parkinsons

parkinsons risk factors

parkinsons risk factors

advanced age, genetics, environmental exposures

parkinsons protective factors

caffeine, cigarette smoking, aerobic exercise (?)

pathophys of parkinsons

a complex interplay of several cellular processes lead to neuronal damage

• toxic biochemical rxns leading to oxidative stress

• abnormal cell signalling pathways that result in spontaneous cell death (i.e apoptosis)

• dysfxnal protein degradation systems resulting in cytoplasmic protein accumulation and misfolded proteins

List the clinical presentation sx of parkinsons

Tremor

Rigidity

Akinesia/Bradykinesia

Postural Instability

How is a true parkinsons diagnosis established

must have akinesia/bradykinesia + one of the other three symptoms

Explain the tremor present in parkinsons

occurs at rest and is a pill rolling tremor

often intermittent in early stages

occurs most often in upper extremities, but may be evident in legs, lips, jaw, tongue (rarely involves the head)

explain rigidity in parkinsons

Resistance to passive movement

increased muscle tone

pts often complain of stiffness and pain

can have lead piped rigidity or cogwheel rigidity

reduced arm swing and stooped posture are often indicative of rigidity

lead pipe rigidity

a consistent state of rigitidy throughout full ROM

cogwheel rigidity

ratchet like stop and start movement pattern

occurs if concomitant tremor

explain akinesia/bradykinesia sx of parkinsons

generalized slowing of movement w/ loss of amplitude

very debilitating and occurs in all pts

typically occurs first in digits of upper extremeties: difficulty w/ ADLs, micrographia

in lower extremities- presents as shuffling gait or dragging of the feet/legs

explain postural instability sx of parkinsons

centrally-mediated postural reflexes become dampened

pts experience a feeling of imbalance, increasing fall risk

occurs later in disease process

pattern in which sx occur initially in parkinsons

asymmetrical, unilateral

examples of meds which can cause parkinsonism

antipsychotics

metoclopramide

lithium

SSRIs

CCBs

valproic acid

how to do a differential diagnosis for med-induced parkinsonism

is there a temporal relationship

• occurs within 3mo of med start/dose increase but may be delayed up to a year (therefore hard to tell if temporal)

are the symptoms symmetrical

• meds will cause bilateral sx but parkinsons causes unilateral initially

does the sx respond to med d/c

• d/c med

• Sx may take 7 days-several mo to resolve therefore difficult to tell

do they have dopaminergic neuron loss sx

• loss of sense of smell (bc of DA neuron loss) is prob not med induced, prob real parkinsons

PD treatment is targeted at doing what

Sx control

non pharm

patient education (parkinson.ca)

regular exercise: aerobic, strength, balance and gait training

speech, occupational and physical therapy

surgical options: lesioning procedures, deep brain stimulation

3 main things to consider when deciding on parkinsons Tx

severity/impact on QoL

type of Sx

age

If someone has no/minimal sx or fxnal impairment what are treatment options?

watch and wait

MAO-B inhibitor

amantadine

anticholinergics

what type of patient is anticholinergics rx for

younger, tremor predominent (no significant bradykinesia)

Ex of MAO-B inhibitors

Selegiline, Rasagiline, Safinamide

Problem with Selegiline

structurally similar to amphetamines therefore can cause insomnia

how to avoid/fix insomnia with selegiline

second dose given @ noon or v early afternoon

Which MAO-B inhibitor causes the most confusion

selegiline

Which MAO-B inhibitor is most commonly used + why

Rasagiline due to once daily dosing and it is well tolerated

Which MAO-B inhibitor is most potent

rasagiline

When is Safinamide used

add on therapy for treatment of wearing off (not commonly used)

AE of MAO-B inhibitors

vivid treams, dizziness, insomnia, constipation

Drug interactions with MAO-B inhibitors and their management

SSRIs/serotonergic agents

• MAOB inhibitor is v selective to MAOB which primarily affects DA.

• May see combined with SSRI as depression is v common comorbidity

• Monitor for serotonin syndrome, do risk v benefit assessment, check for other serotonin meds on file

Tyramine containing foods

• can have up to 75mg tyramine

• should give them chart on tyramine foods

ex of anticholinergics used for parkinsons

benztropine

trihexyphenidyl

most common anticholinergic used

benztropine

Who should anticholinergics not be used in

not the DOC for 65+ And dementia (bc of AE’s)

should not be used in pts with dyskinesias or other motor fluctuations

AE anticholinergics

constipation, dry mouth, urinary retention, blurred vision, confusion/cognitive impairment

who is more susceptible to anticholinergic induced cognitive impairment

elders, esp those w/ dementia

how to d/c all agents used in PD

slowly taper

drug options for Mild parkinsons Sx/fxnal impairment

Levodopa-carbidopa

dopamine-agonist

Tx options for those <50 + mild parkinons Sx

levodopa-carbidopa OR dopamine agonist

Tx options for those 50+ and mild parkinsons Sx

levodopa-carbidopa

minimal target dose of levodopa-carbidopa

100/25mg TID or higher

safety/efficacy comparison of LD and dopamine agonists

LD has more motor ae but more effective sx control

dopamine agonists are more likely to cause non motor AEs (including GI aes)

why should you not abruptly D/C dopaminergic agents

NMS like sx

Big difference between LD and controlled release LD

controlled release has bioavailability 70% of IR agent therefore may need 30% dose increase

only have to dose BID therefore may be used earlier in Dx

LD central ae

hallucinations, confusion, drowsiness, dyskinesias

peripheral LD ae

nausea, orthostasis

carbidopa fxn in LD

helps with peripheral AE (nausea, orthostasis) because it blocks peripheral conversion of L-dopa to dopamine which causes dopamine to not be able to cross BBB (we want it to) therefore causes these peripheral ae

target daily dose of carbidopa

70+mg

why do we have a target minimal dose for carbidopa

to prevent peripheral conversion of levodopa

How to administer LD

taking w/ food can help N/V

BUT: avoid taking w/ large meals (delays onset) and avoid protein (competes w/ L-dopa to cross BBB on transporters)

space from iron by 2hr

examples of dopamine agonists

Pramipexole

Ropinirole

Rotigotine

LD vs dopamine agonists: why has less frequent administration

dopamine agonists usually

unique dosage form available w/ dopamine agonists

Rotigotine- transdermal patch

AE dopamine agonists

hallucinations, impulse control disorders, somnolence, edema, weakness

If someone is intolerent to one dopamine agonist what can you do

can try another

if patient is unresponsibe to LD can you try dopamine agonists

no they usually wont respond, if someone has PD it should respond to LD therefore reassess diagnosis

If someone has mod/severe PD sx what agent to try

levodopa-carbidopa

1st motor complication that generally occurs with PD

wearing off phenominom

questions to ask to assess wearing off

do you feel your med works as well for you as it has in the past

about how long after you take LD do your Sx appear

can you describe your Sx for me

how do you take your LD

• evaluate adherence and proper administration

if someone is experiencing wearing off when do Sx usually return

3-4hr post LD dose

sx of wearing off

re emergence of pts typical PD sx: tremor, bradykinesia, rigidity

tremor- more rhythmic in nature and occur around one joint

Vs a dyskinesia- tends to be more disordered, resembling writhing movements

list management options for wearing off of LD

Increase dose and/or frequency of LD

sub or add controlled release LD

add a MAOB inhibitor

add a COMT inhibitor

add a dopamine agonist

Good first strategy for pts experiencing wearing off with LD who are on low dose and not experiencing peak dose dyskinesia

increase dose and/or frequency

what is dose fractionation

lower the individual dose of LD and admin more frequently

When is dose fractionation used

in more advanced PD, where pt is experiencing wearing off but peak dose dyskinesia may be a concomitatant issue

When should you sub or add controlled release LD

patients experiencing wearing off in middle of night/early AM

not recommended for daytime management

cons of controlled released LD

may result in unpredictable responses, including delayed onset dyskinesia

not absorbed aswell as IR tabs making individual dose increases of approx 30% needed in some cases

When/why is it a good idea to add MAOB inhibitor to LD

effective adjunct therapy for treating motor complications

thought to prolong t1/2 of DA and reduce wearing off

which MAOB inhibitors are usually added to LD

rasagiline, safonamide

ex of COMT inhibitor

Entacapone

Why are COMT inhibitors not used as initial management for PD

does nothing on its own and has to be with LD to be effective

AE of COMT inhibitors

may cause peak dose dyskinesia

profuse diarrhea, hallucinations, syncope

brown-orange discoloration of urine, or teeth if tab is bitten

LFTs should be performed q 6mo (sometimes causes liver dysfxn)

effect of COMT inhibitors

may increase “on time” of LD by about 1-2hr per day - may need to reduce LD by 10-30%

How to add a dopamine agonist to LD

initiate @ lowest possible dose + titrate slowly to reduce risk of DA ae’s

LD doses may need to be initially reduced

what population may you want to avoid adding dopamine agonist to LD in

65+ or those with cognitive impairment

Sx of peak dose dyskinesia

Chorieform in nature- large amplitude, twisting/turning, jerky movements

not repetitive or rhythmic

how long after taking dose of LD would peak dose dyskinesia appear

30-90min post dose

options for managing peak dose dyskinesia

add amantadine

reduce dose of LD or other adjunctive Tx

if taking CR LD switch to IR

What should be the first intervention if peak dose dyskinesia occurs

switch CR LD → IR

How to manage peak dose dyskinesia while preventing wear off

dose fractionation (reduce LD dose and admin more freq)

If wearing someone gets peak dose dyskinesia and you try to manage it w/ dose fractionation but they get wearing off anyways what can you do

add dopamine agonist bc it is less likely to cause dyskinesia than LD

If someone is on LD + multiple therapies and is getting peak dose dyskinesia what can you do

reduce or d/c MAOB inhibitor or entacapone

what should be tried before adding amantadine for peak dose dyskinesia

attempt dose reduction of other dopaminergic agents

Why is amantadine not often used when no/minimal sx of PD

bc there is little evidence to support use in early PD and efficacy may decrease in 1-2yrs so its better to save for later

AE amantadine

usually well tolerated

elderly pts may be more susceptible to confusion and hallucinations

peripheral ae

livedo reticularis

ankle/pedal edema

how to Tx GI motility issues in PD

apply general measures for Tx constipation:

• increase fluid and fibre intake

• physical activity

• PEG, psyllium, lactulose

reassess anticholinergic meds

Domperidone (NOT metoclopramide)

Depression options in PD

TCAs- added benefit of anticholinergic properties for tremor

SSRI/SNRI- prefered bc of AE profile but may exacerbate tremor or other motor features (dystonia, akathisia)

meds used for psychosis in PD

Clozapine

• most evidence

• requires strict hematologic monitoring

• bad ae profile

• may reduce tremor

  
  QTP

• used most often

• v well tolerated

which antipsychotics are not used in PD due to ae profile

risperidone and olanzapine

How to distinguish PD from dementia w/ lewy bodies

If Sx of dementia occur more than 1yr after PD sx: diagnose with PD

If Sx of dementia occur <1yr after PD sx: diagnose with lewy body dementia

how to Tx dementia Sx in PD

cholinesterase inhibitors- donepezil and rivastigme

con of cholinesterase inhibitors in PD

may worsen PD sx mainly tremor

Which cholinesterase inhibitor has slightly more efficacy in dementia in PD patients

Rivastigmine

which cholinesterase inhibitor is better tolerated in PD

donepezil

How to manage orthostasis in PD

avoid aggravating factors- large meals, alcohol, warm environments

increase salt intake

tilt head up at night

compression stockings

if no response to nonpharm can use fludrocortisone or midodrine

domperidone for postprandial hypotension