17- Neurodegeneratives Flashcards
levodopa (L-DOPA)
ENHANCER of DA synthesis
- used in Parkinson’s Disease (oral)
- precursor of DA that is able to cross BBB
- dec. rigidity, tremors, and other PD symptoms
- “wearing off” effect in 3-5 years
- short half-life, 1-2 hrs
- only 1-3% reaches the brain, rest is metabolized by AAAD in periphery
- peripheral s/fx caused by conversion of L-DOPA to DA to NE (anorexia, tachycardia, nausea, hypotension)
- CNS s/fx: depression, hallucinations, psychosis, anxiety
L-DOPA/carbidopa (Sinemet)
ENHANCER of DA synthesis
- medication of choice in Parkinson’s Disease
- carbidopa is AAAD inhibitor which blocks peripheral metabolism of L-DOPA (reduce dose 4-5x)
- reduces peripheral s/fx
entacapone/L-DOPA/carbidopa (Stalevo)
ENHANCER of DA synthesis
- used in Parkinson’s Disease
- entacapone inhibits COMT which metabolized L-DOPA to 3-OMD (toxic metabolite) in periphery
- further inc. levels of L-DOPA that reach the brain
apomorphine (Apokyn)
dopamine receptor AGONIST
- used in Parkinson’s Disease
- acute tx of pts with advanced disease- “off periods”
- administered sub-q, NOT IV (thromboembolism risk)
- S/FX: N/V, arrhythmias, post. hypotension, hallucinations, pronounced sleepiness
bromocriptine (Parlodel)
dopamine receptor AGONIST
- used in Parkinson’s Disease (orally active)
- D2 receptor agonist, D1 receptor partial agonist
- monotherapy in early stages, adjunct in late stages
- need to begin with low dose and titrate up slowly
- S/FX: arrhythmias, post, hypotension, depression, hallucinations, impulsivity, N/V
- contraindicated in those with heart or mental problems
pramipexole (Mirapex)
dopamine receptor AGONIST
- used in Parkinson’s Disease (orally active)
- D2 and D3 agonist
- monotherapy in early stages, adjunct in late stages
- need to begin with low dose and titrate up slowly
- S/FX: arrhythmias, post, hypotension, depression, hallucinations, impulsivity, N/V
- contraindicated in those with heart or mental problems
ropinirole (Requip)
dopamine receptor AGONIST
- used in Parkinson’s Disease (orally active)
- D2 and D3 agonist
- monotherapy in early stages, adjunct in late stages
- need to begin with low dose and titrate up slowly
- S/FX: arrhythmias, post, hypotension, depression, hallucinations, impulsivity, N/V
- contraindicated in those with heart or mental problems
amantadine (Symmetrel)
misc. Parkinson’s treatment
- blocks muscarinic signaling, moderately inc. DA release, and blocks glutamate NMDA receptors
- alleviates BRADYKINESIA and rigidity prior to initiation of L-DOPA
- S/FX: hallucinations/confusion, nausea, dizziness, rash, antimuscarinic effects
benzotropine (Cogentin)
anticholinergic- muscarinic antagonist
- used in PD
- blocks muscarinic overstimulation that occurs with ACh neuron that over fires d/t lack of inhibition by DA
- alleviates TREMORS and rigidity as monotherapy or in combo
trihexyphenidyl (Artane)
anticholinergic- muscarinic antagonist
- used in PD
- blocks muscarinic overstimulation that occurs with ACh neuron that over fires d/t lack of inhibition by DA
- alleviates TREMORS and rigidity as monotherapy or in combo
rasagiline (Azilect)
MAOb Inhibitor
- used in PD treatment (orally active)
- adjunctive treatment to L-DOPA
- dec. production of hydrogen peroxide and free radicals
- NOT metabolized to methamphetamine and amphetamine
selegiline (L-Deprenyl)
MAOb Inhibitor
- used in PD treatment (orally active)
- adjunctive treatment to L-DOPA
- dec. production of hydrogen peroxide and free radicals
- half-life 7-9 hrs, excreted renally
- metabolized to methamphetamine and amphetamine leading to insomnia
donepezil (Aricept)
AChE Inhibitor
- used in Alzheimer’s Disease
- blocks ACh catabolism leading to inc. synaptic levels and inc. ACh signaling
- modest improvement in cognition for some patients
- good oral bioavailability
- metabolized by P450 liver enzymes (CYP3A4, CYP2D6)
galantamine (Reminyl)
AChE Inhibitor
- used in Alzheimer’s Disease
- blocks ACh catabolism leading to inc. synaptic levels and inc. ACh signaling
- modest improvement in cognition for some patients
- good oral bioavailability
- metabolized by P450 liver enzymes (CYP3A4, CYP2D6)
rivastigmine (Exelon)
AChE Inhibitor
- used in Alzheimer’s Disease
- blocks ACh catabolism leading to inc. synaptic levels and inc. ACh signaling
- modest improvement in cognition for some patients
- good oral bioavailability
- metabolized by plasma cholinesterase
