therapies could also have different reactions in the patients and may not work for everyone.

27
Q

What are the implications of long term controlled release dopamine?

A
  • allows patients to not have to take oral Ldopa

- L dopa will be released in more regulated manner which may control on/off effects and side effects

28
Q

What are the implications with developing drugs that reduce the incidence of side effects?

A
  • Found that patients experiencing on/off effects from taking L-dopa in early parkinson’s could be corrected (stop having the side effects) if ecstasy was taken.
  • ecstasy increases 5-HT levels
29
Q

What are the implications for cell transplantation for PD?

A
  • have tried fetal DA cells into patients previously, now looking at human stem cells
  • found to be effective in some patients,
  • unfortunately these cells also develop pathological markers of PD and start to die
30
Q

What are the implications of gene therapy for PD?

A
  • a lot of compounds/treatments so far have aimed to protect DA cells in SN, but are often too large to cross the bbb
  • gene therapy could allow the use of viral vectors to put cDNA for the therapeutic gene of interest into the area (SN) to target DA cells and protect remaining DA cells

-another type of gene therapy is inserting GAB (precursor of GABA) into the nucleus to inhibit the excitatory effects.

Medsci305 (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions