Neurodegenerative Disease

Question 1

Riluzole

Answer 1

ALS; complex pre and post synaptic mechanism: inhibits GLU release, inhibits NMDA and kainite GLU receptors; inhibits fast Na+ channels (slight effect to slow disease progression 2-3 months)

Question 2

Edaravone

Answer 2

ALS; mechanism unclear, no benefit advanced cases, may slow in early disease, IV dosing

Question 3

Baclofen

Answer 3

GABAb agnoist - acts in spinal cord inhibit motoneurons (palliative ALS); skeletal muscle relaxant

Question 4

Tizansidine

Answer 4

alpha2 agonist; CNS to decrease muscle tone palliative ALS also skeletal muscle relaxant

Question 5

Dextromethorphan

Answer 5

Pseudobulbar affect in ALS; complex MOA: agnoist at sigma receptor, weak inhibition of 5-HT transporter; allosteric inhibition of NMDA

Question 6

Quinidine

Answer 6

reduced dextromethorphan metablism so acts longer (by CYP2D6)

Question 7

L-DOPA/Carbidopa

Answer 7

LDOPA DA precursor enters CNS via AA transporter (neutral), enters DA neurons, converted to DA by DOPA decarboxylase (nausea, vomiting); Carbidopa does not penetrate CNS, keeps L DOPA from converting to DA in periphery

Question 8

DA Receptor Agonists

Answer 8

Parkinson’s less motor recovery and more side effects than L DOPA but less risk of dyskinesias (nausea, vomiting, psychiatric rxns, postural hypotension)

Question 9

Bromocriptine

Answer 9

obsolete ergot DA receptor agonist

Question 10

Pramipexole

Answer 10

renal clearance; non ergot DA receptor agonist also approved for sudden restless leg syndrome. D2 agonists can impair impulse control, lead to excessive gambling, shopping, food intake, sexual activity etc

Question 11

Ropinirole

Answer 11

hepatic clearance; non ergot DA receptor agonists; can impair impulse control

Question 12

Rotigitine

Answer 12

24 hr transdermal patch DA receptor agonist

Question 13

apomorphine

Answer 13

non ergot DA receptor agonist injected s.c. rapid but temp relief of off akinesia episodes; nausea common

Question 14

trimethobenzamide

Answer 14

pretreat nausea of apomorphine, antiemetic

Question 15

MAO-B inhibitors

Answer 15

minor effects for Parkinson’s alone but enhance L DOPA effects

Question 16

Selegiline

Answer 16

MAO B inhibitor; metabolites include methaphetamine and amphetamine - insomnia anxiety. minor effects for Parkinson’s alone but enhance L DOPA effects

Question 17

Rasagline

Answer 17

MAO B inhibitor; minor effects for Parkinson’s alone but enhance L DOPA effects

Question 18

COM-T inhibitors

Answer 18

peripheral action only, enhances L DOPA by blocking converstion to 3-O methylDOPA

Question 19

Entacapone

Answer 19

COM-T inhibitor peripheral action only, enhances L DOPA by blocking converstion to 3-O methylDOPA

Question 20

antimuscarnics

Answer 20

parkinsons - improve tremor and rigidity, little effect on bradykineseia (poorly tolerated effects in eldery)

Question 21

benztropine

Answer 21

antimuscarinic improve tremor and rigidity

Question 22

trihexiphenidyl

Answer 22

antimuscarinic - improve tremor and rigidity

Question 23

diphenhydramime

Answer 23

antimuscaranic - improve tremor and rigidity

Question 24

Amantidine

Answer 24

enhances DA release but short-lived (weeks to months) improves most aspects of motor control for this time; unique ability to decrease L DOPA induced dyskinesias

Question 25

Stalevo

Answer 25

combination of entacopone (COMT inhibitor) LDOPA and Carbidopa helpful in severe disease with on-off fluctuations

Question 26

Safinamide

Answer 26

New MAO B inhibitor for decreasing off episodes in late stage Parkinsons. Also has effects to block Na+ channels and reduce Glutamate release

Question 27

Pimavaserin

Answer 27

new 5HT2A and 5-HT2C receptor antagonsit/inverse agonist reduce hallucinations and delusions that often complicate late stage PD

Question 28

Anticholinesterase

Answer 28

AD tx: address loss of cholinergic pathway (nucleus of basalis of Meynert) to cortex

Question 29

Donepezil

Answer 29

moderate and severe disease; anticholinesterase for AD; inverse U dose response curve

Question 30

Rivastigmine

Answer 30

(Transdermal) anticholinesterase for AD inverse U dose response curve; moderate disease

Question 31

Galantamine

Answer 31

anticholinesterase for AD inverse U shaped dose response curve; moderate disease

Question 32

Memantine

Answer 32

weak NMDA receptor negative allosteric modulator (GLU); Alzheimers, combo with donepezil available now to tx AD

Question 33

Bapineuzumab

Answer 33

humanized monoclonal antibody to AB (alzheimer's); reduces plaque but not cognitive protection

Question 34

Aducanumab

Answer 34

monoclonal antibody for AB in AD showed decrease in rate of progression of cognitive impairment as well as reduction in plaques

Question 35

Haloperidol and Fluphenazine

Answer 35

1st gen antipsychotics blocking D2 receptors for Huntingtons

Question 36

Olanzepine

Answer 36

2nd gen antipsychotic block D2 receptor Huntington

Question 37

VAMT2 inhibitors

Answer 37

block storage of DA and other monoamines in secretory vesicles (huntingtons)

Question 38

Tetrabenazine

Answer 38

VAMT2 inhibitor Huntingtons

Question 39

Duetetrabenazine

Answer 39

VAMT2 inhibitor Huntingtons

Question 40

Reserpine

Answer 40

VAMT2 inhibitor Huntingtons