Tuesday 1 - slattery - basal ganglia Flashcards
Back up for a second
What is the basal ganlgia and what is it’s function?
Basal ganglia consists of the Striatum, Globus pallidus (internal and external), the sub thalamic nucleus, and the thalmus
It’s funtion is to regulate motor output i.e. relaxing your biceps while you contract your triceps so that you can extend your arm
What is released by the Subthalamic nucleus? What does it stimulate
glutamate
globus pallidus interna
Hypokinetic disorder and an example
direct basal ganglion pathway inhibited or indirect activated
less motor activity
parkinsons
Hyperkinetic disorder and example
Direct pathway active and or indirect inhibited
more motor activity
huntingtons
What happens in parkinsons
progressive death and loss of dopanergic neurons (these neurons release dopamine)
Sx of parkinsons
bradykinesia - slowness of movement
muscle rigidity
resting tremor
impaired postural balance
L-dopa mech and side effects
pro-drug
emmediate metabolic precursor of dopamine
crosses BBB by and amino acid transporter
enzymatically converted into dopamine by L-aromatic amino acid decarboxylase (AAAD)
side effects: AAAD decarboxylase activity is also in the GI tract, dopamine causes nausia in periphery
can cause dystonia if dosage is not constant or is too high
Carbadopa
mech
inhibits l-aromatic amino acid decarboxylate (AAAD) and doesn’t cross BBB
reduces L-dopa in periph to reduce nausia and side effects
levodopa + carbidopa =
sinemet
most significant side effect of l-dopa
dyskinesia, usually:
peak dose or “on” period dyskinesia
abnormal involuntary movements
usually upper limbs
dyskinesia that effects the lower limbs
diphasic dyskinesia - appears with rising and falling of dopamine levels
what happens when your l-dopa is low
off period dystonia
fixed and painful postures more frequently effecting the feet
on - off phenomenon
sudden and rapid waxing and waning of l-dopa
where else besides the striatum do you find dopamine receptors?
diseases associated with them
limbic system and frontal cortex - schizophrenia
brainstem - chemoreceptor trigger zone (nausia and vomiting just like in GI tract) (outside BBB)
all adverse effects of l-dopa
confusion, anxiety, agitation, insomnia, nightmares, depression, schizophrenic like delusions and hallucinations
COMT inhibitors mech
example of drug name
catechol-O-methyltransferase
decrease peripheral metabolism of l-dopa by inhibition of l-aromatic amino acid decarboxylase (it competes with AAAD by binding l-dopa and making an inactive, excretable substance
smooths on/off fluctuation
entacapone
MAOI mech of ones that are used for parkinsosn
example of drug name
MAO-b: primarily metabolizes dopamine
smooths on/off fluctuation
selegiline
2 dopamine receptor agonists*
all examples work on D2 receptors
used more commonly now
reduces on/off fluctuations
*pramipexole - D3 (a type of D2 receptor)
ropinirole - D2
muscarinic antagonist drugs used coloquially for parkinsons
just the mech
aka anticholineargic (inhibit release of ACh)
Huntington’s disease
hyperkinetic disorder, uncontrolled jerking
decreased control of the indirect pathway
Name for bried, abrupt, unpredictable stereotyped movements
chorea, seen in huntinton’s disease
