Parkinson Dse Flashcards
Peak age of onset of PD
6th decade
Tetradof PD
Hypokinesia, Bradykinesia
Resting tremor
Postural instabilility
Rigidity
CF of PD
Expressionless face (hypomimia), stooped posture, festinating gait
Speech in PD
Monotomous soft cluttered
early sign of PD
Infrequency of blinking
initial sign of PD
Tremor - 4 per sec pill rolling tremor of thumb and fingers
Aborts tremor in PD
Complete relaxation
Rigidity
Cogwheel rigidity
Graphia in PD
Micrographia
Speech do in PD
Hypokinetic dysarthria
Gait in PD
Festinating gait - rapid but short steps
Walking in PD
Reduced to shuffle
Spine in PD
Extreme forward flexion
Tremors in PD
begin in 1 limb spread to one side -> both limb
Inability to resist blinking in response to taapping bridge of nose or glabella
Myerson sign
DDx of Parkisonism
PD Progressive supranucleur palsy Dysautonomia Lewy body dse NPH
indicates PD
Sustained response to Levodopa
Rapid onset of Parkinsonism
Neuroleptic meds, Metoclopramide
Pathology of PD cells and nuclei
Loss of pigmented cells in substantia nigra and other pigmented nuclei
Pathology of PD, what appears pale
Substantia nigra appears pale
Histopath of PD
Eosinophilic cytoplasmic inclusions surr by faint halo (Lewy bodies)
Other regions ofn euronal loss in PD
Mesencephalic reticular formation, sympathetic ganglia
Causes destruction of dopaminergic neurons
MPP+
MPTP converted to what which produces irreversible Parkinsonism
MPP+
This mutatation is the mc genetic abn in EARLY ONSET PD
Park2 (parkin)
early onsent PD
parkin, alpha synuclein
normal component of synapse but in high concentration, aggregates and is a main constituent of Lewy Body
Alpha synuclein
Other constituents of LB
Ubiquitin and tau
Ubiquitin protein ligase that functions in removal of unnecessary proteins from cells
Parkin
Mutation of parkin leads to
Misfolding of synuclein
In PD, what cells are lost? What NT is loss?
Substantia nigra cells loss
Dopamine input loss
With lost of DOPAMINE in PD, 2 nuclei become overactive
Subthalamic nucleus
Globus pallidus interna
2 anatomic targets in Deep brain stimulation
Subthalamic nucleus
Globus pallidus interna
Tx of PD most effective
L Dopa and L Dopa modifying drugs
Crosses BBB
L Dopa
Does not cross BBB
Dopamine
Motor complications
Fluctuations (“on-off)
Dyskinesias
Wearing off effect
Delayed on
Decarboxylase inhibitor
Carbidopa
Moa of Carbidopa
inhibits L dopa decarboxylation –> More of L dopa available –> crosses BBB
Dose L Dopa-Carbidopa
Levodopa/Carbidopa 25/100 mg BID titrated to 4 tablets 5 or more times daily
Tx of PD extends plasma half life of L dopa
COMT Catechol.o.methyltransferase inhibitors
COMT Catechol.o.methyltransferase inhibitors MOT
extends plasma half life of L Dopa
COMT Catechol.o.methyltransferase inhibitors sample
Entacapone
Directly act on dopamine rc
Dopamine agonists
Dopamine agonists MOA
Directly acts on dopamine rc
May be initial tx esp younger individuals
Dopamine agonists
Less likely to cause DYSKINESIAS
Dopamine agonists
Donwside of dopamine agonists and AE
Less potent
More motor and cognitive SE
Dopamine agonists are derivatives of
Ergot
Dopamine agonists Ergot derivatives
Bromocriptine
Pergolide
Cabergoline
2nd gen dopamine agonists
Ropinirole, pramipexole (minimal ergot)
Rotigotine patch
2nd dopamine agonists Minimal ergot like effects
Ropinirole and premipexole
2nd dopamine agonists patch
Rotigotine
Adjunctive meds in PD
Trihexyphenidyl and benztropine (anticholinergic) for tremors
Amantidine - antiviral
adjunctive meds (anticholinergic) for tremors
Trihexyphenidyl and benztropine
Adjunctive meds antiviral
Amantidine
Moa of Amantidine (adjunctive meds)
NMDA antagonist
Antiviral
Mild tremors on tremor hypokinesia postural sx
Amantidine
Neuroprotective agents
MAO B inhibitor reduces oxidative stress (Selegeline, Rasagiline)
Ropinirole, pramipexole
Vitamin antioxidants (Vit E)
Mao B inhibitor samples
Selegeline and Rasagiline
MAO B inhibitor (Selegeline, Rasagiline) moa
reduces oxidative stress
SE of dopamine tx
nausea dyskinetic movements end of dose reduction on-off phenomenon (motor fluctuations) psychosis depression, patho gambling
Reduction of tremor and bradykinesia
L DOPA Carbidopa-L-dopa
May prolong L dopa effects
Controlled release Carbidopa-L-dopa
Moderate effects on all aspects; reduced motor fluctuations of L dopa, less dyskinesia
Dopamine agonists (Ropinerole, Pramipexole)
Smoothing of motor fluctuations
Glutamate antagonist (Amantidine)
Tremor reduction
Anticholinergics (Benztropine, Trihexyphenidyl)
Prolonged effect on L Dopa
COMT inhibitors (Entacapone)
Reduced off time, Neuroprotection
MAO inhibitors (Rasagiline, Selegline)
SE meds
Nausea
DYSKINESIA
Orthostatic hypotension
L Dopa Carbidopa-L-dopa, Controlled release Carbidopa-L-dopa
SE meds Orthostatic hypotension Excessive sleepiness CONFUSION hallucination
Dopamine agonists (Ropinirole, Pramipexole)
SE meds Leg swelling CHF Prostatic outlet obstruction Insomia
Glutamate antagonists (Amantidine)
SE Meds Dry mouth Urinary outlet obstruction Confusion Psychosis
Anticholinergics (Benztropine, Trihexyphenidyl)
SE Meds
Urine discoloration
diarrhea
dyskinesias
COMT inhibitor (Entacapone)
SE of meds
Hypertensive crisis with tyramine rich foods and sympathomimetics
MAO inhibitors (Rasagiline, Selegiline)