Mnpc Ii Exam 4- Pd

Front 1

spasticity disorders- often accompanies what disorders (4)

Back 1

accompanies disorders such as cerebral palsy, MS, spinal cord injury stroke

Front 2

definition of spasticity disorder- sx (3)

Back 2

increase in tonic stress reflexes & flexor muscle spasms

muscle weakness

Front 3

clinical triad of of PD signs (3)

plus one extra

Back 3

resting tremor
rigidity
bradykinesia

maybe dementia

Front 4

PD targets what neuro pathway?

Back 4

slowly progressive, neurodegenerative disorder of Extrapyramidal DA nigrostriatial pathway

Front 5

area of brain primarily affected by PD (1 general, one specific area)

Back 5

basal ganglia: pars compacta substantia nigra

Front 6

5 nuclei of basal ganglia affected by PD

Back 6

straitum (caudate/putamen)
globus pallidus
subthalamic nuc
substantia nigra pars compacta
SN pars reticulata

Front 7

indirect vs direct pathway- listen

Back 7

indirect vs direct pathway- listen

Front 8

PD effect on direct and indirect pathway (3)

Back 8

in PD, indirect pathway is increased
-results in inhibition of movement
-direct pathway neurons are dmged, so indirect becomes dominant

Front 9

3 theories for PD etiology

Back 9

proteolytic stress

genetics (alpha synuclein/parkin mutations)

dopamine oxidation

Front 10

proteolytic stress theory (3)

Back 10

endogenous neurotoxicants
mitochondrial distress
oxidative metabolism

these 3 things lead to oxidative stress

Front 11

3 genes assoc with familiar PD

Back 11

DJ-1, PINK1, LRRK2

Front 12

ROS etiology of PD (3 steps)

Back 12

generation of H2O2 and NH3 from terminal amines on proteins + O2 + H2O (equ 1)

H2O2 + O2 = ROS

ROS attacks DA-->semiquinone-->quinone- attacks everything

Front 13

chemical that induces PD and it's toxic metabolite

Back 13

MPPP (designer heroin) -->MPTP

MPP...is neurotoxic

Front 14

5 ways to treat PD

Back 14

1) augment synth of DA
2) stimulate DA release
3) directly stimulate receptors (DA agonist)
4) decrease DA reuptake
5) decrease DA catabolism

Front 15

most effective therapy for PD

Back 15

levodopa

Front 16

levodopa- how does it work

Back 16

decarboxylated into DA in CNS (DA can't get in, but levodopa can)

Front 17

4 AE of levodopa

Back 17

gastric upset- n/v
activation of peripheral DA receptors and adrenergic receptors = vasoconstriction

after 5 years, 50% of pt develop more fluctuations?

drug resistance after 15 years of therapy

Front 18

AE of levodopa at higher doses (3)

Back 18

higher doses = mania, psychosis, hallucinations

Front 19

side fx of levodopa minimized by what?

Back 19

side fx minimized by carbidopa?

Front 20

2 MAO-B inhibitors for PD

Back 20

R-(+)-rasagiline
R-(-)selegiline

Front 21

selegiline vs rasagiline

Back 21

selegiline metabolites can be amphetamines and have CV/psych AE

rasagiline dose not

Front 22

usage of selegiline/rasagiline and what are they

Back 22

selectiveMAO-B inhibitors used with levopdopa to prolong duration

Front 23

benefits of using selegiline/rasagiline

Back 23

has beneficial effect on motor fluctuations

Front 24

metabolism of selegiline/rasagiline

Back 24

extensive liver metabolism

Front 25

COMT inhibitors (2)

Back 25

tolcapone
entacapone

Front 26

tolcapone/entacapone- purpose/effect

Back 26

blocks COMT-->preserves DA and levodopa activity

Front 27

tolcapone vs entacapone - toxicity/usage

Back 27

tolcapone is hepatotoxic so mostly use entacapone

Front 28

COMT inhibitors- main AE

Back 28

increased dyskinesia- monitor

Front 29

amantadine
memantine MoA

3

Back 29

DA release promoters
DA reuptake inhibitors
NMDA receptor antagonists- prevent excessive influx of Ca++ into neuronal cells (excitotoxicity)- may be neuroprotective

Front 30

DA receptor agonists require nerve terminals?

Back 30

do not require functional DA nerve terminals because they stimulate DA receptors directly

Front 31

which receptor is targeted clinically (and type of agonist used) for DA agonists?

Back 31

primarily D2 receptors (full or partial) agonists are used clinically

Front 32

DA receptor agonists- mono or combo therapy? monotherapy can be used in whom?

Back 32

usually used in combo with levo/carbi

monotherapy often used in younger, more tolerant pt (can reach higher doses i guess)

Front 33

D1 like receptors (2)

coupled to what

Back 33

D1 and 5- stimulatory DA receptors

coupled to Galpha(s) (increases cAMP)

Front 34

D2 like receptors (3)

coupled to what

Back 34

D2, 3, 4

inhibitory DA receptors coupled to Gai/o (decreases cAMP)

Front 35

4 DA agonists

Back 35

bromocriptine
pergolide
ropinirole
s-pramipexole

Front 36

bromocriptine- derived from?

target receptors (and agonist action) (2)

dosing

Back 36

ergot peptide derivative

full agonist at D2 receptor
partial agonist at D1 receptor (direct pathway)

given at higher doses: 10-20 mg/day

Front 37

pergolide- structure/type of molecule

target receptors and agonist action at both
(compare to bromocriptine)

Back 37

NON-PEPTIDE ergot derivative

higher potency/efficacy as D1 agonist
equivalent D2 agonist activity
(these are both compared to bromocriptine)

Front 38

pergolide usage

Back 38

used as pt become tolerant to bromocriptine (due to higher potency)

Front 39

ropirinole/parmipexole- target receptors and activity at each (3)

Back 39

full agonists SELECTIVE for D2/D3

NO ACTIVITY at D1- this is unique

Front 40

usage of ropirinole/pramipexole- when to use, why (2)

Back 40

treatment of early PD as monotherapy or with levo/carbi

slower decline reported than with levodopa- so use levodopa first, then switch to ropirinole/pramipexole

Front 41

SAR

Back 41

---listen