Movement Disorders - Rothrock Flashcards
Which pyramidal tract is involved in motor?
corticospinal tract
What are the extrapyramidal motor tracts.
Basal ganglia cerebellar vestibulospinal rubrospinal "Mollaret's Triangle"
Parkinsonism is when ACh levels are far greater than (blank) levels
dopamine
Choreoathetosis is when Dopamine levels are far greater than (blank) levels
ACh
PD is a loss of dopaminergic neurons in the (blank) tract
nigrostriatal
PD leads to a shortage of DA in which circuit?
extrapyramidal motor cicrcuit
t/F: parkinsonism is the same thing as PD
false
What part of the substantia nigra is the primary victim of PD?
pars compacta
Where do the fibers of the pars compacta project?
to the corpus striatum which is made up of the caudate and putamen
what is the avg. age of onset of PD?
55 years
how does PD affect the sexes?
male:female 3:2
what percent of the nigrastriatal neurons are lost before the motor signs of parkinson’s emerge?
60-80%
what are the potential causes of PD?
- idiopathic
- genetic
- environ. toxins
- diet
- multiple causes
- alpha synuclein lewy bodies
what type of ACh receptors are overactivated in PD?
mACh which leads to increased GABA release
What is the acronym for the clincal signs of parkinsonism?
Tremor
Rigidity
Akinesia (or bradykinesia)
Postural changes (loss of righting reflex, stooped posture)
What is PD characterized by posturally?
stooped posture, EXAGGERATED FLEXION
What are the ancillary features of PD?
sialorrhea (drooling) micrographia hypophonic speech with decreased inflection slow thinking subcortical dementia
Is PD characterized by symmetrical or asymmetrical movement?
asymmetrical
what are the drugs that increase DA levels?
- levodopa
- MAO-B inhibitors (rasagiline/Azilect)
- COMT inhibitors (entacapone/Comtan aka carbidopa)
- DM receptor agonists (Requip)
What is the other treatment option for PD that is not increasing DA levels?
anti-ACh
anitmuscarinics (Artane)
what is the most robust therapeutic for PD?
levodopa
How does levodopa enter the brain?
via the L-amino transporter
Can actual dopamine cross the BBB?
noooope
what is the issue with levodopa half life?
short; end-of-dose effect is common; peak-dose effect leads to hyperkinesia
What enzyme converts levodopa to Da?
L-amino acid decarboxylase (DOPA decarboxylase)
Where in the body is DOPA decarboxylase found?
peripheral tissue and in the brain!
Because of the presence of DOPA decarb’ase in the periphery, what do we give with L-DOPA and why?
carbidopa, a DOPA decarb’ase inhibitor that DOES NOT CROSS THE BBB to increase effective dose of L-DOPA reaching the brain
what are the SE of levodopa?
N/V
orthostatic hypotension
hallucinations and distorted thinking
dyskinesias, fixed dystonias, choreoathetosis
Amantadine promotes DA release from the…
substantia nigra
In what severity of PD do you use amantadine?
early/mild cases of PD
which DA increasing drug shows tachyphylaxis?
Amantadine; effects are short lived
What are the SE of amantadine?
restlessness, insomnia, agitation
hallucinations and confusion
livedo reticularis (lacy purple skin discoloration)
How do MAO-B inhibitors work?
inhibit DA metabolism; good for early/mild PD; use with levodopa/carbidopa for adv. PD
What are the SE of MAO-B inhibitors?
confusion, hallucinations
Enhance DA SE (GI distress, dyskinesia) when taken with levodopa
Serotonin syndrome in pts taking SSRIs
T/F: COMT is only found in the brain
false; found in brain and peripheral tissues
What is the action of COMT?
converts levodopa to 3-O-methyldopa which competes with levodopa for transport into the brain
T/F: COMT inhibitors can be used as monotherapy
false; used as adjunctive with levodopa
Where do the COMT inhibitors work?
in the periphery so the levodopa can make it to the brain
What are the SE of COMT inhibitors?
N/V
Urine discoloration (orange, red, brown, or black)
sleep disturbance
DA receptor agonists activate which DA receptor?
D2 receptors
What is the plus of using a DA receptor agonist over levodopa?
provider a smoother and more continuous receptor activation and rarely cause dyskinesia
T/f: D2 agonists require functional DA neurons
false; that’s why they are good in adv. PD where there are few DA neurons!!
T/F: D2 agonists can be used as monotherapy
true; in early cases of PD
what’s the plus for using D2 agonists with levodopa?
decrease the “off” period and decreases the dose requirement
What are the side effects of D2 receptor agonists?
Dizziness and hallucinations Impulse control disorders Hypotension Insomnia Nausea
What completely unrelated dz are D2 agonists also indicated for?
restless leg lol
which D2 agonist is a ergot alkaloid?
Parlodel
Which D2 receptor agonist is used to treat neuroleptic malignant syndrome?
Parlodel
What are the clinical signs of NMS?
rigidity, tremulousness, fever, autonomic instability (BP), agitation>delirium>coma
plasma (blank) is elevated due to rhabdomyolysis from NMS
plasma CPK
T/F: NMS progresses rapidly and requires aggressive tx
true
What causes NMS?
typical antipsychotics like butyrophenones, phenothiazines, and promethazine
ALSO atypical antipsychotics
mACh receptor agonists may improve tremor in early PD but have little effect on (blank and blank)
rigidity and bradykinesia
What are the side effects of mACh receptor agonists?
dry mouth
urinary retention
confusion and memory impairment
(think opposite of SLUDGE syndrome)
what is the treatment strategy for PD in pts younger than 65?
- more emphasis on long-term considerations
- start with D2 agonist
- add levodopa/carbidopa when agonist no longer sufficient
What is the treatment strategy for older pts with PD?
- emphasis on providing symptomatic relief w/ few SE
2. use levodopa/carbidopa
T/F: pts that only have mild tremor can go on anti-mACh monotherapy
true
deep brain stimulation targets which two brain structures?
subthalamic nucleus and globus pallidus internus
what is the target Sx for deep brain stim?
tremor; DBS less likely to help balance and gait
excessive off time
DA-responsiveness
Sig. dyskinesia with current meds
t/F: initial trial of levodopa/carbidopa can be used to help confirm a PD Dx
true
What drugs are the preferable initial rx?
D2 agonist and MAO-B inhibitors; especially in younger pts
T/f: COMT inhibitors can be used in monotherapy
false; use w/ levodopa
What are the signs of Progressive supranuclear palsy?
impaired eye movements (vertical) -- doll's eye axial rigidity mild, slowly progressing dementia dysphagia refractory to PD meds
Describe a physiologic tremor
Action tremor:
symmetric, high freq/low ampl; may involve speech; worse w/ fatigue, caffeine, exposure to cold; better w/ alcohol
Describe an essential tremor
may involve the head; autosomal dom inheritance
describe the parkinsonian resting tremor?
asymmetric, low freq/high amplitude; tends to spare speech and head
