Neurodegenerative Disorders Flashcards
tacrine (Cognix)
donepezil (Aricept)
galantamine (Reminyl)
rivastigmine (Exelon)
Treatment of Alzheimer’s
Cholinesterase inhibitors
MOA: inhibit AchE in basal forebrain–>increase Ach
Side effects: diarrhea, nausea, vomiting, insomnia, anorexia (weight loss)
Tacrine not used much because requires 4 doses/day (not ideal for person with memory loss)
Drug interactions: avoid drugs with anticholinergic effects because increase symptoms of Alzheimer’s
memantine (Namenda)
Treatment of Alzheimer’s
Glutamate antagonist
Adjunct or alternative to cholinesterase inhibitors in AD
NMDA receptor inhibitor
levadopa (L-DOPA, Dopar)
Treatment of Parkinson’s disease
Immediate metabolic precursor of dopamine (crosses BBB)
MOA: transported into CNS–>converted to DA–>stimulates D2 and D1 receptors
Pharmacological effects: ameliorates symptoms of Parkinson’s disease
Not always used 1st due to development of disabling response fluctuation over time (3-4 yrs diminishes)
Side effects: dyskinesia of face and distal extremeties
Fluctuations in clinical response: wearing off and akinesia returns
GI upsets, postural hypotension, tachycardia, delusions, nightmares
Often pts do not respond well (1/3 can’t tolerate)
Drug holiday: discontinuance of drug for 3-21 days to improve responsiveness and alleviate side effects
Drug interactions: vitamin B6 enhances metabolism of drug–>lowers effect; COMT or MAO-B inhibitors prolongs duration of effect
Avoid use in psychotic pts–>enhances mental illness
Levodopa+carbidopa= typical treatment
Carbidopa inhibits dopa decarboxylase but does not cross BBB–>prevents peripheral degradation of levodopa
pramipexole (Mirapex)
DA receptor agonist
MOA: direct agonist of D3 receptors
Pharmacological effects: reduce symptoms of Parkinson’s, smooth out fluctuation in levadopa
Use: Parkinson’s disease–initial therapy, monotherapy (mild PD), or allows for reduction in levadopa dose
Side effects: GI disturbances, postural hypotension, dyskinesias, sleepiness, headaches, mental disturbances (worse than levadopa), problems with impulse control (gambling, sex, shopping)
NOT used in pts with history of psychotic illness
ropinirole (Requip)
DA receptor agonist
MOA: pure D2 agonist
Use: Parkinson’s disease–monotherapy (mild PD), smooth response fluctuation to levadopa
apomorphine (Apokyn)
DA receptor agonist
Use: subcutaneous route for temporary relief in levadopa-induced dyskinesia
Side effects: nausea and vomiting common, dyskinesias, drowsiness, chest pain, hypotnesion
rasagiline (Azilect)
MAO-B inhibitor-irreversible (non-selective at higher doses)
MOA: inhibits MAO-B at low dose–>decrease DA breakdown
inhibits MAO-A at high dose–>decrease NE degradation
Pharmacological effects: increase DA, neuroprotective effects, enhances and prolongs antiparkinsonism effect of levodopa
Use: adjuntive to levadopa, smooths on-off or wearing-off response to levodopa, early symptomatic treatment
Side effeects: serotonin syndrome with meperidine, SSRIs, and TCAs
selegiline (Deprenyl)
MAO-B inhibitor-irreversible (non-selective at higher doses)
MOA: inhibits MAO-B at low dose–>decrease DA breakdown
inhibits MAO-A at high dose–>decrease NE degradation
Use: adjunctive with levodopa, less potent than rasagline)
entacapone (Comtan)
Catechol-O-Methyltransferase (COMT) inhibitor
MOA: inhibit COMT in periphery–>prolong action of levadopa
Pharmacological effects: prolongs levadopa action, does not enter CNS
Side effects: increased levodopa toxicity, nausea, dyskinesias, confusion
tolcapone (Tasmar)
Catechol-O-Methyltransferase (COMT) inhibitor
MOA: inhibit COMT in periphery–>prolong action of levadopa
Enters CNS, more potent and longer duration of action
Side effects: acute hepatic failure–>requires monitoring of liver functions every 2 weeks
amantadine (symmetrel)
Dopamine release
MOA: unclear but typically an antiviral agent
Less efficacious than levadopa
Side effects: restlessness, depression, irritability, insomnia, agitation, hallucinations, confusion
Overdose–>acute toxic psychosis
Livedo reticularis in pts taking amantadine
benztropine (Cogentine)
Anticholinergic agent
MOA: antagonist at M receptors in basal ganglia
Use: PD
Pharmacological effects: reduces tremor and rigidity
Side effects: sedation, mydriasis, urinary retention, constipation, confusion, dry mouth
trihexyphenidyl (Artane)
Anticholinergic agent
MOA: antagonist at M receptors in basal ganglia
Use: PD
Pharmacological effects: reduces tremor and rigidity
Side effects: sedation, mydriasis, urinary retention, constipation, confusion, dry mouth
