Term
|
Definition
50-70yo
15% have family history
bradykinesia: slowness of movement
muscle rigidity: tremor, posture instability
shiffling gait
frequent falls
cognitive impairment
death due to immobility (pulmonary embolism, aspiration pneumonia) |
|
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Term
|
Definition
ROS or diminished antioxidants or both damage nigrostrital dopaminergic area
dopamine can undergo auto-odidative reactions forming H2O2
Fe and H2O2 cause hydroxyl radicals and cellular damage through proteins, lipids, and DNA
MPTP is metabolized to MPP radical which is a neurotoxin causing the disease |
|
|
Term
| how is dopamine nroken down |
|
Definition
AMO degrades into DOPAC and HDO@
H2O2 is broken into OH by Fe or into water by glutathione |
|
|
Term
| chages in the CNS in parkinsons disease |
|
Definition
loss of pigmented dopamine neuronsin substantia nigra (midbrain)
lewy bodies: abnormal cytoplasmic inclusions
loss of nitrostriatal dopamine neurons (no stimulation to D1/2 increases GABA input to cerebral cortex)
increased ACh: dopamine can no longer inhibit release, increased GABA transmission occurs as result |
|
|
Term
| what are the two dopamine receptors and their function |
|
Definition
D1 stimulates direct pathway
D2 inhibits indirect pathway
dopamine acting on either receptor causes excitatory input for the cerebral cortex |
|
|
Term
| what are the 6 categories of parkinsons therapy |
|
Definition
increased dopamine
direct dopamine receptor agonist
dopamine storage uptake/reelease
inhibit MAO-B
anti-cholinergics
inhibit COMT |
|
|
Term
| what drugs increase dopamine 1 |
|
Definition
|
|
Term
| what drugs are dopamine receptor agonists 4 |
|
Definition
bromoctyptine
perfolide
pramipexole
ropinirole |
|
|
Term
| what drugs are dopaine release/uptake drugs |
|
Definition
|
|
Term
| what drug is a MOA-B inhibitor |
|
Definition
|
|
Term
| what drugs are anti-muscarinic agents 2 |
|
Definition
truhexylphenidyl
benzotropine |
|
|
Term
| what drugs are COMT inhibitors 2 |
|
Definition
|
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Term
|
Definition
| meabolic precursor of dopamine |
|
|
Term
|
Definition
| crosses BBB on active carrier (aromatic AA) so can reach brain but little does |
|
|
Term
| where is levodopa metabolized 3, how |
|
Definition
liver, kidney, GI
formulated with peripheral L-aromatic AA decarboxylase inhibitor (carbidopa) |
|
|
Term
| what are the SE of levodopa no matter how long youve been taking it 3 |
|
Definition
decarboxylation to dopamine in dopaminergic neurons in striatum causes SE
nausea and vomiting (less when combined with carbidopa)
on-off phenomenon |
|
|
Term
| what are the early SE of levodopa 5 |
|
Definition
N/V
orthostatic hypotension
tachycardia
arrhythmia
dark urine |
|
|
Term
| what are the late SE of levodopa 5 |
|
Definition
dyskinesias: choreiform movements
hypersentive receptors
mental disturbance: hallucinations, wild dreams, delusions |
|
|
Term
| what is the on-off phenomenon |
|
Definition
when blood levels of levodopa drop there is an immediate reversal of symptoms (esp in sustained release formula)
deelops 2y into therapy
B6 increases peripherial breakdown and levodopa makes this worse |
|
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Term
|
Definition
| DOC and most effective for parkinsons disease |
|
|
Term
|
Definition
D2 agonist
D1 partial antagonise
may save other dopaminergic neurons from oxidative stress |
|
|
Term
|
Definition
| often used as adjunct to levodopa to lessen on-off phenomenon |
|
|
Term
|
Definition
dyslinesias
orthostatic hypotension
mental disturbance: hallucinations, wild, dreams, delusions
pleuropulmonary and retroperitoneal fibrosis (ergot like) |
|
|
Term
|
Definition
no longer on market
causes heart valve fibrosis due to activation of 5HT 2B receptors
agonist of D1 and D2 receptors
more potent than bromocryptine |
|
|
Term
| MOA pramipexole and ropinirole |
|
Definition
| non-ergot dopamine agonist at D2/3 receptors |
|
|
Term
| USE pramipexole and ropinirole 3 |
|
Definition
first line or adjunct for parkinsons
in pt who have not had levodopa
may delay need for levodopa
restless leg syndrome
fibromyalgia |
|
|
Term
| SE pramipexole and ropinirole |
|
Definition
less hallucinations and orthostatic hypotension (like ergot agonists)
reward seeking behavior: drinking, smoking, gambling |
|
|
Term
| how is pramipexole elimiated by |
|
Definition
|
|
Term
| contraindications to primipexole |
|
Definition
| cimetidine increases t1/2 by 40% |
|
|
Term
|
Definition
anti-viral drug alters dopamine release of uptake (uless mass effect) anticholinergic effects
litte effect on tremor
good gainst rigidity and bradkyinesia |
|
|
Term
|
Definition
|
|
Term
|
Definition
orthostatic hypotension
dry mouth
hallucinations |
|
|
Term
|
Definition
MOA-B is prodominate form in striatum and causes most oxidative metabolism of dopamine that causes harm in parkinsons
low doses do not affect MOA-A bu high doeses will causing severe HTN |
|
|
Term
|
Definition
| severe HTN in high dose due to MOA-A mass effect |
|
|
Term
|
Definition
|
|
Term
| MOA trihexylphenidyl and benstropine |
|
Definition
blocks cholinergic transmission to augment dopamine
modest anti-parkinson action |
|
|
Term
| use of trihexylphenidyl and benstropine |
|
Definition
|
|
Term
| SE trihexylphenidyl and benstropine |
|
Definition
| same as high dose atropine |
|
|
Term
|
Definition
selective inhibitor of COMT (minor enzyme in pathway of levodopa metabolism)
often combined with carbidopa which blocks peripherial decarboxylase and 3-O-methyldopa is formed that competes with levodopa for active transport in the CnS
inhibition of COMT decreases 3-O-methyldopa increasing central levodopa uptake
helps with on-off phenomenon |
|
|
Term
|
Definition
hepatotoxic: measure heptatic enzymes
blood dyscarcies |
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|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
not hepatotoxic
no blood dyscrasias |
|
|
Term
|
Definition
| short acting (administer with ea dose of levodopa/carbidopa) |
|
|
Term
| cause of alzheimers disease |
|
Definition
loss of cortical and subcortical neurons causes dementia
due to b-amyloid causing ROS attack and loss of cholinergic transmission |
|
|
Term
| 3 acetylcholinesterase inhibitors, 1 SE |
|
Definition
tacrin: hepatotoxic
donepezil
rivastigmine |
|
|
Term
| what 2 categories of drugs tx alzheimers disease |
|
Definition
acetylcholinesterase inhibitors
n-methyl-d-aspartate receptor antagonist |
|
|
Term
| what drug is a n-methyl-d-aspartate receptor antagonist |
|
Definition
|
|
Term
|
Definition
overstimulation of NMDA receptors by glytamate lets Ca flow freely into the cell
sustained over exposure of the cells causes cellular degeneration |
|
|
Term
| what symptomatic tx can be used in alzheimers disease |
|
Definition
depression - SSRI (citalopram, paroxetine, sertaline, fluoxetine, edcitalopran)
psychosis/agitation: atypical anti-psychotics (risperidone, olanzapine, queitapine) |
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