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PHAR358 > Parkinsons Disease > Flashcards

Parkinsons Disease Flashcards

1
Q

What are 3 words to describe Parkinsons?

A

chronic
progressive
neurodegenerative

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2
Q

What is the most common movement disorder?

A

Parkinsons

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3
Q

Describe the pathophysiology of Parkinsons.

A

caused by progressive death of dopamine-producing neurons in the substantia nigra (part of the basal ganglia)
-death of DA neurons = messages telling the body how and when to move are delivered slowly or incompletely
-individual is unable to initiate and control movements in a normal way

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4
Q

What is the role of dopamine in movement?

A

important for smooth, coordinated, controlled movements

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5
Q

What is the etiology of Parkinsons?

A

unknown
some decline of dopaminergic neurons occurs with aging
-Parkinsons is an acceleration of that process

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5
Q

What are the two components of the substantia nigra?

A

pars compacta: DA producing
pars reticulata: GABA neurons

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6
Q

What are the risk factors for Parkinsons?

A

family history
pesticide exposure
repeated head injuries

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7
Q

What are the protective factors against Parkinsons?

A

smoking
high coffee consumption
intensive exercise

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8
Q

What are the hallmark movement symptoms of Parkinsons?

A

TRAP
-tremor
-rigidity
-akinesia/bradykinesia
-postural instability
3 S’s: slow, stiff, shaky

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9
Q

Describe the diagnosis of Parkinsons.

A

clinical diagnosis
Movement Disorder Society Clinical Diagnostic Criteria:
-must be present: bradykinesia
-at least 1 of: rest tremor or rigidity
-supportive: response to DA tx, levodopa-induced dyskinesias, olfactory loss

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10
Q

What is the takeaway regarding the presentation of Parkinsons?

A

a heterogenous disorder with substantial variations in clinical presentation

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11
Q

Describe the distinguishing features of Parkinsons.

A

tremor-predominant subtype:
-often younger patients
-typically have a slower, more benign course of progression
akinetic/rigid subtype:
-often have a more rapid rate of progression of motor sx
-particularly in older patients

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12
Q

What is the key feature of the other Parkinsonisms?

A

they do not respond to levodopa

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13
Q

What are some medications that can cause Parkinsonisms?

A

typical neuroleptics
atypical neuroleptics
-safer alts: clozapine, quetiapine
antinauseants/prokinetics
-safer alt: domperidone
miscellaneous: lithium, valproic acid

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14
Q

What are some “other” clinical features of Parkinsons?

A

often precede motor symptoms:
-hyposmia
-constipation
-depression
-fatigue
-REM Sleep Behavior Disorder
early in disease course:
-micrographia
-hypophonia
-dry eyes
-flat affect
later symptoms:
-sexual dysfunction
-sialorrhea
-autonomic dysfunction
-psychiatric disturbances (delusions/hallucinations)
-cognitive impairment and dementia

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15
Q

What are some principles of treatment for Parkinsons?

A

no PD treatment modifies disease progression
symptomatic treatment only
progressive - therefore ongoing medication changes and adjustments will be needed

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16
Q

What are the goals of therapy for Parkinsons?

A

reduce signs and symptoms of Parkinsons
minimize complications of drug therapy
maintain independence
improve/maintain QoL

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17
Q

What are the non-pharm treatments for Parkinsons?

A

physical therapy
occupational therapy
speech therapy
dental/vision/hearing care
psychological support
surgery

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18
Q

What are the classes of medications for Parkinsons?

A

levodopa
dopamine agonists
MAO-B inhibitors
amantadine
COMT inhibitors
anticholinergics

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19
Q

What does pharmacotherapy of Parkinsons focus on?

A

increasing dopamine levels (directly or indirectly)

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20
Q

What is the effective cornerstone of treatment for Parkinsons?

A

levodopa

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21
Q

What is levodopa always given with?

A

decarboxylase inhibitor
-carbidopa or benserazide

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22
Q

What is the role of carbidopa or benserazide when used with levodopa?

A

prevents conversion of levodopa to DA outside of the brain
-enhances efficacy
-reduces AE
neither carbidopa nor benserazide can cross the BBB

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23
Q

What is the MOA of levodopa?

A

crosses BBB –> converted to DA via decarboxylase

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24
Q

Describe the effectiveness of levodopa.

A

initially, universally effective for:
-bradykinesia
-rigidity
-respond in days, max 2 weeks
variable effect: tremor
less likely to help with:
-poor balance
-non motor sx

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25
Q

What can decrease the bioavailability of levocarb?

A

protein
iron
antacids

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26
Q

How should levocarb be initiated?

A

titrate slowly to prevent nausea/dizziness

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27
Q

How should levocarb be discontinued?

A

need to taper off slowly due to risk of NMS

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28
Q

Why is controlled release levocarb rarely used?

A

delayed and unpredictable onset
-rarely used apart from overnight

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29
Q

What are the adverse effects of levocarb?

A

nausea, stomach upset
dizziness/orthostasis
fatigue
vivid dreams
confusion/hallucinations (later stages)

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30
Q

What can occur with levodopa therapy after ~5 years of treatment?

A

wearing off (med not lasting as long as it used to)
on-off phenomena (fine one min, not fine the next min)
freezing
dyskinesias (abnormal, involuntary movements)
-due to increases sens of brain to levodopa as PD progresses
-commonly limbs and trunk
-common shortly after a dose

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31
Q

What are some of the new formulations of levodopa?

A

Duodopa (intestinal gel)
Vyalev (SQ infusion)
inhaled capsules
designed to address limitations of oral admin

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32
Q

How is Duodopa delivered?

A

enteral (PEG-J tube)
-delivers constant low doses

33
Q

What is the benefit of Duodopa?

A

reduces off time by 2h/day without increasing dyskinesias

34
Q

How is Vyalev delivered?

A

continuous subcut infusion
-delivers low and constant doses

35
Q

What are the adverse effects of Vyalev?

A

injection site rxns
dyskinesias
psychosis

36
Q

What is the use of the inhaled levodopa capsules?

A

prn for unexpected off-periods or delayed onset
-onset: 10 minutes
-duration: 1 hour

37
Q

What are examples of dopamine agonists?

A

ergot derivatives: bromocriptine, cabergoline
-basically never used due to CV + pulmonary toxicity
non-ergot derivates: pramipexole, ropinirole, rotigotine

38
Q

What is the MOA of dopamine agonists?

A

mimic the effects of DA by binding to post-synaptic DA receptors

39
Q

What is the place in therapy for dopamine agonists?

A

may be used as initial therapy in young pts (<60)
-“save” levodopa for later
not preferred in older adults due to poor tolerability
-may be used as add on once motor complications develop if refractory/intolerant to other options
used for restless legs syndrome (hs)

40
Q

How do dopamine agonists compare to levodopa in terms of efficacy and tolerability?

A

less effective for motor symptoms than levodopa
more side effects
less risk of motor complications seen with levodopa

41
Q

What are the adverse effects of dopamine agonists?

A

more common with levodopa:
-nausea/GI upset
-orthostatic hypotension
-confusion
-fatigue
-hallucinations
drowsiness, sudden sleep attacks
leg swelling
impulse control disorder - up to 15% of pts
-pathological gambling
-hypersexual behavior
-compulsive shopping
-DA dysregulation syndrome

42
Q

How should dopamine agonists be discontinued?

A

taper slowly –> NMS risk

43
Q

What is apomorphine?

A

very potent DA agonist used for rescue therapy (freezing)
-comes as injectable or SL

44
Q

What is the role of MAO?

A

enzyme that breaks down DA, other NTs, and amines
-MAO A: breaks down NE and 5HT preferentially
-MAO B: breaks down DA and other amines preferentially

45
Q

What are examples of MAO-B inhibitors?

A

rasagiline
selegiline

46
Q

When do MAO-B inhibitors lose their selectivity?

A

at 2-5x the recommended therapeutic dose
-no need to restrict dietary tyramine at doses used for PD

47
Q

What is the place in therapy for MAO-B inhibitors?

A

can be used as monotherapy if symptoms are mild
can be used later in disease course for motor complications with levodopa therapy (rasagiline)
-wearing off, freezing

48
Q

How do MAO-B inhibitors compare to levodopa in terms of efficacy and safety?

A

less effective than levodopa
fewer adverse effects and less frequent dosing

49
Q

What are the side effects of MAO-B inhibitors?

A

generally well tolerated
-nausea, headache, insomnia

50
Q

What is the risk of combining an MAO-B inhibitor with an SSRI/SNRI?

A

unlikely to cause serotonin syndrome at recommended doses
-lowest effective dose should be used
avoid DM in patients taking MAO-B inhibitors

51
Q

What is an example of a COMT inhibitor?

A

entacapone

52
Q

What is the MOA of entacapone?

A

blocks COMT in periphery = more levodopa gets to brain

53
Q

How should entacapone be given?

A

MUST be given with levodopa
-has no effect on its own
-used for prolonging the action of levodopa once motor complications develop (wearing off, freezing)

54
Q

What should be done to the dose of levodopa when entacapone is started?

A

decrease levodopa dose by 30%
-to minimize dyskinesia

55
Q

What are the adverse effects of entacapone?

A

nausea, diarrhea
may turn urine and sweat an orangey-brown colour

56
Q

What is the MOA of amantadine?

A

unclear in PD

57
Q

What is the role of amantadine?

A

limited to treating bothersome dyskinesia later in disease course

58
Q

What are the adverse effects of amantadine?

A

nausea, confusion, hallucinations, peripheral edema
livedo reticularis
not as well tolerated in older adults due to cognitive effects

59
Q

What are examples of anticholinergics?

A

trihexyphenidyl
benztropine
procyclidine

60
Q

What is the MOA of anticholinergics in Parkinsons?

A

decrease the amount of ACh in the brain to restore the DA/ACh balance in the striatum

61
Q

What is the role of anticholinergics in Parkinsons?

A

effective mainly for tremor
-not effective for other motor symptoms
not used often; poorly tolerated in older adults

62
Q

Do we always have to start pharmacotherapy at the initial diagnosis of Parkinsons?

A

no need to start if there is no functional impairment

63
Q

What are some steps we can take with levodopa itself when levodopa is failing?

A

take on an empty stomach as consistently as possible
add levocarb CR @ hs
wearing off: increase dosing frequency
dyskinesias: smaller, more frequent doses

64
Q

What are some agents we can add on when levodopa is failing?

A

dyskinesias:
-amantadine
wearing-off:
-COMT inhibitor, MAO-B inhibitor = decrease off-time by 1-1.5h/day
-dopamine agonist = decrease off-time by 2h/day

65
Q

What is the surgical treatment for Parkinsons?

A

deep brain stimulation

66
Q

What is an under treated aspect of Parkinsons?

A

non-motor symptoms
-can have a substantial impact on QoL

67
Q

What are examples of non-motor symptoms in Parkinsons?

A

constipation
depression
autonomic dysfunction (ED, orthostasis, incontinence)
hallucinations and delusions
drooling
sleep disorders

68
Q

Describe constipation management in Parkinsons.

A

usual lifestyle: increase fiber, fluid, and exercise
avoid constipating meds/OTCs
domperidone can be considered to increase GI motility
PEG considered 1st line for preventing and managing
-may need to add stimulant on top if insufficient

69
Q

Describe depression management in Parkinsons.

A

little evidence to guide depression management in PD
generally managed similarly to patients without PD
-bupropion not DOC due to additive dopaminergic effect
-sertraline/citalopram/venlafaxine/duloxetine safe + effective
re-evaluate need, deprescribe if possible
-increased fall and orthostasis risk

70
Q

What causes autonomic dysfunction in PD?

A

PD and PD drugs

71
Q

What should be some of the first steps in evaluating orthostatic hypotension in Parkinsons?

A

review antihypertensives
ensure adequate hydration
review other meds
stand slowly
compression stockings
increase salt intake

72
Q

When do we consider drugs for orthostatic hypotension in Parkinsons? What are the options?

A

severe and refractory
domperidone:
-least evidence of efficacy but no supine HTN
midodrine:
-alpha 1 agonist
-limited by supine HTN (take last dose >4h before bed)
fludricortisone:
-mineralocorticoid
-limited by supine HTN

73
Q

Describe urinary incontinence management in Parkinsons.

A

non-pharm preferred
-regular toileting
-assistive devices
-decrease caffeine intake
-decrease fluid intake in evening
pharmacotherapy if refractory

74
Q

Describe erectile dysfunction management in Parkinsons.

A

PDE5-inhibitors used 1st line
apomorphine injections may be helpful

75
Q

Describe sialorrhea management in Parkinsons.

A

chewing gum or soft candy can help trigger swallowing reflex
ipratropium spray to mouth
atropine eye drops given SL (usually tried first)
refractory or atropine AEs –> Botox

76
Q

Describe insomnia management in Parkinsons.

A

usual sleep hygiene measures
adequate control of PD motor symptoms at night
melatonin has some evidence of benefit
doxepin or trazodone if refractory

77
Q

What is REM Sleep Behavior Disorder?

A

loss of muscle atony during REM sleep
individuals act out dreams - violent and can cause injury
often predates diagnosis of PD

78
Q

Describe management of REM Sleep Disorder.

A

avoid hs dosing of ADs (may worsen sx)
if tx necessary:
-melatonin (limited evidence)
-clonazepam (best evidence)

79
Q

Describe management of restless legs syndrome in Parkinsons.

A

screen for iron deficiency
optimize dopaminergic therapy - consider hs DA agonist
2nd line: gabapentin, pregabalin

80
Q

Do all hallucinations require treatment in Parkinsons patients?

A

not all do
-if insight is preserved, infrequent, and not bothersome = pharmacotherapy not required

81
Q

Describe management of hallucinations in Parkinsons.

A

slowly discontinue medications that may be contributing
-amantadine, DA agonists, anticholinergics, sedatives
avoid 1st gen APs, olanzapine, risperidone, aripiprazole
clozapine: efficacy but not used due to agranulocytosis
quetiapine: less evidence but does not worsen PD sx
-start low and go slow

PHAR358 (20 decks)

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