Parkinson's Disease Flashcards
1
Q
Cardinal symptoms of PD
A
- Tremor at rest
- Rigidity (muscular)
- Akinesia/bradykinesia - slowness and poverty of movement
- Postural instability
2
Q
Diagnosis of PD
A
At least 2 out of 3 of TRA
3
Q
Idiopathic PD features at initial presentation
A
- Asymmetric
- Positive response to levodopa or apomorphine
- Postural instability (& falls) NOT present
- Less rapid progression
- Autonomic dysfunction NOT present
- Neuroimaging (???????)
- Impaired olfaction (?)
4
Q
What tools are used to measure disease progression?
A
Hoehn and Yahr Staging
Unified Parkinson’s disease Rating Scale (UPDRS)
5
Q
Hoehn and Yahr Stage 1
A
Unilateral involvement
6
Q
Hoehn and Yahr Stage 2
A
Bilateral symptoms; NO balance impairment
7
Q
Hoehn and Yahr Stage 3
A
Impaired postural reflexes; physically independent
8
Q
Hoehn and Yahr Stage 4
A
Severe disability, yet able to walk or stand unassisted
9
Q
Hoehn and Yahr Stage 5
A
Wheelchair bound or bedridden
10
Q
UPDRS (1)
A
Mentation, behaviour, mood
11
Q
UPDRS (2)
A
Activities of daily living
12
Q
UPDRS (3)
A
Motor examination
13
Q
UPDRS (5)
A
Complications of Therapy
14
Q
MDS-UPDRS (1)
A
Non-motor Experiences of Daily living
15
Q
MDS-UPDRS (2)
A
Motor experiences of daily living
16
Q
MDS-UPDRS (3)
A
Motor examination
17
Q
MDS-UPDRS (4)
A
Motor complications
18
Q
Non-motor symptoms
A
- Dementia
- Depression
- Psychosis
- Sleep disorder
- Constipation
- GI motility
- Orthostatic hypotension
- Sialorrhoea
- Fatigue
19
Q
Early onset PD has ____ disease progression
A
Slower
20
Q
Early onset PD has less ______
A
Cognitive decline
21
Q
Early onset PD has earlier ________
A
Motor complications
22
Q
What is the common initial presentation of early onset PD?
A
Dystonia (involuntary muscle contractions that cause slow repetitive movements or abnormal postures that can sometimes be painful)
23
Q
Drug preference for early onset PD
A
Dopamine agonist > levodopa
24
Q
Does dopamine pass through BBB?
A
NO
25
Does L-DOPA pass through BBB?
Yes
26
What is the precursor of L-DOPA?
L-tyrosine
27
How is L-DOPA formed?
Hydroxylation by tyrosine hydroxylase (from L-tyrosine)
28
What is the precursor of dopamine?
L-DOPA
29
How is dopamine formed?
Decarboxylation by AADC (from L-DOPA)
30
What is dopamine broken down into?
1. DOPAC (by MAO)
2. 3-O-M-DOPA (by COMT)
31
Short term side effects of Levodopa
N/V, postural hypotension
32
Which symptoms is Levodopa best for?
Rigidity
Bradykinesia
33
Bioavailability of Levodopa
~33%
34
Levodopa is transported by ______.
Active saturable carrier system
35
Levodopa's absorption decreases with _____.
High fat & protein meal
36
What can be combined with Levodopa to enhance therapeutic effects?
DOPA decarboxylase inhibitors (DCI)
37
Levodopa:DCI
1:4 (sinement, madopar)
1:10 (sinemet)
38
Dose required daily to saturate DOPA decarboxylase
75-100mg
39
Motor complications of Levodopa
1. On-off
2. Wearing off (modify time of administration or switch to modified release at appropriate times)
3. Dyskinesia (add Amantadine & switch to modified released Levodopa)
40
What is useful for reducing stiffness on walking?
Sinemet SR
Madopar HBS
41
Administration instruction for Sinemet SR
Do not crush
42
Administration instruction for Madopar HBS
Do not open capsule
43
Dose adjustment when switching from IR to CR Levodopa/DCI
Increase dose
44
Dose adjustment when switching from CR to IR Levodopa/DCI
Decrease dose
45
Levodopa DDI (1)
Pyridoxine
- Cofactor of DOPA decarboxylase, generally not a problem if administer with DCI
46
Levodopa DDI (2)
Iron
Affect Levodopa absorption - space out administration
47
Levodopa DDI (3)
Protein
Affect Levodopa absorption - space out administration
48
Levodopa DDI (4)
Dopamine antagonists
- Metoclopramide, prochlorperazine (use domperidone for PD)
- SGA
- Risperidone
49
MOA of dopamine agonist
Acts on D2 receptors
Mimic action of dopamine
50
Examples of dopamine agonists
Pramipexole
Pergolide
Ropinirole
51
Is Pramipexole ergot derived?
No
52
Is Pergolide ergot derived?
Yes
53
Is Ropinirole ergot derived?
No
54
Dopamine agonists are preferred in ____ patients because_____.
Younger
Prevent or delay onset of motor complications
55
Dopamine agonists have less ________ than levodopa.
Motor complications
56
Common side effects of dopamine agonists
N/V, orthostatic hypotension, headache, dizziness and cardiac arrthymia
57
Side effects of ergot-derived dopamine agonists
Peritoneal fibrosis
Cardiac valve regurgitation
58
Side effects of no-ergot derived dopamine agonists
Sedation
Hallucinations
Somnolence
Daytime sleepiness
59
Dopamine agonists have ____ half-life and duration of action than Levodopa.
Longer
60
pK of Ropinirole
Mainly metabolised by liver (to inactive metabolites)
61
pK of Pramipexole
Excreted largely unchanged in urine
62
Pergolide is ____ registered in Singapore!
NOT
63
Pramipexole & Ropinirole are available in ___ & ___ form.
IR
SR
64
Neupro patches - active ingredient? available in SG?
Rotigotine
Exemption item
65
MOA of MAO inhibitors
Inhibit breakdown of dopamine
66
MAO-A
Peripheral, 5HT, NE
67
MAO-B
Central, DA
68
MAO inhibitors for PD
Selegiline
Rasagiline
69
Selegiline & Rasagiline are selective for MAO-_?
MAO-B (but not totally selective)
70
Selegiline is suitable for ___ stage of PD, and used as ____therapy.
Early
Monotherapy
71
Dose of Selegiline in PD
5mg OM to BD (2nd dose in the afternoon)
72
pK of Selegiline
Hepatically metabolised to amphetamines, which are stimulating
73
MAO-Bi side effects
Heartburn, loss of appetite
Anxiety, palpitation, insomnia
Nightmares, visual hallucination
74
DDIs of MAO-Bi
SSRIs, SNRIs, TCAs - washout recommended!
75
Food interactions with MAO-Bi
Tyrosine! (metabolised by both MAO-A and MAO-B)
76
MOA of COMT inhibitors
Inhibit dopamine breakdown
Major metaboliser of levodopa in the absence of DCI
77
Benefits of COMT inhibitors
Increases duration of each dose of levodopa, beneficial in decreasing "wearing off" responses
78
COMT inhibitors place in therapy
Used as adjunct to levodopa or levodopa/DCI
79
COMT inhibitors used in PD
Entacapone
Tolcapone
80
Important counselling point with Entacapone
Will cause diarrhoea, urine discolouration (orange)
81
Entacapone is a _____, _____ inhibitor.
Selective, reversible
82
Entacapone may cause ____ upon initiation, requiring ___________.
Dyskinesia
Decrease dose of levodopa
83
MOA of NMDA antagonist
Binds directly to the glutamate site of the NMDA receptor to inhibit the action of glutamate
84
MOA of Amantadine
a. Enhance release of stored dopamine
b. Inhibit presynaptic uptake of catecholamine
c. Dopamine receptor agonist
c. NMDA receptor antagonist
85
NMDA antagonist place in therapy in PD
Adjunctive to levodopa
86
Anticholinergic used in PD
Trihexyphenidyl
87
Advantages of anticholinergics
May be effective in controlling tremor
Peripherally acting agents may be useful in treating sialorrhoea
