Block 3 Lecture 3 -- Parkinson's Flashcards
What proteins are misfolded in Parkinsons?
alpha-synuclein,
parkin
in the basal ganglia
What are the physiological signs of Parkinsons?
1) alpha-synuclein dysregulation – cortical and nigral Lewy Bodies
2) depigmentation of pars compacta in SN
Describe the prevalence of PD.
2nd most common neurodegenerative disease
- prevalence increases with age
- mean age = 57
- twice as common in males
What are environmental risk factors of PD?
neurotoxins
pesticides during development
TBI
What is the genetic/idiopathic breakdown of PD?
90 percent idiopathic
10 percent genetic
What are the actions of MPP+?
1) free radicle introduction into vesicles after DAT uptake
- - increased cytoplasmic catecholamines – ROS – DA neuron death
2) inhibit Complex I in ETC
- - ROS, death
What PD symptoms start 5-10 years before diagnosis?
1) hyposmia
2) constipation
3) REM-sleep behavior
What are motor sxs of PD?
1) resting tremor
2) cogwheel rigidity
3) bradykinesia
4) postural instability
5) reduced arm swinging, forward tilt, head trembling
6) small handwriting
7) potentially diagnostic
- - hypophonia, dysarthria
What are ANS and sensory sxs of PD?
1) fatigue
2) anosmia
3) hyperalgesia/paresthesia
4) seborrhea
5) sexual dysfunction
6) mixed SNS/PNS effects
- - sialorrhea, diaphoresis, orthostasis
What are CNS sxs of PD?
1) late-onset cognitive impairment in frontal cortex and subcortical regions
- - visuospatial, executive fx
2) depression
3) anxiety
What are goals of PD pharmacotherapy?
1) preserve fx and independence
2) improve mobility
3) improve non-motor sxs
4) delay progression (no drugs for this yet)
What is nonpharm tx for PD?
1) subthalamic nucleus deep brain stimulation
2) surgery
- - pallidotomy, thalamotomy, subthalamotomy
What is the MoA of amantadine?
1) enhances presynaptic DA release
2) DAT blocker
3) anti-cholinergic properties
4) NMDAr antagonist
What is the MoA of benztropine?
M1r antagonist
- b/c DA inhibits ACh release in striatum (ACh = tremor)
- adjunct therapy
What are the ergot-based D2r agonists?
1) bromocriptine
2) cabergoline
3) pergolide
What are the non-ergot-based D2r agonists?
1) pramipexole
2) ropinirole
What are the ADRs of non-ergot D2r agonists?
1) nausea
2) edema
3) orthostasis
4) sedation
5) confusion, vivid dreams, hallucination
6) risky behavior (gambling)
NO CERS (no cares)
What are the direct-acting DAr agonists?
1) non-ergot D2r agonists
2) ergot D2r agonists
What M1r antagonists are used in PD?
1) benztropine
2) trihyexyphenidyl
What are the ADRs of DA replacement?
1) nausea
2) hallucination, dreams
3) insomnia
4) syncope
What are the COMT inhibitors?
entacapone
tolcapone
What are the MAOB inhibitors?
selegiline
rasagiline
What is in stalevo?
L-dopa
carbidopa
entacapone
What’s in Sinemet?
L-dopa + carbidopa
25/100mg TID
