Lecture 8 - Parkinson's and HD and drugs

Question 1

Parkinson Disease (PD):
symptoms = TRAPS

Answer 1

Tremor (Resting);
Rigidity (cogwheel);
Akinesia
Postural Instability;
Shuffling gait

Question 2

PD:
loss of ____ neurons in the ______.
increased or decreased pigmentation?

Answer 2

dopaminergic;
substantia nigra pars compacta (SNpc);
decreased

Question 3

PD:

_____ dementia, ____ face

Answer 3

late-onset;

expressionless

Question 4

PD:
lewy bodies composed of ____;
intra or extracellular?

Answer 4

alpha-synuclein;

intracellular

Question 5

PD enviornmental exposures:
_____, a contaminant in illegal drugs is associated.
_____, a pesticde.
others; generally, these inhibit ____ function and trigger ___ stress

Answer 5

MPTP;
rotenone
mitochondrial, oxidative

Question 6

basal ganglia:
direct pathway (excitatory or inhibitory?).
cortical inputs stimulate the striatum = increased release of \_\_\_\_\_ which inhibits \_\_\_\_ release from the \_\_\_\_. = disinhibits the \_\_\_\_\_ = \_\_\_\_\_ motion

Answer 6

excitatory;
GABA, GABA, GPi;
thalamus, increased

Question 7

basal ganglia pathway:
indirect (inhibitor or excitatory?)
1. striatum releases ____ that disinhibits the _____ via ____ inhibition.

Answer 7

GABA, STN, GPe

Question 8

indirect pathway

2. The STN ______ _____ to inhibit the thalamus = ____ motion

Answer 8

stimulates GPi;

decreased

Question 9

Dopamine/striatum:
dopamine binds D1 = _____ the ____ pathway
binds D2 = ____ the ____ pathway
overall = ____ motion

Answer 9

stimulating, excitatory/direct;
inhibiting the inhibitory/indirect;
increase

Question 10

what makes up the striatum?

Answer 10

putamen and caudate

Question 11

in PD:

dopamine is ____. Ach is _____

Answer 11

decreased, increased

Question 12

2 antimuscarinics used in PD:
____, ____.
these improve _____; little effect on _____

Answer 12

benztropine, tihexyphenidyl;
tremor/rigidity;
bradykinesia

Question 13

Levodopa/L-dopa:

converted by _____ to _____ in the brain. peripheral side effects include ______, _____ (heart), and ______ (CNS)

Answer 13

dopa decarboxylase, dopamine;
GI probs, arrythmias;
behavior changes (ie anxiety, psychosis)

Question 14

carbidopa:
mechanism of action?
increases _____ in regards to L-dopa

Answer 14

peripheral dopa decarboxylase inhibitor;

oral bioavailability/action

Question 15

long term L-dopa use prbs:
“___” phenomena, with alternating akinesia and ____;
“_____” phenomenon, several hours after dose.
can alleviate symptoms by administering L-dopa in a ____ manner

Answer 15

on-off, dyskinesia (ie choreoatheosis);
end of dose;
continuous (vs pulsatile)

Question 16

____ is a D1/D2 agonist. administed in late-stage PD, but is a potent ____

Answer 16

apomorphine;

emetic

Question 17

2 ergolines/dopamine receptor agonists that aren’t used much

Answer 17

bromocriptine, pergolide

Question 18

dopamine agonists: ____ is a D2 agonist. ____ is a D3 agonist. used in early or late stage PD?

Answer 18

ropinirole, pramipexole;

early

Question 19

selegiline (and rasagiline) inhibits ____, which is selective for _____

Answer 19

MAO-B;

dopamine

Question 20

entacapone and tolcapone are ____ inhibitors. which works peripherally and which works in the CNS?

Answer 20

COMT;
both work peripherally,
tolcapone also works centrally

Question 21

entacapone and tolcapone increase ______

Answer 21

duration of effect; ie not potency

Question 22

Huntington’s Disease (HD):

decreased ____ causes _____ inhibition of movement

Answer 22

GABA, decreased

Question 23

HD:
atrophy of ____.
____ repeats.
inheritance?

Answer 23

caudate;
CAG;
autosomal dominant (Complete penetrance :()

Question 24

HD treatment:
_____ which inhibits VMAT = decreased ____ vesicle packaging and release
____ (antipsychotic)

Answer 24

tetrabenazine (or reserpine);
dopamine;
haloperidol