parkinson Flashcards
(147 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 tp maintain posture
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
which tremor is associated with essential (familial tremor)
A
postural tremor
7
Q
what can intentional tremors be associated with (3 things)
A
lesions of brainstem (cerebellum), alcohol, drug toxicity
8
Q
what does chorea mean (1 word)
A
dance
9
Q
what types of movement characterize chorea
A
irregular, unpredictable movements
10
Q
what does chorea do to voluntary activity
A
impair
11
Q
which muscles are most affected by chorea
A
proximal muscles
12
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)
13
Q
is chorea hereditary
A
sometimes
14
Q
what can cause chorea (3)
A
hereditary
general medical disorders
drug therapies
15
Q
what is athetosis
A
slow writing movements (like twisting squirming controtions)
16
Q
what is dystonia
A
sustained movement with abnormal posture
17
Q
what causes athetosis (3)
A
perinatal (right before and after birth) damage, CNS lesions, drug treatments
18
Q
what causes dystonia (3)
A
perinatal damage (right before and after birth), CNS lesions, drug treatments
19
Q
what are Tics
A
sudden coordinated abnormal movements
20
Q
what is tourettes syndrome
A
multiple chronic tics
21
Q
what kind of drugs can induce parkinsons-like syndroms (2)
A
dopamine antagosnists or drugs that destroy DA releasing neurons
22
Q
where do the Dopaminergic cells come from
A
substantia nigra compcta
23
Q
where do the DA releasing cells project to (which neurons and where)
A
GABAergic cells in the striatum
24
Q
what does DA do to GABAergic cells in striatum
A
inhibit
25
what does ACh do to GABAergic cells in striatum
excite
26
what causes parkinsons disease (which neurons are effected, what does this cause)
loss of DA releasing cells, less inhibition on GABA cells, so excess GABA release
27
what disease is characterized by a loss of nigral DA cells
parkinsons
28
what causes huntingtons disease (which neurons are effected, what does this cause)
Loss of cholinergic input, GABA cells die off, less GABA inhibition (so you get violent movements)
29
what disease is characterized by a loss of cholinergic input onto GABA cells in striatum
huntingtons
30
what disease is characterized by a loss GABA cells in striatum
huntingtons
31
what is another name for parkinsonism
paralysis agitans
32
what 4 things characterize parkinsons
- rigidity
- bradykinesia (slow movement)
- tremor
- postural instability
33
what usually causes parkinsons
unknown (idiopathic)
34
what may cause early onset parkinsons
genetics
35
is parkinsons progressive
yes
36
what is the frequency of the resting tremor
4-6Hz
37
what is the word for movements when the hands arent extended
"pill rolling"
38
what is the parkinsons gait +where flexion (3 places)
stooped posture, flexion at knees, hips and neck
39
what kind of steps do people with parkinsons take+ what is it like when they turn
small shuffling steps, emphasized when turning
40
is it difficult to initiate or change movements with parkinsons
yes
41
can you cure parkinsons
no
42
can you stop parkinsons progression
no
43
what % of neuron loss do you start getting parkinsons symptoms
80%
44
what is the primary therapy for Parkinson's
enhance DA levels in striatum
45
what are 2 ways to enhance DA levels in the striatum (which drugs/ kind of drugs)
levodopa and dopamine agonists
46
what is secondary therapy for Parkinson's
enhance DOPA entry into and persistance in brain
47
which drug helps enhance DOPA entry into brain + persistence in brain
carbidopa
48
what G protein for D1
Gs
49
what G protein for D2
Gi
50
what does D1 do to adenylyl cyclase
induce
51
where are D1 neurons located (2)
- on DA neurons in nigra
| - presynaptic terminals of cortical projections to striatum (glu receptive neurons)
52
what do D2 to adenylyl cyclaes activity
inhibit
53
where are D2 neurons located
- postsynaptic on striatal GABA cells
| - presynaptic on basal ganglia inputs to nigra
54
which effects of dopamine (agonism/anta) on which receptors can induce Parkinson's symptoms (D1 D2)
D2 antagonists of dopamine
55
which DA receptor action of dopamine are antiparkinsonian
D2
56
do you need D1 or D2 action to do antiparkinsons therapy
mostly D2 but some D1 is needed
57
does dopamine pass the BBB
no
58
why are D2 actions of dopamine antiParkinson's
because D2 activation on striatal GABA cells inhibits extra GABA release (less GABA release so less of the Parkinson's stiffness)
59
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
60
what is Levodopa's relation to DA
it is a metabolic precursor to DA synthesis (AMD bypasses the rate-limiting synthesis step)
61
what step of DA synthesis does levodopa bypass
the rate-limiting step
62
does levodopa penetrate the BBB (how much)
yes at 1-10%
63
where is levodopa transformed into DA
in the brain and periphery
64
why is levodopa allowed to enter the brain
because it looks like an amino acid
65
where is levodopa absorbed
in the small intestine
66
how easily is levadopa absorbed
fast and easy
67
why dont you want to take levodopa with food
because the amino acids from food with compete with levodopa with transporter
68
how does levodopa get absorbed into the blood
absorbed in the small intestine via amino acid transporters
69
when do plasma concentrations of levodopa peak in the blood (how long, time)
1-2 hours
70
what is the plasma 1/2 life of levodopa
1-3 hours (considerable variability)
71
what are the metabolites of levodopa (2)
- homovanillic acid HVA
| - DOPAC (dihydroxyphenylacetic acid)
72
what % of unmetabolized levodopa enters the brain
1-3%
73
what is the therapeutic goal of levodopa use
increase levodopa into the CNS
74
what kind of drug is coadministered with levodopa
periphreal DOPA decarboxylase inhibitor
75
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
76
what is Carbidopa's relation to the dopamine pathway
it is structurally similar to DOPA
77
what is the mechanism of action of carbidopa
inhibits DOPA-decarboxylase
78
what are the intermediates between tyrosine and dopamine
just DOPA (L-DOPA)
79
what turns L-DOPA into dopamine
dopa decarboxylase
80
how is carbidopa given in treatment
ratio of 1:10 or 1:4 with levodopa
81
what does carbidopa permit with levodopa
up to 10% of levodopa to enter the brain (increases levodopa entering into brain)
82
what is sinemet
carbidopa + levodopa
83
what is the ratio of carbidopa and levodopa in sinemet
initial treatment and final
25 carbidopa:100 levodopa
increases to
25 carbidopa:250 levodopa
(efficacity of levodopa decreases with treatment)
84
how does the effect of levodopa change with treatment
it decreases inefficacy
85
what drugs do you often add to sinemet in advanced stages
add dopaminergics
86
what are some gastrointestinal effects of levodopa (3)
nausea vomit weight loss
87
what causes vomiting with levodopa
DA action at the vomiting center
88
where is the vomiting centre
in CNS but outside BBB
89
why is there more vomiting centre activation with levodopa
because levodopa increases DA which activates the vomiting center
90
what are 3 ways to help prevent the GI issues of levodopa
- smaller more frequent doses
- using carbidopa too
- antacids
91
do antiemetic phenothiazines help with GI issues with levodopa
no
92
what are cardiovascular effects of levodopa
tachycardia, arrhythmia, postural hypotension
93
what causes the adverse cardio effects of levodopa
increase catecholamine formation in periphery
94
what can help counteract the cardio effects of levodopa and how
carbidopa because it reduces the circulating dopamine
95
what % of people get dyskinesias with levodopa
80%
96
why does dyskinesia vary with levodopa use
because its dose-related with individual responses
97
what can help the dyskinesias with levodopa
- improvement with levodopa alone
- drug holidays
- surgery (reduce doses of levodopa needed)
98
what are the adverse behavioural effects of levodopa (6)
depression, anxiety, agitation, confusion, delusions, mood changes
99
are there more of lessBEHAVIOURAL effects with just levodopa or levodopa and a DDC inhibitor (carbidopa)
worse with both drugs than just levodopa
100
what are some drugs that can help with the behavioural effects of levodopa
some antipsychotics
101
what 2 things cause/effect the fluctuation of response of levodopa
- increasing frequency with treatment
| - some related to timing of doses (wearing-off, end-of dose akinesa)
102
what is the on-off phenomenon
periods of akinesia alternate with mobility and dyskenesia (sudden, sometimes unpredictable changes in a PD patient's symptoms, varying between mobility (usually with dyskinesia) and immobility)
103
what is the mechanism of the on-off phenomenon
its unknown
104
what are 2 ways to help reduce on-off phenomenon
reduce protein intake (DA is a tyrosine derivative)
| controlled release sinemet or COMT inhibitors
105
is on-off phenomenon related to dose timing
no
106
what are drug holidays and the point of them
taking breaks to help reduce adverse effects
107
are drug holidays good for on-off phenomenon
it can help for some people
108
what happens with abrupt cessation of levodopa
severe akinesia
109
what happens if you do drug holiday then start again with a low dose
there will be fewer averse effects than before
110
how long do the benefits of drug holidays last
not long
111
what 3 benefits of using DA agonists
- they dont have potentially toxic metabolites
- they do not compete with other substances for transporters
- they are receptor selective
112
how do you use dopamine agonists in treatment
with adjuct to levodopa/carbidopa, or to gradually replace to levodopa
113
what are 2 examples of dopamine agonists
bromocriptine and pergolide
114
which receptor does bromocriptine bind
agonist at D2
115
which receptor does pergolide bind
mixed D1 and D2 agonist
116
is pergolide or bromocriptine better
pergolide
117
what do bromocriptine and pergolide do to the required dose of levodopa
lower
118
what are the adverse effects of bromocriptine and pergolide
similar to levodopa but less sever (but mental symptoms are worse)
119
which dopamine agonists are the ergot derivatives
bromocriptine and pergolide (older ones)
120
which dopamine agonists are the older drugs
bromocriptine and pergolide
121
which dopamine agonists are the newer drugs
pramipexole and ropinirole
122
why are bromocriptine and pergolide able to stick around longer
because they are not shaped like a.a. unlike levodopa
123
how are pramipexole and ropinirole used in parkinsons therapy
they can be prescribed alone
124
how are bromocriptine and pergolide used in therapy
often given with levodopa
125
which DA receptors does pramipexole bind
D3 (D2 class) agonist
126
which DA receptors does ropinirole bind
pure D2 agonist
127
what are the adverse effects like for pramipexole and ropinirole
similar to levodopa
128
what are 2 benefits of using pramipexole
effective in advances parkinsons
| possible neuroprotective effect
129
what does MAO B metabolize
dopamine
130
what is selegiline do
blocks MAO B
131
when is selegiline used in treatment and how
with levodopa when its effects start declining
132
what are some contraindications for selegiline
patients that use TCAs or SSRIs
133
what does COMT do
metabolizes levodopa
134
what happens to COMT levels with more DDC inhibition
increase levels
135
which drug may also have antioxidant antiapoptotic effects in animals
selegiline (dont worry if dont know)
136
what are 2 examples of COMT inhibitors
tolcapone and entacapone
137
where does tolcapone act
centrally and peripheral (hepatotoxic)
138
where does entacapone act
only peripherally
139
what are some side effects of tolcapone and entacapone +1 really bad one
similar to levodopa, diarrhea, orange urine, orthostatic hypotension
tolcapone is hepatotoxic
140
which of tolcapone and entacapone is hepatotoxic
tolcapone
141
how does tolcapone and entacapone reduce the amount of levodopa needed
(COMT inhibitors)
increases its half life
increases levels of 3OMD which competes for transporters taking levodopa into blood (?idk)
142
what is amantadine
antiviral
143
how does amantadine work
blocks NMDA receptor on cholinergic neurons, may increase release brain dopamine
144
what are some bad things about using amantadine in parkinsons
it has lots of adverse effects
145
when are using anticholinergics the best for parkinsons
when the tremor is the main symptoms
146
when are using anticholinergics not great for parkinsons
if its rigidity or bradykineasia
147
why can anticholinergics be good for parkinsons
because a lack of DA release means overbalance of cholinergic excitation in the basal ganglia
