Drug Treatment of Movement Disorders Flashcards
(27 cards)
what are the characteristics of neurodegenerative disorders?
- loss of neurons
- progressive
- irreversible
what is palsy?
weakness of the muscles
why is parkinson disease called an akinetic rigid syndrome?
it involves a loss of movement
but increased muscle tone
what is the progression of parkinson’s disease?
slow progression, mild inconvenience at first but becomes worse with time. it is possible to recover control briefly at times of intense emotion like fear2
what is the most common cause of death in parkinson disease patients?
sepsis or bronchopneumonia
symptoms of parkinson disease
tremor
rigidity and limb stiffness, due to an increased muscle tone
speech becomes slurred, monotone, dribbling, dysphagia if late stage
they won’t blink
difficulty initiating and stopping movement
stopping, poor arm swinging, impaired balance
what is the pathology of parkinson disease
loss of neurons in substantial nigra, formation of lewy bodies
dopamine containing neurons affected
what are lewy bodies?
spherical, eosinophilic cells which contain cellular proteins. irritation of these proteins causes the pathology
what are the general approaches to treating parkinson disease?
- increasing dopamine activity
2. decrease ACh activity
how does L-DOPA work?
increases dopamine activity by replacing the lost dopamine
what is the problem with giving L-DOPA?
only 1% of the dose actually reaches the brain, so large doses need to be given in order to have an effect on the CNS
how is this problem solved?
given together with carbidopa - inhibits breakdown of L-DOPA in the blood stream, but does not cross the BBB
what are the adverse effects of giving L-DOPA?
it has an on-off effect - symptoms get worse as the concentration of dopamine drops
nausea and vomiting, anorexia
dyskinesias (excessive movement) due to a very high dose
tachycardia, extrasystoles
hypotension, psychotic effects
side effects increase with time
why does L-DOPA eventually become ineffective?
as the disease progresses, the amount of neurons decrease (up to a net loss of 80%), so dopamine cannot be produced in them
how can the breakdown of existing dopamine be reduced?
inhibit monoamine oxidase, which breaks down dopamine to homovanillinic acid
which MAO inhibitor is used for this purpose?
selegiline
why is selegiline used?
selective MAOb inhibitor, doesn’t affect MAOa receptors, therefore fewer side effects
what are the drawbacks of using selegiline?
effective only in the early stages in the disease, therefore it is given in conjunction with L-DOPA, to prolong the action of L-DOPA
example of a COMT inhibitor
entacapone
what is the benefit of using entacapone?
solves the on-off problem caused by L-DOPA
what are the adverse effects of entacapone?
Aggravate L-DOPA dyskinesias Nausea Diarrhoea Abdo pain Dry mouth effective only in early stages of the disease
how does amantidine work?
increases Dopamine release
useful in early stages, but causes confusion and hallucinations in elderly
examples of dopamine agonists
bromocriptine, pergolide
adverse effects similar to L-DOPA
short half life, so high dose needed
when are antimuscarinics considered?
in young patients with a severe tremor, since it directly targets tremors and drooling
