L2: Drug Treatment of Motor Disorders Flashcards
what mediators do microglia release when activated?
NO-, COX-2, O2-
give examples of what activates microglia
Beta-amyloid plaques, stroke, TBI, infection, pollutants, genetic factors
what is associated with parkinson’s disease (symptoms)
increasing disability of movement
mean age of onset of PD
55 years
what % of PD is genetic/familial
10%
what is the autosomal dominant genotype of PD
Mutation in the alpha-synuclein protein that plays a role in synaptic vesicle trafficking and neurotransmitter release
monkey’s exposed to what produces symptoms like PD?
MPTP - an opioid analgesic
describe the pathway involved in PD (Normal vs PD)
normal: DA neurons in the substantia nigra normal inhibit GABAergic output in the striatum and cholinergic neurons exert an excitatory effect.
In PD: loss of DA neurons, no impact on cholinergic neurons, hyperactivity of cholinergic neurons causes excitotoxicity which contributes to the symptomology of PD
describe the autosomal recessive PD
Mutations in parkin, PINK1, DJ01 gene
describe atropine
atropine is a muscarinic receptor antagonist which aims to antagonise cholinergic receptors to account for the loss of DA neurons.
side effects of atropine
dry mouth, constipation, urinary retention
describe L-dopa
precursor of DA that can cross BBB, does not stop progressive loss of DA neurons in SN, rec. for older patients as it only works for around 10 years
what drugs can atropine be given with to improve PD-like symptoms?
antipsychotics
what drugs should be used in earlier onset PD
not L-dopa, DA-R antagonists, anticholinergics, deep brain stimulation, monoamine oxidase inhibitors, amantadine
describe the gene mutation associated with Huntingtin’s Disease
CAG repeats (35+) causing an N terminal polyQ (glutamate) tail on the Huntingtin protein
what loss of neurons is associated with HDD
Selective loss of neurons projecting from the efferent branch of the striatum of the basal ganglia, death of neurons also seen in globus pallidus and cerebral cortex
what is disease severity of HD directly linked to?
the length of the PolyQ tail at the N terminal of the Htt protein