Tuesday 1 - slattery - basal ganglia

Question 1

Back up for a second

What is the basal ganlgia and what is it’s function?

Answer 1

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

Question 2

What is released by the Subthalamic nucleus? What does it stimulate

Answer 2

glutamate

globus pallidus interna

Question 3

Hypokinetic disorder and an example

Answer 3

direct basal ganglion pathway inhibited or indirect activated

less motor activity

parkinsons

Question 4

Hyperkinetic disorder and example

Answer 4

Direct pathway active and or indirect inhibited

more motor activity

huntingtons

Question 5

What happens in parkinsons

Answer 5

progressive death and loss of dopanergic neurons (these neurons release dopamine)

Question 6

Sx of parkinsons

Answer 6

bradykinesia - slowness of movement

muscle rigidity

resting tremor

impaired postural balance

Question 7

L-dopa mech and side effects

Answer 7

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

Question 8

Carbadopa

mech

Answer 8

inhibits l-aromatic amino acid decarboxylate (AAAD) and doesn’t cross BBB

reduces L-dopa in periph to reduce nausia and side effects

Question 9

levodopa + carbidopa =

Answer 9

sinemet

Question 10

most significant side effect of l-dopa

Answer 10

dyskinesia, usually:

peak dose or “on” period dyskinesia

abnormal involuntary movements

usually upper limbs

Question 11

dyskinesia that effects the lower limbs

Answer 11

diphasic dyskinesia - appears with rising and falling of dopamine levels

Question 12

what happens when your l-dopa is low

Answer 12

off period dystonia

fixed and painful postures more frequently effecting the feet

Question 13

on - off phenomenon

Answer 13

sudden and rapid waxing and waning of l-dopa

Question 14

where else besides the striatum do you find dopamine receptors?

diseases associated with them

Answer 14

limbic system and frontal cortex - schizophrenia

brainstem - chemoreceptor trigger zone (nausia and vomiting just like in GI tract) (outside BBB)

Question 15

all adverse effects of l-dopa

Answer 15

confusion, anxiety, agitation, insomnia, nightmares, depression, schizophrenic like delusions and hallucinations

Question 16

COMT inhibitors mech

example of drug name

Answer 16

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

Question 17

MAOI mech of ones that are used for parkinsosn

example of drug name

Answer 17

MAO-b: primarily metabolizes dopamine

smooths on/off fluctuation

selegiline

Question 18

2 dopamine receptor agonists*

Answer 18

all examples work on D2 receptors

used more commonly now

reduces on/off fluctuations

*pramipexole - D3 (a type of D2 receptor)
ropinirole - D2

Question 19

muscarinic antagonist drugs used coloquially for parkinsons

just the mech

Answer 19

aka anticholineargic (inhibit release of ACh)

Question 20

Huntington’s disease

Answer 20

hyperkinetic disorder, uncontrolled jerking

decreased control of the indirect pathway

Question 21

Name for bried, abrupt, unpredictable stereotyped movements

Answer 21

chorea, seen in huntinton’s disease