neurodegenerative drugs

Question 1

PD tx

Answer 1

levadopa
dopamine agonist- bromocriptine, apomorphine
MOA-b inhibitors- selegiline, rasagiline
amantadine
anticholinergics-benztropine, trihexyphenidyl
DBS-subthalamic nucleus or GPi
no atypical antipsychotics (ie halopiridol)

Question 2

HD tx

Answer 2

antipsychotics- haloperidol and tetrabenazipine

juvenile HD parkinsonism- levadopa

Question 3

dystonia tx

Answer 3

anticholinergic-trihexiphenidyl, benztropine
botox
muscle relaxant
DBS GPi

Question 4

L-dopa

Answer 4

tx PD
most efficacious tx for 3-5 years
short 1/2 life
high peripheral metabolite effects
-N/V
-anorexia
-cardiac arrhythmia 
-orthostatic hypotension
CNS AE
-visual/auditory hallucinations 
-dyskinesia
-mood changes: depression, psychosis, anxiety

Question 5

levodopa/carbidopa

Answer 5

PD medication of choice
carbidopa blocks aromatic amino acid decarboxylase
-> 4-5 reduction of levadopa dose
Entacopone/tolcapone- inibits catechol-o-methyltransferase

Question 6

selegiline

Answer 6

PD tx
inhibits monoamine oxidase type B (mitochondrial enzyme)
decreased ROS
adjunctive to levodopa (weak alone)
1/2 life 7-9 hours- helps to mollify levodopa short 1/2 life
metabolized to methamphetamine, and amphetamine
->insomnia

Question 7

rasagiline

Answer 7

rasagiline
inhibits monoamine oxidase type B (mitochondria enzyme)
decrease ROS
adjunctive to levodopa (weak alone)
more selective and more potent than selegiline
not metabolize to amphetamine-> no insomnia

Question 8

apomorphine

Answer 8

PD
dopamine receptor agonist
acute tx of "off periods"
subQ, never IV
AE
-N/V
-arrythmia
-orthostatic hypotension
-sleepiness

Question 9

benztropine, trihexyphenidyl

Answer 9

PD tx
-tremor and rigidity (not bradykinesia)
muscarinic antagonist
-blocks overtimulation of muscarinic receptor in PD (indirect pathway)
AE
-blurred vision            -delerium
-dry mouth                 -psychosis
-urinary retention       -memory
-constipation
-glaucoma

Question 10

amantadine

Answer 10

PD tx
-bradykinesia and rigidity (not tremor)
used prior to L-dopa-> put off its wear off time, prolong tx
increases DA release, blocks cholinergic and GLUinergic NMDA rec
AE
-hallucination and confusion
-dizziness
-LE rash
-contraindicated in CHF and glaucoma

Question 11

donepezil, galantamine, rivastigmine, tacrine

Answer 11

AZ tx
ACHEi
modest improvement
rivastigmine-> no CYP interaction
AE
-tremors
-bradycardia
-N/V
-diarrhea
-anorexia
-tacrine-> hepatoxicity

Question 12

memantine (Namenda)

Answer 12

AZ tx
NMDA receptor antagonist-> blocks toxic Ca influx
improves daily activities and cognitive faculty
additive with donepezil
AE
-dizziness
-HA
-constipation
-confusion, agitation

Question 13

essential tremor tx

Answer 13

beta blockers- propranolol
seizure drugs- primidome, gabapentin, topiramate
benzo- clonazepam
DBS-thalamic

Question 14

bromocriptine

Answer 14

d2 agonist and d1 partial agonist
used mono or with L-DOPA
contraindicated in heart disease or mental problem
AE
arrythmias, orthostatic hypotension, N/V
hallucination, depression, confusion, sleepy impulsive

Question 15

Ropinirole, Pramipexole

Answer 15

d2 and d3 agonist
used mono or with L-DOPA
contraindicated in heart disease or mental problem
AE
arrythmias, orthostatic hypotension, N/V
hallucination, depression, confusion, sleepy impulsive