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L1: CNS Diseases- parkinsons and alzheimers

Terms in this set (62)

Levodopa: MOA?
transported to CNS and converted to dopamine (DA)
Carbidopa: MOA?
inhibits peripheral breakdown of levodopa

L-aromatic acid decarboxylase (DOPA decarboxylase) inhibitor
Levodopa: Rx?
parkinson's
off label for restless leg syndrome
Carbidopa: Rx?
parkinson's
off label for restless leg syndrome
Levodopa is a _________________ to dopamine that is converted peripherally and centrally.
precursor
Why should levodopa never be used as a mono therapy?
only 1-3% of it gets to the brain
Levodopa is metabolized peripherally by __________ and ____________ and centrally by _________.
DOPA decarboxylase
COMT

DOPA decarboxylase
Levodopa has a major ________ ___________ effect.
first pass
What are the peripheral side effects of dopamine replacement drugs levodopa and carbidopa?
-N/V (chemoreceptor trigger zone is activated by dopamine)
-Cardiovascular: postural hypotension and dysrthythmias
What are the central side effects of dopamine replacement drugs levodopa and carbidopa?
-N/V (chemoreceptor trigger zone is activated by dopamine)
-dyskinesias*
-psychosis/agitation
-impulse control issues (hyper sexual)
-hallucinations
What is the honeymoon period associated with dopamine drug replacements, levodopa and carbidopa?
when patient's are first diagnosed, they have mild symptoms and the therapy they start on makes their s/sx disappear for a couple of years, and they think they are cured... but they are not
What is the wearing off phenomenon associated with dopamine drug replacements, levodopa and carbidopa?
The point at which normal doses of medications are no longer working and symptoms begin to return (at this point, we increase drug levels)
What is the on/off phenomenon associated with dopamine drug replacements, levodopa and carbidopa?
off phase: symptoms return
on phase: symptoms resolve
Name which drugs are used in the treatment of parkinson and which are used in the treatment of alzheimers:
levodopa
carbidopa
entacapone
donepezil
amantadine
selegiline
ropinirole
memantine
bromocriptine
benztropine
levodopa
carbidopa
entacapone
Alzheimers: donepezil
amantadine
selegiline
ropinirole
Alzheimers: memantine
bromocriptine
benztropine

the rest are parkinson's drugs
What is parkinson and which neurotransmitter is involved... where is the involvement located in the brain?
neurodegenerative disorder

destruction of dopamine neurons in the substantial nigra (basal ganglia)

loss of balance (no dopamine to compete with acetylcholine binding and there is uninhibited ACh action)
What are the s/sx associated with parkinsons? when do s/sx appear?
TRAP
tremor
rigidity
akinesia
postural instability/pill rolling

appear when 60-80% of dopamine neurons are destroyed
Where in the brain does dopamine and ACh compete?
striatum of the basal ganglia
Can you treat parkinson's with exogenous dopamine? why or why not?
NO, it cannot cross the BBB
To get dopamine, _____________ ____________________ (amino acid) must be converted into ______________, which can then be converted into dopamine.
tyrosine hydroxylase

L-aromatic acid decarboxylase (DOPA decarboxylase)
What two enzymes break down dopamine peripherally?
MAO (monoamine oxidase)
COMT (catecholamine methotrexate)
What percentage of dopamine is metabolized in the:
1) gut
2) periphery
3) brain
1) gut 70-90%
2) periphery 10-30%
3) brain 1-3%
Levodopa is broken down peripherally by what two enzymes? what is created?
COMT --> dopamine metabolites

L-aromatic acid decarboxylase (DOPA decarboxylase) --> dopamine
Levodopa is broken down centrally in the brain by what enzyme? what is created?
L-aromatic acid decarboxylase (DOPA decarboxylase)--> dopamine
What determines what type of adverse effects are experienced by patients taking dopamine replacement, levodopa?
if it is broken down peripherally vs centrally
Entacapone: MOA?
prevents breakdown of levodopa into inactive metabolites in the periphery by inhibiting COMT (Catechol-O-methyltransferase); therefore, allowing more levodopa to cross the BBB and turn into dopamine

ONLY WORKS PERIPHERALLY
Entacapone: Adverse effects?
-intensifies effects of levodopa (dyskinesias, hypotension, hallucinations)
-vomiting/diarrhea/ constipation
-Orange/yellow discoloration of urine
-hepatocellular injury and liver failure***
Can entacopone be used by itself?
alone, it has no effect
Selegiline: MOA?
irreversibly inhibits MAO-B, which decreases the breakdown of dopamine centrally
Selegiline: contraindications?
do not give to someone who is on meperidine... could increase risk for serotonin syndrome
Selegiline: Rx?
parkinsons
depression
Selegiline: adverse effects?
-intensify effects of levodopa (dyskinesias, orthostatic hypotension, psychosis, hallucinations)
-insomnia
-hypertensive crisis in high doses due to increased levels of NE (if MAO-B looses selectivity, it starts to inhibit MAO-A... increasing NE levels)
Which drugs to treat parkinson are considered dopamine replacements?
levodopa
carbidopa
Which drugs used to treat parkinson are considered to be direct acting dopamine (D2) agonists?
ropinirole
bromocriptine
Direct acting dopamine (D2) agonists (Do/Do Not) require activity of the degenerating neurons.
DO NOT
What are the advantageous of direct acting dopamine (D2) agonists?
-don't require the activity of degenerating neurons
-more selective and perhaps fewer adverse effects
-no competition with amino acids for transport
-lower incidence of fluctuating response and dyskinesias
What would be a counseling point for the used of direct acting dopamine agonists if used for restless leg syndrome?
-take at night because the medication can cause sedation
Ropinirole: MOA?
directly stimulates dopamine receptors
Bromocriptine: MOA?
directly stimulates dopamine receptors
Ropinirole: Rx?
Parkinsons
Restless leg syndrome
Bromocriptine: Rx?
parkinsons
acromegaly
hyperprolactinemia (excess breast milk)
Ropinirole: adverse effects?
-nausea
-postural/orthostatic hypotension
-confusion
-impulse control issues
-hallucinations
-sedation (sleep attacks)
Bromocriptine: Adverse effects?
-nausea
-postural/orthostatic hypotension
-confusion
-impulse control issues
-hallucinations
-sedation (sleep attacks)
Amantadine: MOA?
-unknown
-anti-viral
-weak NMDA receptor antagonist
-stimulation of dopamine from storage vesicles
-has some anticholinergic properties (perhaps to bring ACh levels down)
Amantadine: Adverse Effects?
-orthostatic hypotension
-livedo reticularis (spider web veins)
Amantadine: Rx?
-parkinsons
-dyskinesias caused by Levodopa (drug induced extrapyramidal reactions)
-influenza A (CDC must give the ok)
Benztropine: MOA?
blocks ACh receptors in the striatum (muscarinic)

antagonist centrally, but can work in periphery
Benztropine: adverse effects?
-anticholinergic effects (Can't see, pee, spit, shit)
-periphery (opposite of SLUDGE)
-centrally (sedation/confusion/hallucination)
Benztropine: Rx?
-parkinsons
-extrapyramidal symptoms (EPS): tremor, rigidity
IF you are diagnosed with parkinson's, what drug are patients typically started on?
levodopa/carbidopa
OR
dopamine agonist 2x/day
What can you do if a parkinson's patient is experiencing a "wearing off" phenomenon?
-change med
-change dosage
-change frequency
-add med
-add amantadine/ anticholinergic if patient begins to experience dyskinesias
What do you do if your parkinson's patient begins to experience a dyskinesia?
add amantadine or an anticholinergic to their treatment
What is alzheimer's disease characterized by?
-cerebral atrophy
-degeneration of cholinergic neurons
-beta amyloid plaques
-neurofibrillary tangles
-tau proteins
-neuronal degeneration early in hippocampus and late in cerebral cortex
What neurotransmitter is involved with alzheimers?
ACh
levels of this NT are 90% below normal
ACh is an important NT in the __________________ and ___________ ____________ for memory.
hippocampus
cerebral cortex
What is a genetic marker for alzhemiers?
apolipoprotein E (apoE4)
What is the most common drug for the treatment of mild to moderate alzheimers?
donepezil
Donepezil: MOA?
blocks acethylcholinesterase (enzyme which normally breaks down acetylcholine) in order to enhance transmission by central cholinergic neurons not yet destroyed
Donepezil: Rx?
-alzheimer's
-off label for dementia associated with parkinson's (lewy body)
Donepezil: Adverse Effects?
-GI upset (cholinergic effects)
-cholinergic effects (SLUDGE and killer Bs)
Memantine: MOA?
N-Methyl-D-Aspartate (NMDA) Receptor Antagonist

this drug inhibits glutamate (inhibiting neuron excitation)

glutamate (primary excitatory amino acid in CNS) may contribute to the pathogenesis of alzheimer's by overstimulating various glutamate (NMDA) receptors, leading to excitotoxicity and neuronal cell death
Memantine: Rx?
-moderate to severe alzheimer's disease
-off label for vascular dementia
Memantine: adverse effects?
-dizziness
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