DRUGS AFFECTING THE CNS Flashcards
when do the symptoms of PD start appearing?
when 70-80% of dopamine neurones die
what is the cause of muscle ridgity and akinesia in PD?
loss of nigrostriatal efferents causes:
- lack of the direct pathway
- increase in the indirect pathway
both due to loss of dopamine
what is the cause of the resting tremor in PD?
disinhibition of intrinsic cholinergic neurones in the striatum,
the striatum has GABA projection to these neurones, but when dopamine is loss these projections which are activated via dopamine no longer work
what is the dopamine pathway that fails in PD?
A9 nucleus –> striatum
what are the two dopamine pathways involved in pyschosis?
A10 –> nucleus accumbens (mesolimbic pathway)
A10 –> frontal cortex (mesocortical pathway)
what dopamine pathway is involved in inhibition of prolactin secretion?
median eminence –> anterior pituatory
how is dopamine linked to nausea
dopamine activates the chemotrigger zone, thereby inducing emesis
how does L dopa work? what should be used with it
what symptoms does it best work to improve?
L dopa is the precusor form of dopamine (it is used because dopamine cannot cross the blood - brain barrier)
converted to dopamine via dopa decarboxylase
should be used with a dopa decarboxylase inhibitor carbidopa
best works to improve the symptoms of akinesia and ridgity but not tremor
how well does L-DOPA work?
works best in less elderly patients improvement seen for first 18months of treatment, then maintained improvement for 2-3 years then decline (due to death of neurones)
what are the side effects of LDOPA?
central: - dyskinesia - pyscotic effects reduction in prolactin release on-off effects -- those effects are seen with prolonged use of L-DOPA, and they cause uncontrolled swings between akinesia and dyskinesia - causing loss of smooth motor control
peripherial effects:
- hypotension
- nausea
How does carbidopa work in PD? why is it used?
carbidopa is a dopa decarboxylase inhibitor, it prevents the peripheral conversion of LDOPA –> dopamine, thereby reducing the peripheral side effects of dopamine
carbidopa remains in the periphery, because cannot cross the blood brain barrier
it allows faster and smoother onset of LDOPA
what is selegiline?
a MAO-B inhibitor
prevents the breakdown of dopamine into its metabolites
allows more effective therapy and also seems to reduce to onset of the progression of the disease
what are the dopamine receptor agonists used in PD treatment?
what is a major problem with them that patients should be warned about?
non-ergot alkaloid agonists (preferred)
-ropinirole
ergot alkaloid agonist:
- bromocriptine
- effective in elderly where L -DOPA is no longer effective
apomorphine:
- D1 and D2 receptor agonist by refractory
patients should be warned by impulse control disorders, because dopamine is a major transmitter in the rewards systems side effects include: - gambling - hypersexuality - shopping
what is domperidone? why is it used in PD>
it is a D2 receptor antagonist
must be used with Dopamine agonists, to reduce the nausea
the CTZ is located in the brain stem, but does not have a blood brain barrier -
why are muscuranic antagonists used in PD? why should it be avoided?
give examples
examples atropine and benzhexol
used because:
- to antagonise the excess cholinergic activity in the basal ganglia which causes resting tremor
the drugs only work to reduce the resting tremor, but have no affect on the akinesia or muscle ridigity
however, its use should be avoided because it will lead to decline in cognitive function
