parkinson Flashcards
(113 cards)
1
Q
what are 5 movement disorders
A
tremor chorea athetosis dystonia tics
2
Q
what is tremor
A
rhythmic oscillation around a joint
3
Q
what is postural tremor
A
tremor while trying to maintain posture (eg. standing still), also exists as benign essential familial tremor
4
Q
when is tremor associated with parkinsons (2 things)
A
rigidity and impairment of voluntery movement
5
Q
what is intentional tremor
A
when you have a tremor when you want to move
6
Q
what can intentional tremors be associated with (3 things)
A
lesions of brainstem (cerebellum), alcohol, drug toxicity
7
Q
what does chorea mean (1 word)
A
dance
8
Q
what types of movement characterize chorea
A
irregular, unpredictable movements
9
Q
what does chorea do to voluntary activity
A
impair proximal muscle, resulting in violent movement
10
Q
what are some of the movements called in chorea and why
A
ballistic movements - more violent because they arise from proximal movements (like move whole arm instead of just hand)
11
Q
what can cause chorea (3)
A
hereditary
general medical disorders
drug therapies
12
Q
what is athetosis
A
slow involuntary writhing movements (like twisting squirming controtions)
13
Q
what is dystonia
A
sustained movement with abnormal posture
14
Q
what causes dystonia and athetosis (3)
A
perinatal damage (right before and after birth), CNS lesions, drug treatments
15
Q
what are Tics
A
sudden coordinated abnormal movements
16
Q
what is tourettes syndrome
A
multiple chronic tics
17
Q
what kind of drugs can induce parkinsons-like syndroms (2)
A
dopamine antagosnists or drugs that destroy DA releasing neurons (MPTP)
18
Q
where do the Dopaminergic cells come from
A
substantia nigra compcta
19
Q
where do the DA releasing cells project to (which neurons and where)
A
GABAergic cells in the striatum
20
Q
what does DA do to GABAergic cells in striatum
A
inhibit
21
Q
what does ACh do to GABAergic cells in striatum
A
excite
22
Q
what causes parkinsons disease (which neurons are effected, what does this cause)
A
loss of DA releasing cells, less inhibition on GABA cells, so excess GABA release
23
Q
what causes huntingtons disease (which neurons are effected, what does this cause)
A
Loss of cholinergic input, GABA cells die off, less GABA inhibition (so you get violent movements)
24
Q
what is another name for parkinsonism
A
paralysis agitans
25
what 4 things characterize parkinsons
- rigidity
- bradykinesia (slow movement)
- tremor
- postural instability
26
what usually causes parkinsons
unknown (idiopathic)
27
what may cause early onset parkinsons
genetics
28
is parkinsons progressive
yes
29
what is the frequency of the resting tremor
4-6Hz
30
what is the word for Parkinsonian movements when the hands arent extended
"pill rolling"
31
what is the parkinsons gait? describe 3 characteristics
stooped posture, flexion at knees, hips and neck, small shuffling steps, emphasized when turning, difficulty initiating movement
32
can you cure parkinsons
no
33
can you stop parkinsons progression
no
34
what is the primary therapy for Parkinson's
enhance DA levels in striatum
35
what are 2 primary therapies to enhance DA levels in the striatum (which drugs/ kind of drugs)
levodopa and dopamine agonists
36
what is secondary therapy for Parkinson's
enhance DOPA entry into and persistance in brain
37
which drug helps enhance DOPA entry into brain + persistence in brain
carbidopa
38
what G protein for D1
Gs
39
what G protein for D2
Gi
40
where are D1 neurons located (2)
- on DA neurons in nigra
| - presynaptic terminals of cortical projections to striatum (glu receptive neurons)
41
where are D2 neurons located
- postsynaptic on striatal GABA cells
| - presynaptic on basal ganglia inputs to nigra
42
which DA receptor action of dopamine are antiparkinsonian
D2 agonists
43
do you need D1 or D2 action to do antiparkinsons therapy
mostly D2 but some D1 is needed
44
does dopamine pass the BBB
no
45
why does dopamine activation of D2 receptors have antiParkinson's effects
because D2 activation on striatal GABA cells inhibits extra GABA release (less GABA release so less of the Parkinson's stiffness)
46
why does D2 antagonism induce Parkinson's like symptoms
because D2 agonism helps reduce GABA release. D2 antagonism is similar to the death fo DA releasing neurons
47
what is Levodopa's relation to DA
it is a metabolic precursor to DA synthesis (AMD bypasses the rate-limiting synthesis step)
48
what step of DA synthesis does levodopa bypass
the rate-limiting step (tyrosine hydroxylase)
49
does levodopa penetrate the BBB (how much)
yes at 1-10%
50
where is levodopa transformed into DA
in the brain and periphery
51
why is levodopa allowed to enter the brain
because it looks like an amino acid
52
where is levodopa absorbed
in the small intestine
53
why dont you want to take levodopa with food
because the amino acids from food with compete with levodopa with transporter
54
when do plasma concentrations of levodopa peak in the blood (how long, time)? what is the plasma 1/2 life of levodopa?
1-2 hours. half life: 1-3 hours with variability
55
what are the metabolites of levodopa (2)
- homovanillic acid HVA
| - DOPAC (dihydroxyphenylacetic acid)
56
what % of unmetabolized levodopa enters the brain
1-3%
57
what kind of drug is coadministered with levodopa
periphreal DOPA decarboxylase inhibitor
58
why would you want to administer a periphreal DOPA decarboxylase inhibitor with levodopa
to help prevent its breakdown outside the brain so more can come in
59
what is Carbidopa's relation to the dopamine pathway
it is structurally similar to DOPA
60
what is the mechanism of action of carbidopa
inhibits DOPA-decarboxylase, preventing breakdown of levadopa in the peripheries before it enters the brain
61
what turns L-DOPA into dopamine
dopa decarboxylase
62
how is carbidopa given in treatment
ratio of 1:10 or 1:4 with levodopa
63
what does carbidopa permit with levodopa
up to 10% of levodopa to enter the brain (increases levodopa entering into brain)
64
what is sinemet
carbidopa + levodopa
65
what is the ratio of carbidopa and levodopa in sinemet
initial treatment and final
25 carbidopa:100 levodopa
increases to
25 carbidopa:250 levodopa
(since efficacy of levodopa decreases with treatment)
66
how does the effect of levodopa change with treatment
it decreases inefficacy
67
what drugs do you often add to sinemet in advanced stages
add dopaminergics
68
what are some gastrointestinal effects of levodopa (3)
nausea vomit weight loss
69
what are 3 ways to help prevent the GI issues of levodopa
- smaller more frequent doses
- using carbidopa/perhipheral DDC inhibitors to decrease the amont of free DA in the periphery
- antacids
70
do antiemetic phenothiazines help with GI issues with levodopa
no
71
what are cardiovascular effects of levodopa
tachycardia, arrhythmia, postural hypotension
72
what causes the adverse cardio effects of levodopa
increase catecholamine formation in periphery (due to DA -> NA -> A)
73
what can help counteract the cardio effects of levodopa and how
carbidopa/peripheral DDC inhibitors because it reduces the circulating dopamine
74
why does dyskinesia vary with levodopa use
because its dose-related with individual responses
75
what can help the dyskinesias with levodopa
- improvement as patient gets used to levodopa treatment
- drug holidays
- surgery (reduce doses of levodopa needed)
76
what are the adverse behavioural effects of levodopa (6)
depression, anxiety, agitation, confusion, delusions, mood changes
77
list 5 negative side effects of levadopa
GI related (nausea and vomiting)
CV (tachycardia)
Dyskinesias
Behavioral effects (depression, anxiety, delusion)
Fluctuations in response
On and Off phenomena
78
what are some drugs that can help with the behavioural effects of levodopa
some antipsychotics
79
what 2 things cause/effect the fluctuation of response of levodopa
- increasing frequency with treatment (levodopa become more ineffective)
| - some related to timing of doses (wearing-off, end-of dose akinesa)
80
what is the on-off phenomenon
periods of akinesia alternate with mobility and dyskenesia (no movement and too much movement)
81
what are 2 ways to help reduce on-off phenomenon
reduce protein intake (DA is a tyrosine derivative)
| controlled release sinemet or COMT inhibitors
82
what are drug holidays? why are they controversial
taking breaks to help reduce adverse effects
needs very careful supervision since stopping levodopa abruptly can lead to akinesia
benefits are short lived
83
what 4 benefits of using DA agonists
- they dont have potentially toxic metabolites
- they do not compete with other substances for transporters
- they are receptor selective
- can be used in combination therapy with levodopa/carbidopa
84
how do you use dopamine agonists in treatment
with adjuct to levodopa/carbidopa, or to gradually replace to levodopa
85
what are 2 examples of dopamine agonists
bromocriptine and pergolide
86
which receptor does bromocriptine bind
agonist at D2
87
which receptor does pergolide bind
mixed D1 and D2 agonist
88
is pergolide or bromocriptine better
pergolide
89
what do bromocriptine and pergolide do to the required dose of levodopa
lower
90
what are the adverse effects of bromocriptine and pergolide
similar to levodopa but less severe (but mental symptoms are worse)
91
name two ergot derivative dopamine agonists
bromocriptine and pergolide (older ones)
92
which dopamine agonists are the older drugs
bromocriptine and pergolide
93
name two non-ergot related dopamine agonists
pramipexole and ropinirole
94
how are bromocriptine and pergolide used in therapy compared to pramipexole and ropinole
bromochiptine and pergolide are often given with levodopa
pramipexole and ropinole are given alone
95
which DA receptors does pramipexole bind
D3 (D2 class) agonist
96
which DA receptors does ropinirole bind
pure D2 agonist
97
what are the adverse effects like for pramipexole and ropinirole
similar to levodopa
98
what are 2 benefits of using pramipexole
effective in advanced parkinsons and firstline therapy for younger patients to protect remaining neurons
| possible neuroprotective effect
99
what does MAO B metabolize
dopamine
100
what are selegiline/rasagiline
MAO B blocker
101
name a MAO B inhibitors used in Parkinson's treatment
Selegine
102
when is selegiline used in treatment and how
with levodopa when its effects start declining
103
what are some contraindications for selegiline
patients that use TCAs or SSRIs
104
what does COMT do
metabolizes levodopa
105
what happens to COMT levels with more DDC inhibition
increase levels (since there is excess L-DOPA lying around)
106
what are 2 examples of COMT inhibitors
tolcapone and entacapone
107
where does tolcapone act
centrally and peripheral (hepatotoxic)
108
where does entacapone act
only peripherally
109
what are some side effects of tolcapone and entacapone +1 really bad one
similar to levodopa, diarrhea, orange urine, orthostatic hypotension
tolcapone is hepatotoxic
110
how does tolcapone and entacapone reduce the amount of levodopa needed
(COMT inhibitors)
increases its half life by inhibiting L-DOPA breakdown
111
what is amantadine
antiviral that blocks NMDA receptors on cholinergic neurons, may increase brain dopamine
112
when are using anticholinergics the best for parkinsons
when the tremor is the main symptoms (NOT rigidity, brakykinesia)
113
why can anticholinergics be good for parkinsons
because a lack of DA release means overbalance of cholinergic excitation of GABA neurons in the basal ganglia
