Parkinson/Dementia TBL Flashcards
(PH-1) Describe rationale for and the mechanism of action of L-dopa and L-dopa plus carbidopa in the treatment of Parkinson disease, list their side effects, and describe the motor fluctuations observed in patients receiving these medications (PH-2) List the prototype indirectly-acting dopamine agonists used in the treatment of Parkinson disease, describe their mechanism of action, and list their major side effects (PH-3) List the prototype MAO and COMT inhibitors used in the treatment of Park
MOA of Levadopa
converted to dopamine by DOPA decarboxylase
Why can’t dopamine just be given?
dopamine has low bioavailability and cannot cross BBB
enzyme that converts Levadopa to dopamine
DOPA decarboxylase
reason for giving carbidopa with levadopa
inhibits DOPA decarboxylase in the periphery, reducing side effects, increasing plasma half-life of levadopa
main effect of levadopa
reduces bradykinesia
dope dependant effects of Levadopa
GI problems, postural hypotension and rarely heart problems
main frequent side effects of Levadopa
dyskinesias (chorea, ballismus, myclonus, tics, tremor) anxiety, agitation, delusions, depression
conditions for which levadopa is contraindicated
hx of psychosis
bromocriptine class
partial D2 agonist
pramipexole class
partial D2 agonist
ropoinirole class
partial D2 agonist
most common movement SE in levadopa
choreoathosis of face and distal extremities
apomorphone
partial D2 agonist
bromocriptine use
pts refractory or cannot tolerate lavedopa
SE of bromocriptine
postural hypotension, arrythmias, dyskinesias, mental status changes
first line drugs in early onset PD
pramipexole, ropinirole
SE of pramipexole, ropinirole
Anorexia, n/v, dyskinesias, sleepiness and fatiuge
drug that should be reduced in renal dysfunction
pramipexole
drug taht may interact with caffiene and warfarin
ropinirole
drug with D3 affinity
pramipexole
subQ injectable PD drug
apomorphine
temporary relief of “off periods:
apomorphine
PD drug causing severe nausea
apomorphine
PD drug that only is effective for a few weeks
amantadine
PD drug causing lace like face rash
amantadine
PD drug that can cause acute toxic psychosis
amantadine
seleglinine MOA
increases dopamine, by inhibiting MAO B - which metabolizes dopamine to NE and serotonin
metabolizes dopamine to NE and Serotonin
MAO B
used as adjunct to levaopa or alone in new pts
seleglinine
SE of seleglinine
insomnia, GI issue,
PD drug that can cause serotinin syndrome
selegiline
bad serious drug interaction with selegiline
meperidine
COMT inhibitors
entacapone and tolcapone
adjunct to levadopa to improve “on-time”
COMT inhibitors
SE of COMT inhibitors
dyskinesia, GI distress and postural hypotension, orange urine
increases liver enzymes and can cause actute liver failure
tolcapone
MOA of antimuscarinic drugs in PD
decrease exititory cholinergic neurons in striatum by blocking muscarinic receptors
antimuscarinic PD drugs
benzotropine, trihexyphenidyl
SE of antimuscarinic PD drugs
drowsiness, inattention, confusion, hallucinations, atropine like effetcs
PD drugs that increase tardive dyskinesias form AP drugs
antimuscarinic PD drugs
Alzeheimer cholinesterase inhibitor drugs (3)
donepezil, rivastigmine, galantamine
SE of Alzeheimer cholinesterase inhibitor drugs
n/v, diarrhea, vomiting, anorexia, weight loss
reason for Alzeheimer cholinesterase inhibitor drugs
to address defict of ACh in brain
MOA of menantine
blocks NMDA receptor that binds glu
use of menantine
moderate to severe Alzheimer’s
drug class to use in treating depression in alzheimer’s
SSRI
cardinal features of PD
tremor at rest , bradykinesia, rigidity
late feature of PD
postureal instability
motions to clicially observe bradykinesia
finger tapping, hand gripping, pronation/supination hand movements, heel ot toe tapping
main way to distinguish movement sx in PD from others
PD usually begins one sided and remains stronger on that side as it procedes bilateraly
test for rigidity
pasivly manipulating the limbs
test of postural rigidity
“pull test”
PD sx least responsive to dopaminergic therapies
postural instability
nonmotor sx of PD
dementia, psychosis, hallucinatiions, mood disorders, sleep problems, autonomic dysfunction, pain and sensory disturbances
nonmotor sx of PD that can predict mortality
congnitive dysfunction and mortality
PD sx that can predict onset of dementia
older age, severity of motor sx, hallucinations, depression, FMX of dementia
type of dementia in PD
subcortical
sx of subcortical dementia
psychomotor retardation, memory difficulty, alterned personality
dementia normally found in alzheimer’s but not PD
aphasia/apraxia
main neuropathologic finding in PD
lewy bodies, as well as amyloid plaques.neurofibrillary tangles
ddx of PD when motor and dementia sx occur at onset
lewy body dementia
imaging study that should be done in suspected PD
MRI to rule out structural abnormalities
dx criteria of PD
bradykinesia and either tremor and/or rigidity. response to dopaminergic therapy, rest tremor and asymetric sx
non drug thereapy for PD
exercise, speech therapy, nutrition counseling
histoligic findings in Alzheiners
Beta - amyloid plaques and neurofibrillary tangles
protein found in CSF of alzheimer’s pts
tau
genetic polymorphism in alzeheimer’s
APOE on chromosome19
diognostic criteria of Alzheimer’s
1) short-term memory impairment,
2) one or more of:
- aphasia
- apraxia
- agnosia
- disturbance in executive functionin
3) gradual onset and continuing cognitive decline
4) not due to another underlining disease
age determining early.late onset alzheimer’s
65
sx of Lewy body dementia
parkinsonion sx, dementia, visual hallucinations, rapid course
histologic finding in Lewy body dementia
eosinophilic inclusion bodies in cerebral cortex and brainstem
drugs NOT to give in Lewy Body dementia
conventional Anti-psychotics
histopathology of frontotemporal dementia
tau-positive inclusions
sx of frontotemporal dementia
disinhibtion and shallow effect OR early and progressive loss of expressive launguage and severe naming difficulties
sx of huntingtons
psych - depression, anxiety, irritability, hallucinations, delusions. Physical sx of chorea
sx of CJD
rapidly progressing dementia with severe cerebellar/extrapyramidal signs and myoclonus
type of CJD with longer course
vCJD
medical conditions that can mimic dementia
diseases of basal ganglia, cerebellum degeneration, encephalitis, MS, Wilson’s disease, neuronal storage disease
treatable causes of demantia
vascular disorders, normal pressure hydrocephalus, infections, metabolic disorders, nutritional disorders
imaging findings in dementia
cortical atrophy and enlarged ventricles
score on MMSE suggestive of imparment
25/30
score on MMSE definitive for impairment
20/30
early behavioral stages of dementia sx
sugtle change in personality, decrease in interests, apathy and labile emotions, slight loss of high performance function
middle behavioral stages of dementia sx
early changes more pronounced, possible psychosis, poor insight
advanced sx of dementia
imability to perform tasks of daily living, incontenince, extreme emotional lability, inability to recognize friends and relatives
end stage of dementia sx
mute and unresponsive, death within a year
noncog sx of dementia
hallucinations and dementia, depression,
ddx to lead to depression rather than dementia
recent weight loss, worsening sleep, crying, self-deprecating comments, social withdrawal, psychomotor agitation and negativism
imagint that can be used to identify type of dementia
PET
PET findings in alzheimer’s
temporal and parietal hypometabolism
drug used for younger PD pts
Ropinerole, pramipexole
addition to L-dopa when it starts not to work as well
entacapone
how many substantia nigra neurons need to be lost to have PD sx
80%
Ropinirole acts mainly on
the post-synaptic neurons in the indirect nigrostriatal pathway
PD drug acting mainly in the periphery
entacapone
