Pharma of Neurodegen Diseases

Question 1

2 Meds for cognitive impairment

Answer 1

• cholinesterase inhibitors

- NMDA receptor antagonist

Question 2

Mechanism of action of cholinesterase inhibitors

Answer 2

-block the breakdown of ACh at the synaptic cleft => more ACh available to postsynaptic receptors => net increase in cholinergic fxn

Question 3

Indications for cholinesterase inhibitors

Answer 3

• Alzheimer’s disease
• Parkinson’s disease dementia
• Lewy body dementia

Question 4

Main side effect of cholinesterase inhibitors

Answer 4

GI: N/V, diarrhea, cramps

Question 5

Mechanism of action of NMDA receptor antagonist

Answer 5

• noncompetitive NMDA receptor antagonist

- may reduce abnormal glutamatergic activity

Question 6

Indication for NMDA receptor antagonist

Answer 6

Alzheim’ers disease

Question 7

Side effects of Memantine

Answer 7

Memantine = NMDA receptor antagonist

Side effects: dizziness, headache, confusion, constipation

Question 8

Parkinsons

(a) direct pathway
(b) indirect pathway
(c) overall mechanism

Answer 8

Parkinsons

(a) Less activation of basal ganglia’s direct pathway
(b) Less inhibition of basal ganglia’s indirect pathway
(c) Overall: dopamine deficiency in the substantia nigra inhibits movement

Question 9

What are the two classes of PD medications?

Answer 9

Dopmainergic and non-dopaminergic

Question 10

Go to medication treatment for PD

Answer 10

L-DOPA (Levodopa)

Question 11

Mechanism of Levodopa

Answer 11

L-DOPA = DA precursor, converted to DA in the brain

Question 12

How dopamine agonist side effects are minimized

Answer 12

L-DOPA: goal is to have it be converted in the brain only (not in the periphery) b/c it is in the periphery where it will cause side effects

-accomplish this by taking dopa decarboxylase inhibitor to prevent levodopa conversion to DA in the periphery

Question 13

Two benefits of carbidopa

Answer 13

L-dopa always given with carbidopa (dopa decarboxylase inhibitor) to prevent peripheral conversion => decrease side effects

Other benefit = greater sympatomatic benefit since more L-DOPA gets into the brain

Question 14

Side effects of taking levodopa alone

Answer 14

(a) conversion to dopamine in the periphery => nausea and vomiting
(b) lower levodopa gets to the brain => little symptomatic benefit

Question 15

What is sinemet?

Answer 15

Sin (without) + emet (vomit)

= Carbidopa/Levodopa combo => get the sympatomatic benefit for PD w/o the nausea/vomiting side effects

Question 16

Side effects of L-DOPA

Answer 16

• nausea/vomiting
• sleepiness
• hallucinations
• orthostatic hypotension

Question 17

Two motor complications of levodopa

Answer 17

• wearing off phenomenon: levels fluctuate so below therapeutic threshold for a lot of the time
• dyskinesias = abnormality or impairment of voluntary movement

Question 18

What movement disorder can Levodopa treatment cause

Answer 18

Levodopa-induced dyskinesias

• abnormal involuntary movements
• often choreiform (dance-like movements)
• occurs w/ long term use of DOPA

Question 19

Mechanism of dopamine agonists

Answer 19

Bind directly to dopmaine receptors to directly stimulate both postsynaptic and presynaptic dopamine receptors

Question 20

Two advantages of dopamine agonists over levodopa

Answer 20

• less wearing off

- less dyskinesias

Question 21

Advantages of levodopa over dopamine agonists

Answer 21

• levodopa more effective
• dopamine agonists: more orthostatic hypotension, psychosis, daytime sleepiness
• dopamine agonists: ‘sleeping attacks’ = falling asleep w/o warning
• pedal edema
• impulse control disorder

Question 22

What medication is ‘sleep attacks’ associated with?

Answer 22

Dopamine agonists