Parkinson's Flashcards
What are the motor complications associated with Parkinson’s?
- decreased ability to perform ADL’s (activities of daily living)
- increased risk for falls and fractures
What are the NON-motor complications associated with Parkinson’s?
- cognitive impairment/dementia
- apathy, depression and/or psychosis affect QoL
- swallowing, GI, speech difficulties
What are thought to be the causes of Parkinson’s?
- head trauma
- genetic
- environmental (exposure to pesticides, well water?)
why is DA deficiency important?
DA deficiency is responsible for the core motor features
- neuronal injury/loss of substantia nigra pars compacta (MAJOR source of DA projections to basal ganglia)
- prion-like pattern spread of misfolded proteins from peripheral tissue to brainstem (early premotor and non-motor sx)
- motor symptoms present
- cortical regions! = late onset dementia
What mechanisms cause PD?
- mitochondrial dysfunction
- oxidative stress
- neuroinflammation
- faulty protein degradation
Bradykinesia definition
slowness of movement
- gait
- facial expressions
- ask them to snap, stand/sit
- tremor
Parkinsonism diagnosis:
Bradykinesia + (tremor OR rigidity)
Parkinson’s diagnosis:
- clinical exam
- MRI (to rule out hydrocephalus, diffuse vascular disease or mass/lesions if UNUSUAL presentations)
- SPECT (single-photon emission computed tomography): nuclear imaging scan that integrates computed tomography and a radioactive tracer
Parkinsonism vs Parkinson’s
ParkinsonISM:
- secondary to neurodegenerative disorders
- Drugs (metoclopramide, FGA & SGA)
PD:
- idiopathic (unknown cause)
What are the symptoms of PD?
- stooped posture
- masked face
- back rigidity
- forward tilt of trunk
- flexed elbows and wrists
- hand tremor
- reduced arm swing
- tremors in the legs
- slightly flexed hip and knees
- shuffling/short stepped gait
What features support diagnosis of Parkinson’s?
- unilateral onset of tremor, bradykinesia, rigidity
- persistent asymmetry of motor signs
- falls (later in progression)
- significant loss of smell
What features exclude diagnosis?
- essential tremor (postural & kinetic vs resting)
- symmetry of motor signs at onset
- falls at presentation or EARLY
- strokes with stepwise progression of parkinsonian feature
- head injuries
- encephalitis
- neuroleptic tx at onset of sx
- sustained remission
- early/severe autonomic involvement, disturbances of memory, language, and praxis
- cerebral tumor
- supernuclear gaze palsy
- negative response to lots of levodopa
- MPTP exposure
How do PD patients typically respond to levodopa?
excellent response
> 10 yr response
(severe levodopa induced chorea)
What are the motor related S&S?
T remor
R igidity
A kinesia/bradykinesia
P ostural instability
What are the NON-motor related S&S?
- malaise
- easily fatigued
- subtle personality changes
- sleep disorder
- constipation
- pn
- depression
- dementia
What does a tremor of PD look like?
slow frequency; AT REST
- inhibited during movement & sleep
- aggravated by emotional stress
- pill rolling quality
- look at upper & lower extremeties @ rest
- have pt reach out hands, tremor would reemerge after several seconds delay
Rigidity defintion:
resistance to efforts by the clinician to elicit passive joint movement
- may be any part of the body & related to stiffness/pn
- examine for rigidity & ask about stiffness/pn
Bradykinesia definition:
generalized slowness of movements & repetitive movement fatigue
- may be decr. facial expression, difficulty with fine motor tasks, speaking softer, difficulty turning/getting out of bed/chair/car, shortened or dragging steps
- observe sitting/walking
- pt complains of: weakness, sluggishness, tiredness
Surgical intervention?
- ablative surgery
- pallidotomy (posterolateral part of the globus pallidus interna – contralateral dopamine)
- thalamotomy (ventral intermediate nucleus – contralateral intractable tremor)
- deep brain stimulation
- –> thalamic stimulation (ventral intermediate nucleus)
- –> pallidal stimulation
- –> subthalamic stimulation (best at decr. contralateral bradykinesia & tremor)
Non-pharm options
- PT
- OT
- Speech
- Psychology
generally VERY beneficial
- exercise may help improve motor function
What meds do we use in early disease?
MAO-B (selegiline, rasagiline, safinamide)
Amantadine
Anticholinergics (cogentin, artane)
DA agonists (requip, mirapex, neupro)
When do we avoid anticholinergics?
patients > 70 yo
When do we want to use DA agonists?
< 65 yo
Selegiline
early stages of PD or adjunct to L-dopa (delay levo by 9 mo)
- improves wearing off
- DI: meperidine, DM, sympathomimetic amines, SSRI
(MAO-Bi)
What are MAO-Bi known for?
worsening dyskinesias
Rasagaline
- mono or adjunct to levo
- improves wearing off
- treat motor complication of random-off
CI: cyclobenzaprine, mirtazapine, St. John’s wort, meperidine, methadone, tramadol, DM, sympathomimetic amines
Safinamide
adjunct tx of wearing off (without worsening dyskinesias)
- no dietary restriction of tyramine
CI: MAOi, opioids, DM, SNRI, TCA, Cyclobenzaprine, methylphenidate, amphetamines, St. Johns wort
Amantadine
EARLY PD
* benefit w/i a couple of days
improve dyskinesias & may alleviate tremor!
CAUTION: geriatric
SE: livedo reticularis (reddish mottling of skin), ankle edema, hallucinations
(+) decr. severity of dopa induced dyskinesias (antiglutamatergic)
(-) tolerance may develop, cognitive SE, withdrawal potential
Anticholinergics
(benztropine, trihexyphenidyl)
- tremor = not relieved by agonist or l-dopa
- combo c other meds for PD
- improve bladder dysfunction (female) & drooling
- not in pt > 70 yo
Anticholinergic AE
- forgetfulness/ decr. ST memory
- hallucinations, psychosis
- dry mouth
- blurred vision
- constipation
- trouble with urination (worsens BPH)
What do we use in mod-severe disease?
- DA agonists
- Levodopa/carbidopa
- Combo tx
Peripheral AE of DA agonists
- N/V
- ortho HoTN
Central AE of DA agonists
- motor changes
- dyskinesias
- psychiatric disturbances
- pedal edema
- pleuropulmonary (ergots)
Are DA agonists or L-dopa more likely to cause dyskinesias?
L-dopa
DA agonists
(+) antiparkinsonian effects, decr. risk for l-dopa related motor complications
(-) neuropsych SE, erythromelagia, pedal edema, sedative SE
- 4-6 wks before you can see improvements
L-dopa counseling points
- avoid giving WM to improve absorption in severe disease
AE:
- dopaminergic
- peripheral (usually controlled by adding carbidopa)
- central
- at least 3 days bw dose adjustments
- 2-3 wks for therapeutic response (quicker than DA agonists)
L-dopa advantages & disadvantages
(+) best anti-parkinsonian drug, works with most pts, maybe improve mortality?
(-) SE, dyskinesias/dystonias, motor changes, neuropsych sx, sedation
Initial tx: levodopa/carbidopa
- age
- funct
- AE
- all pt
- sustained tx benefits
- dyskinesias/ motor fluctuations
Initial tx: DA agonists
- age
- funct
- AE
- immediate tx response NOT needed (< 65 yo)
- decr. risk of dyskineasias/motor complications
- incr. risk for impulse control disorder
What agents are adjunct tx?
- COMTi
- apomorphine
- istradflylline (adenosine a2 blocker)
Catachol-O-methyl-transferase (COMT)
- extend levodopa effect = decrease “off” time
- may incr. dyskinesias –> DECR. L-dopa dose
COMTi AE
- diarrhea
- central & peripheral DA SE
- liver toxicity (tolcapone)
COMT (+) & (-)
(+) decr. “off” time, enhanced motor responses in pts with L-dopa motor fluctuation, improved ADL scores if stable L-dopa responders
* better if at onset of L-dopa tx
(-) DA SE (dyskinesias), discoloration of urine,
- tolcapone: explosive diarrhea, liver tox
Apomorphine
- acute, intermittent tx of hypomobility “off” episodes
CI: 5HT3 & COMTi
AE:
- severe N/V (coadmin w/ trimethobenzamide)
- angina
- cardiac arrest
- HoTN & ortho HoTN
- MI
- syncope
Istradeflylline
- for “off” periods as adjunct to carbi/levo
special dosing for:
- smoking > 20 cig/d = 40 mg
- on CYP3A4i = 20 mg
- CYP3A4 inD = DO NOT USE
Istradeflylline AE:
- dyskinesias
- dizziness
- constipation
- N
- hallucinations
- insomnia
What happens with DA excess?
- dyskinesias
- hallucinations
- delusions
What happens with DA deficiency?
worsening PD symptoms
What do we do abt: Random off?
sx unrelated to med dosing time
- entacapone and rasagiline
- pergolide, pramipexole, ropinirole, tolcapone
- apomorphine, cabergoline, selegiline
What do we do abt: wearing off?
sx @ the end of dosing interval (plasma levels decr.)
- incr. dose frequency
- CR carb/levo
- DA agonist
- selegiline, rasagiline
- COMTi
- amantadine
What do we do abt: dyskinesias?
involuntary movements during PEAK plasma levels
- amantadine
- smaller/ more frequent doses
What do we do abt: dystonias?
sustained muscle contractions/ abnorm postures (distal lower extremeties)
- HS SR carbido/levod
- DA agonists
- baclofen
- botulinum toxin
What can we use for depression in PD pts?
- SSRI, SNRI, bupropion
- TCADs (amitriptyline, nortriptyline, desimpramine)
- caution c worse cognition, ortho HoTN –> fall risk
(pramipexole with motor & mood sx are targeted
What can we use for psychosis with PD?
- Quetiapine
- Pimavanserin
- Clozapine
What about PD + mild cognitive impairment?
- atomoxetine
What about dementia + PD?
- donepezil
- rivastigmine
What if pt experiences ortho HoTN?
- incr. fluids + Na consumption, elevate head of bed, compression stockings (non-pharm)
- fludrocortisone
- midodrine
What is Sialorrhea?
How do we treat?
excess drooling
- glycopyrrolate/scopolamine transderm
- botulinum tox
- atropine drops
