PD Flashcards
(128 cards)
1
Q
What is the pathophysiology of parkinson’s?
A
Loss of SNc dopamine neurons
Increase of striatal cholinergic interneuron activity
Lewy bodies
Oxidative stress
2
Q
What is the clinical presentation of PD?
A
Slow and progressive (sx onset is associated with degree of neuronal loss and spread of Lewy bodies through certain parts of the brain)
3
Q
What are the cardinal features of PD?
A
Bradykinesia
Resting tremor (pill rolling/hands predominate)
Muscle rigidity
Gait dysfunction, postural instability - occurs later in disease
4
Q
What are the motor sx of PD?
A
Decreased dexterity Diminished arm swing when walking Dysarthria Dysphagia Shuffling gait Festinating gait Flexed posture "freezing" at initiation of movement Hypomimia (reduced facial animation) Hypophonia Micrographia Slow turning
5
Q
What are the autonomic sx of PD?
A
Bladder and sphincter disturbances Consitpation Diaphoresis Orthostatic BP changes Paroxysmal flushing Sexual disturbances Sialorrhea
6
Q
What are the mental status changes in PD?
A
Anxiety Depression Bradyphrenia (slow thought) Confused state Dementia Hallucinations/psychosis Sleep disturbance
7
Q
What are other sx in PD?
A
Fatigability Oily skin Pedal edema Seborrhea Weight loss
8
Q
What are the goals for PD treatment?
A
Manage motor/non-motor sx so patients can maintain QOL.
Preserve ability to perform ADLs, improve mobility, minimize AEs or treatment complications.
9
Q
When is treatment initiated in patients with PD?
A
When sx start to interfere with activities of daily living, employment, or WOL
10
Q
What leads to cholinergic activity?
A
Decline in dopaminergic neurons/activity to increase in cholinergic activity
11
Q
What is considered the most effective PD therapy?
A
Levodopa
12
Q
What are limitations to levodopa?
A
Motor fluctuations
Dyskinesia
Neuropsychiatric complications
Often debilitating and difficult to manage
13
Q
What may be initiate for mild-moderate PD?
A
Rasagiline or DAs (better SEs)
14
Q
What is the drawback to starting MAOIs or DAs for mild-moderate PD?
A
Expensive
Less effective
15
Q
What components of PD are not treated?
A
Freezing
Falling
Dementia
16
Q
What therapy has been studied and shows benefit in PD?
A
Exercise
17
Q
What are non-pharm interventions for PD?
A
Nutrition
Exercise
18
Q
What are PD patients at an increased risk for when it comes to nutrition?
A
Poor nutrition
Weight loss
Loss of muscle mass
19
Q
What are nutrition interventions for PD?
A
Encourage fluid and fiber intake to prevent/treat constipation
Adequate Ca intake for bone health
Take levodopa on empty stomach 1 hour before or after meals
20
Q
What is L-dopa the precursor of?
A
Dopamine
21
Q
Why do we give L-dopa and not dopamine for PD?
A
L-dopa crosses the BBB
22
Q
Where is L-dopa converted?
A
Centrally - results in efficacy
23
Q
What is the MOA of L-dopa?
A
Converted to dopamine by L-amino acid decarboxylase (L-AAD)
24
Q
What are the most effective medications from least to most?
A
Anticholinergics/amantadine
COMTi/MAOIs
DA
Levodopa/carbidopa
25
What causes AE from levodopa?
Resulting from peripheral conversion of levodopa to dopamine by L-AAD
26
What are the AEs of levodopa alone?
N/V
Cardiac arrhythmias
Postural hypotension
27
What AE is associated with end-of-dose "wear off" of levodopa?
Motor complications
28
What class is carbidopa in?
Decarboxylase inhibitor
29
What is the starting L-dopa dose for relief of disability?
200-300 mg/d
30
What is the upper range of L-dopa doses for severe parkinsonism?
800-1000mg/d
31
Is there a hard max dose of L-dopa?
No
32
What dose of carbidopa is needed to prevent peripheral AEs of L-dopa?
75mg/d
33
What is the max dose of carbidopa?
200mg/d
34
What is peak plasma concentration for L-dopa variability usually attributed to?
Erratic gastric emptying
35
What can affect gastric emptying?
Meals delay
| Antacids promote
36
Where is L-dopa primarily absorbed?
Duodenum
37
Is L-dopa protein bound?
No
38
What is the elimination 1/2 life for L-dopa alone?
1 hour
39
What is the elimination 1/2 life of L-dopa/carbidopa?
1.5 hours
40
What is the elimination 1/2 life of L-dopa/carbidopa + COMTi?
2-2.5 hours
41
Why do we increase the dose of controlled and extended release sinemet?
Not absorbed well?
42
Do we start with controlled or immediate release sinemet?
Immediate
43
Why would we switch to controlled release sinemet?
Motor sx
44
Will all patients eventually receive sinemet?
Yes
45
What formulations does L-dopa/carbidopa come as for use in feeding tubes?
Gel (Duopa)
46
What are the non-ergot derivative DAs?
Pramipexole
Ropinirole
Rotigotine (transdermal patch)
47
What are the AEs of DAs?
```
N/V
Sedation
Imuple control disorders (gambling, pathologic shopping etc)
Daytime sedation including:
Sleep attacks
Lightheadedness & postural hypotension
Hallucinations
Vivid dreams
Confusion
```
48
What is the ergot derivative DA?
Bromocriptine
49
Which DA requires renal dose adjustment?
Pramipexole
50
Why is bromocriptine no longer used?
Increased risk of pulmonary fibrosis
| Lower efficacy compared to other DAs
51
How long do most patients use DA monotherapy?
A few years before requiring L-dopa
52
When are DAs used as L-dopa adjunct therapy?
With a deteriorating response to L-dopa
Experiencing fluctuations in L-dopa response
Experiencing motor fluctuations
53
What do DAs reduce the frequency of?
"off" epsiodes
54
What drug class produces a levodopa sparing affect?
DA
55
What is apomorphine?
Short acting injectable used for acute, intermittent treatment of "off" episodes of PD in patients already receiving levodopa therapy
56
Where is apomorphine given?
Setting where BP can be monitored continuously
57
What apoprophine dose do we give first?
a 0.2mL (2mg) test dose
58
How often do we monitor the apomorphine test dose?
Monitor supine and standing BP predose, 20, 40, 60 minutes postdose
59
If apomorphine is tolerated, how do we titrate?
Begin with 0.2mL as needed, and increase by 0.1mL if necessary
60
What do we do if the first apomorphine dose is ineffective?
Do not redose
61
What are AEs of apomorphine?
```
N/V --> severe
Hypotension
Injection site reactions
Dyskinesia
Hallucinations
```
62
How do we prophylax for apomorphine n/v?
Trimethobenzamide (antiemetic) should be initiated 3 days before test dose and continue for at least 2 months
63
What is the MOA of MAOIs?
Irreversible selective MAOI that block dopamine breakdown and can modestly extend the duration of action of levodopa
64
How long can MAOIs extend levodopa duration of action?
Up to 1 hour of "on" time during the day
65
What do MAOIs decrease the formation of?
Free radicals (possible neuroprotective effect)
66
Which MAOI is approved for initial monotherapy or adjunct to levodopa for PD treatment?
Rasagiline
67
Which MAOI can be used as adjunctive treatment to levodopa for PD?
Selegiline
68
What are AEs of MAOIs?
```
Dyskinesia
Hallucinations
Delusions
Nausea
Orthostatic hypotension
```
69
What are DDIs for MAOIs?
MAO-B receptors have less than MAO-A receptors
70
How is rasagiline administered?
Once daily
71
How is rasagiline metabolized?
To relatively inactive metabolite and is devoid of amphetamine like side effects
72
How is selegiline metabolized?
Metabolites are amphetamine type and can cause insomnia and jitteriness (negates theorized neuroprotective effect)
73
What is the brand of levodopa/carbidopa/entacapone?
Stalevo
74
What is Entacapone dosing?
200mg with each levodopa/carbidopa dose
75
What is the max number of entacapone doses per day?
8
76
What is the class for entacapone?
COMT-inhibitors (catechol-O-methyl transferase inhibitors)
77
What is the MOA of COMT-i?
Prevent conversion of levodopa to its metabolite 3-O-methyldopa (3OMD), thuse extending the effects of each levodopa dose
78
Can entacapone be used alone?
No, only effect when used with levodopa
79
What is entacapone used for?
Managing motor fluctuations
80
Where does entacapone work?
Inhibits COMT in periphery only
81
What are the AEs of entacapone?
```
Dyskinesia
Hallucinations
Confusion
Nausea
Orthostatic hypotension
Brownish-orange urine discoloration
```
82
What are the SE of tolcapone?
Severe and fatal hepatotoxicity
Strict liver monitoring required
Must sign a consent form
83
When would patients take tolcapone?
Not responding to entacapone
84
What drugs are anticholinergic?
Benztropine
| Trihexyphenidyl
85
Where do the anticholinergics work?
Centrally
86
What are anticholinergic MOA?
Blocks excessive cholinergic activity involved in PD pathology in the CNS at muscarinic sites
87
What PD features do anticholinergics not treat?
Bradykinesia
| Gait disturbances
88
What PD feature might anticholinergics help with?
Dystonia
89
What is the efficacy of anticholinergics in PD?
Tremor is similar to DA
90
What are the AEs of anticholinergics?
```
Blurred vision
Confusion
Constipation
Dry mouth
Memory difficulty
Sedation
Urinary retention
```
91
What is the limiting factor for anticholinergics?
Can try to reduce dose but may need to continue
92
What is the ideal patient for anticholinergic therapy?
Younger and cognitively intact
| Can be used with other therapies for PD
93
What is an NMDA receptor antagonist?
Amantadine
94
What is NMDA mainly used for/?
tremor
95
What is NMDA somewhat effective for?
Rigidity and bradykinesia
96
What is amantadine effective in suppressing?
Levodopa induced dyskinesia
97
What are the AEs for amantadine
Confusion in elderly at HD
Sedation and vivid dreams
Dry mouth
Livedo reticularis (diffuse mottling of the skin)
Hallucinations
Rare SE include depression, anxiety, dizziness, psychosis, and confusion
98
How is amantadine adjusted?
Renally
99
Which PD drug is best used for short term monotherapy?
Amantadine d/t tansient modest efficacy
100
What is the brand and dose of benztropine?
Congentin 0.5-0.4 1-2x/d
101
What are the brands and doses of carbidopa/levodopa?
Sinemet 2-6x/d 300-1000
Sinemet CR 3-6x/d 400-1000
Rytary (ER) 3-5x/d 435-1170
102
What are the brands and doses of DAs?
Pramipexole (Mirapex ER) 1.5-4.5 TID
Ropinorole (Requip) 8-24 TID
Rotigotine (Neuro patch) 2-8 Daily
103
What is the brand and dose of entacapone?
Comtan 200-1600 w/levodopa
104
What are the brands and doses of MAO-B inhibitors
Rasagiline (Azilect) 0.5-1 daily
| Selegiline (Eldepryl) 5-10 BID
105
What is the brand and dose for amantadine?
Symmetrel 200-300 BID
106
What is the dose for stalevo?
600-1600 6-8 times daily
107
What is the brand and dose of pimavanserin?
Nuplazid 34 daily
108
If a patient has mild motor sx (any age) what is potential therapy options?
Consider rasagiline
Can add:
Amantadine
Anticholinergics (for tremor in younger, cognitively intact pts)
109
If a patient has mild/mod motor sx and is < 60yo w/no cognitive impairment, what are potential therapy options?
DA (initial therapy or addition to establish regimen)
110
If a patient has severe motor sx or is > 60yo or has cognitive impairment, what are potential therapy options?
Levodopa (inital therap or addition to established regimen)
111
How do we adjust levodopa therapy with motor fluctuations?
Increase dosing frequency
Add MAO-B or COMTi
Add DA
112
How do we adjust levodopa therapy if there is peak dose dyskinesia?
Reduce dopaminergic dose
| Add amantadine
113
What is the wearing off period of levodopa?
End of dose deterioration
114
What are the possible treatments for wearing off?
Increase frequency of doses
Change to CR/ER formulation
Add DA, MAOI, COMTi, amantadine
SQ apomorphine
115
What can cause drug-resistant off periods?
Delayed gastric emptying or absorption
116
What are possible treatments of drug-resistant off periods?
```
Give on empty stomach
Crush/chew and take on full glass of water
Avoid CD form; ER may be ok
Switch to ODT formula
Increase dose and/or frequency
```
117
What is the treatment of rapid fluctuations?
Add DA, MAOI, COMTi that decrease clearance of levodopa
| Drug free period/drug holiday
118
What are treatments of nocturnal off states and dystonia?
Bedtime dose of DA
| ER form of levodopa or DA
119
What is treatment of dystonia?
Baclofen/botox
120
What are possible treatments for dykinesia?
Smaller, more frequent doses of levodopa
Use of sustained release product
Amantadine 200-400mg/d
121
What drugs may worsen dyskinesia?
DA, COMTi, MAOI
122
What is used to treat depression in PD?
Pramipexole
Consider MAOI as they are derived from antidepressants
TCA may be more effective than paroxetine/placebo
123
How do we treat dementia in PD?
Cholinesterase inhibitors
124
What are the preferred APXs for disruptive psychotic sx?
Pimavanserin
Quetiapine
Clozapine
125
What is pimavanserin?
SGA indicated for PD suffering with hallucinations and delusions
126
What is the MOA of pimavanserin?
Combined inverse agonist/antagonist at serotonin receptors; does not have affinity for dopamine receptors
127
How is quetiapine used in PD hallucinations?
Bedtime dose at first, low dose, gradually increase weekly if needed
128
What does clozapine work on in PD?
Motor sx and hallucinations
