Exam 2: Parkinson's Flashcards
(84 cards)
1
Q
Parkisonism vs. Parkinson’s
A
Parkinsonism: disorder presenting with classic s/s, usually secondary to some other factor
Parkinson’s disease: no known secondary cause
2
Q
Istradefylline (Nourianz) AE
A
dyskinesia
insomnia
hallucinationss
dizziness
3
Q
Istradefylline (Nourianz) DDI
A
- strong cyp3A4 inhibitors → take 20mg
- avoid if using strong CYP3A4 inducers
- also CYP1a1
4
Q
Istradefylline (Nourianz) MOA
A
adenosine A2A recceptor antag
use in combo with carb/levo for off episodes
5
Q
Istradefylline (Nourianz) dosing
A
20mg QAM to MDD of 40
- higher dose needed if pt smokes 20+ cigarettes a day
- 20mg QD if Child-Pugh Class B
6
Q
Amantadine AE
A
orthostatic hypotension, dizziness, falls
hallucinations
sedation
anticholinergic AE
Livedo reticularis - mottling of skin with LE edema
NMS with abrupt d/c
7
Q
Amantadine DDI
A
- LIVE flu vaccine (less effective)
- quinine/quinidine
- HCTZ/triamterene
8
Q
Amantadine agents and dosing
A
Symmetrel IR
- 300mg/day in divided doses
Gocovri ER
- start 137 mg, increase to 274mg after 1W
Osmolex ER
- start 129mg, increase to 322 after 1W
9
Q
Apomorphine (Apokyn) AE
A
- N/V
- dizziness, sommnolence, yawning
- chest pain, pressure
- dyskinesia
- falls
- rhinorrhea
10
Q
Rotigotine (Neupro) AE
A
- CNS
- GI
- peripheral edema
- application site
- Sodium metabisulfite allergy
11
Q
Apomorphine (Apokyn) DDI
A
- 5HT3 antags increase hypotensive effects CI
- QTc prolonging agents may have additive effects
- Dopamine antags may decrease effectivenes
12
Q
Pramipexole DDI
A
inhibitors of renal tubular secretion (cimetidine)
13
Q
Ropinirole DDI
A
Ropinirole is a CYP1A2 substrate
- Inhibitors of CYP1A2
- cimetidine
- cipro
- macrolide abx
- omeprazole
- Inducers of CYP1A2
- CBZ
- phenobarbital
- phenytoin
- rifampin
14
Q
Rotigotine (Neupro) DDI
A
dopamine antags
- APS
- metoclopramide
15
Q
Ropinirole CI
A
- abrupt d/c
- hepatic disease
16
Q
Apomorphine (Apokyn) dosing and admin
A
- 2mg SC under medical supervision
- Monitor bp pre-dose, and Q20min for an hour post dose
- Can increase by 1mg every few days to max of 6mg
- do NOT exceed TID dosing
- rotate injection sites
- can pre-treat with antiemetic (Tigan- trimethobenzamide hydrochloride)
17
Q
Pramipexole dosing
A
- IR: 0.125 mg TID; MDD of 1.5 mg TID
- ER: 0.375 mg QD; MDD of 4.5 mg QD
18
Q
Ropinirole dosing
A
- IR: 0.25 mg TID; MDD of 24 mg
- XL: 2 mg QD; MDD of 24 mg
19
Q
Rotigotine (Neupro) dosing
A
patch - start 2mg/24 hours, increase QW by 2 mg up to 6 mg
4 mg = minimum effective dose.
20
Q
Selegiline AE
A
- CNS
- GI
- HTN crisis
- Serotonin syndrome
- insomnia, jitteriness
- HA
- Irritation of buccal mucosa (zelapar)
21
Q
Rasagiline (Azilect) AE
A
Monotherapy
- HA
- Arthralgia
- GI upset
- Falls
WIth levodopa
- dyskinesia
- weight loss
- orthostasis
22
Q
Safinamide (Xadago) AE
A
dopaminergic
- Dyskinesia
- hallucinations/psychosis
- Impulse control
- Daytime somnolence
- NMS with abrupt withdrawal
- retinal pathology
23
Q
Selegiline DDI
A
- non-selective MAOI
- TCAs, SSRI, SNRI, DXM - serotonin syndrome
- tyramine containing foods at doses >10mg
- sympathomimetics
24
Q
Rasagiline (Azilect) DDI
A
- non-selective MAOI, needs a 2 week washout
- metabolized CYP1A2 (cipro)
- TCAs, fluoxetine, needs a 5 week washout
- sympathomimetics
25
Safinamide (Xadago) DDI
- serotonergic drugs: opioids, SSRI, SNRI, TCA, cyclobenzaprine, methylphenidate, amphetamines, St. John’s wort
- DXM (bizzare behavior)
- BCRP substrates
26
Selegline CI
not absolute contraindications
- dementia, severe psychosis
- meperidine, tramadol, methadone, propoxyphene
27
Rasagiline (Azilect) CI
meperidine, tramadol, methadone, propoxyphene, mirtazapine, cyclobenzaprine, DXM, St. John wort
vasoconstrictors (d/t potential for HTN crisis)
28
Safinamide (Xadago) CI
Child-Pugh class C
29
Selegeline MOA
- Non-competitive, *selective* antag of MAO-B → decrases breakdown of DA
- Decerase free radical production
30
Rasagiline (Azilect) MOA
- Non-competitive, *selective* antag of MAO-B → decrases breakdown of DA
- Decerase free radical production
31
Safinamide (Xadago) MOA
Na and K blocker → decrease glutamate release
32
Selegiline dosing
- 5mg QD or BID
- Zelepar - ODT 1.25mg (2.5mg after 2 weeks)
33
Rasagiline (Azilect) dosing
- 0.5 mg with levodopa
- 1.0 mg monotherapy
34
Safinamide (Xadago) dosing
- start 50mg QD, increase to 100mg Q2W
- If some hepatic impairment, MDD 50mg
35
Tolcapone dosing
100mg TID
36
Tolcapone AE
hepatocellular injury (incrase in LFTs, monitor)
CI in pts with exiting hepatocellular disease
37
Opicapoine (Ongentys) AE
similar to levodopa and other COMT inhibitors
38
Entacapone AE
similar to levodopa + urine discoloration (brown/orange)
39
COMT inhibitor (class) DDI
Drugs metabolized by COMT
non-selective MAOIs
40
Opicapone (Ongentys) CI
catecholamine secreting neoplasm
non-selective MAOIs
41
COMT inhibitor (class) MOA
Reversible, selective inhibitor of COMT, prevent breakdown of L-dopa and extend L-dopa’s effects
NO EFFECT IN ABSENCE OF L-DOPA
42
Levodopa AE
dyskinesia (choreiform and dystonic reacion)
on-off phenomenon; decrased effectiveness over time
psychatric disturbances/vivid dreams
GI effects
orthostatic hypotension
saliva, sweat, or urine discolration
neuroleptic malignant syndrome w abrupt d/c
43
Levodopa DDI
- DA antags (metoclopramide, antipsychotics)
- non-selective MAOIs → toxic effects
- pyridoxine (if dose >200mg) redcues efficacy of levo → moitor
- high protein intake → separate admin by 2hrs
- iron salts → separate admin by 2hrs
44
Levodopa CI
- brastfeeding
- closed angle glaucoma
- preggers (d/t carbidopa)
- non-selective MAOI (within 2 weeks of Inbrija only)
45
Levodopa PKPD
Large amino acid transporter in GI and BBB
95% metabolized by LAAD into DA
<1% reaches CNS without a decarboxylase inhibitor (carbidopa - inhibits peripheral L-dopa metabolism)
Renally eliminated
46
Levodopa PO dosing
Carb
- carbidopa dose usually 70-100mg/day
Levo
- start 200-300mg/day in divided doses
- increase by no more than 100 mg/week
- avoid >1000mg/day d/t AE
47
Levodopa MOA
Precursor to DA
Crosses BBB when DA does not
48
Available agents containing levodopa
PO IR
PO ER
Carb/Levo/Entacapone (Comtan)
intestenal gel (Duopa)
powder inhalation I(nbrija)
49
Levodopa IR vs ER
IR: 30 min onset, ER is 2 hrs
if switching from IR to ER half the dosing frequency
ER has a lower F
ER decrease the off time
50
Duopa
intestinal gel levodopa
infused by wearable pump through PEG-J to bypass GI absorption → more consistent L-dopa levels
must be switched from IR tabs
MDD 2000mg
risk of bleeding and infection
51
Inbrija
powder inhalation levodopa
does NOT replace PO meds
inhale 2mg PRN for off symptoms
respiratory AE (don’t use in pts with lung diseases)
52
Anticholinergic AE
blind as a bat (mydraisis)
dry as a bone (dry mouth, constipation)
hot as a hare (fever)
mad as a hatter (depressioin, agitation)
red as a beat (flushed)
53
Parkinson’s anticholinergic agents and dosing
Benztropine
- start 0.5-1 mg/day; MDD 6mg/day
Trihexyphenidyl
- start 1-2mg/day; MDD 15mg/day
54
Which Parkinson’s med MAY slow down progression of the disease and not just provide symptom treatment?
Rasagiline
55
Parkinson’s primary s/s
- Bradykinesia
- Postural instability
- Resting tremor
- Rigidity
56
Parkinson's motor s/s
- Decreased dexterit
- Dysarthria
- Freezing at initiation of movement
- Slow turning
57
Parkinson's autonomic s/s
- Bladder and anal sphincter disturbances
- Constipation
- Diaphoresis
58
Parkinson's mental status changes
- Confusion
- Dementia
- Psychosis
59
Parkinson’s dx
bradykinesia + one of the following
- Limb muscle rigidity
- Resting tremor
- Postural instability
60
bradykinesia
slowness and difficulty iniating voluntary movement
Initially distal muscles, eventually all
facial masking - lack of facial expression
motor acts become difficult, especially with repetitive motions
“freezing”
61
Things that could cause parkinsonism (not parkinson's disease)
- First gen antipsychotics
- Prochlorperazine and metoclopramide
- Neurogenerative conditions
- Strokes
- Toxins
62
Parkinson's patho
state of DA deficiency
functional imbalance between DA and ACh
loss of dopaminergic cells in substantia nigra
formation of lewy bodies in remaining SNc neurons
potentially: overactivation of adenosine A2A receptor can cause inhibition of motor function
63
Stages of levodopa on/off and management
On/Off : d/t DA neurons dying off → lose ability to store DA → response time gets shorter and shorter
- Stage I: not aware of variation in effect
- Stage II: midafternoon loss of benefit, needs second dose
- Stage III: sleep benefit is lost, early morning akinesia appears
- Stage IV: regular “wearing off” Q4H, then response gradually shortens
- Stage V: “wearing off” from each dose and abrupt “off periods”
- May require dosing Q2H
64
Parkinson's motor complications
On-off response
off, no on
delayed onset
peak-effect dyskinesia
dystonia (muscle cramps)
freezing
65
Parkinson's non-motor complications
depression
dementia and cognitive impairment
insomnia
excessive daytime somnolence
orthostatic hypotension
sexual dysfunction
constipation
urinary frequency
drooling
psycosis
66
Managing on-off response options
switch to CR (decresed frequency)
add DA agonist, MAOI-B, COMT or amantadine
67
Managing off, no on response options
increase dose frequency and water intake
use ODT formuations
in advanced disease, APO SQ
68
managing delayed onset options (Parkinson’s)
take on empty stomach, with water, avoid protein
if on CR, add or switch to IR
69
managing peak-effect dyskinesia options
decrease dose, increase frequency
add amantadine
use CR or a DA agonist
70
managing dystonia options
take IR in early morning, use CR at nigh
consider switch to DA agonist, or adding baclofen, or botox
71
managing freezing options (Parkinson’s)
increase dose
add DA agonist
try non-pharm
72
managing depression (Parkinson’s)
pramipexole
SSRI
venlafaxine
TCAs
73
managing dementia and cognitive impairment
Ach inhibitors (rivastigie donepezil, galantamine)
74
Managing insomnia
eszopiclone
melatonin
75
managing excessive daytime somnolence
modafanil
76
managing orthostatic hypotension
fludrocortisone
midodrine
droxidopa (short term)
77
managing sexual dysfunction
sildenafil
78
managing constipation
PEG
probiotics
fiber
lubiprostone
79
managing urinary frequency
solifenacin
80
managing drooling
glycopyrrolate
botox
81
managing psychosis in Parkinson’s
1. Evaluate hypoxemia, infection, electrolyte distrubnace, *esp if abrupt chnge in mental status*
2. Simply regimen: d/c meds withh highest risk:benefit ratio
- Anticholinergics
- Taper and d/c amantadine (abrupt withdrawal can cause delirium)
- Selegiline
- Taper and d/c DA agonists
- consdier decreaseing L-Dopa and d/c’ing COMT
3. Consider atypical antipsychotic drugs
- Seroquel: 23.5-50mg QHS, increase QW
- Clozapine: 12.5-50mg QHS, increase QW (monitor neutrophils)
- Pimavanserin tartrate (Nuplazid) 17mg G2T QD
82
Pimvavanserin tartrate (Nuplazid) MOA
5HT2A/2C inverse agonist (no action at DA recceptor)
83
Pimvavanserin tartrate (Nuplazid) BBW
increased death in elderly pts with dementia
84
Pimvavanserin tartrate (Nuplazid) AE
QTc prolongation, peripheral edema, nausea, confusion
