Pharma of Neurodegen Diseases Flashcards
2 Meds for cognitive impairment
- cholinesterase inhibitors
- NMDA receptor antagonist
Mechanism of action of cholinesterase inhibitors
-block the breakdown of ACh at the synaptic cleft => more ACh available to postsynaptic receptors => net increase in cholinergic fxn
Indications for cholinesterase inhibitors
- Alzheimer’s disease
- Parkinson’s disease dementia
- Lewy body dementia
Main side effect of cholinesterase inhibitors
GI: N/V, diarrhea, cramps
Mechanism of action of NMDA receptor antagonist
- noncompetitive NMDA receptor antagonist
- may reduce abnormal glutamatergic activity
Indication for NMDA receptor antagonist
Alzheim’ers disease
Side effects of Memantine
Memantine = NMDA receptor antagonist
Side effects: dizziness, headache, confusion, constipation
Parkinsons
(a) direct pathway
(b) indirect pathway
(c) overall mechanism
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
What are the two classes of PD medications?
Dopmainergic and non-dopaminergic
Go to medication treatment for PD
L-DOPA (Levodopa)
Mechanism of Levodopa
L-DOPA = DA precursor, converted to DA in the brain
How dopamine agonist side effects are minimized
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
Two benefits of carbidopa
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
Side effects of taking levodopa alone
(a) conversion to dopamine in the periphery => nausea and vomiting
(b) lower levodopa gets to the brain => little symptomatic benefit
What is sinemet?
Sin (without) + emet (vomit)
= Carbidopa/Levodopa combo => get the sympatomatic benefit for PD w/o the nausea/vomiting side effects
Side effects of L-DOPA
- nausea/vomiting
- sleepiness
- hallucinations
- orthostatic hypotension
Two motor complications of levodopa
- wearing off phenomenon: levels fluctuate so below therapeutic threshold for a lot of the time
- dyskinesias = abnormality or impairment of voluntary movement
What movement disorder can Levodopa treatment cause
Levodopa-induced dyskinesias
- abnormal involuntary movements
- often choreiform (dance-like movements)
- occurs w/ long term use of DOPA
Mechanism of dopamine agonists
Bind directly to dopmaine receptors to directly stimulate both postsynaptic and presynaptic dopamine receptors
Two advantages of dopamine agonists over levodopa
- less wearing off
- less dyskinesias
Advantages of levodopa over dopamine agonists
- 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
What medication is ‘sleep attacks’ associated with?
Dopamine agonists
