Exam 3 Neuro Part 2 & 3 Drugs Flashcards
what are the three ways PD can be treated
- dopamine replacement therapy
- dopamine agonist therapy
- anticholinergic therapy
what are the different types of dopamine replacement therapy to treat PD
- levodopa-carbidopa (Sinemet)
- MAO-B Inhibitors
- COMT inhibitor
- Amantadine
what are the different types of dopamine agonists to treat PD
- Amantadine
2. dopamine agonists
what are the long term effects of dopamine replacement
MOVEMENT RELATED COMPLICATIONS
- dyskinesia
- motor fluctuations (wearing off phenomenon, on-off medication state)
as many as 84% have reported issues
what is the first like option of treatment for PD
levodopa-caribidopa (sine met)
and
dopamine agonists
what is the MOA of levodopa-caribidopa
levodopa: precursor to dopamine that can cross BBB and has CNS action
carbidopa: stops breakdown of 1-dopa to dopamine in periphery so more 1-dopa crosses BBB
levodopa-caribidopa AE
- motor disturbances
- end dose “wearing off” so stiffness and rigidity return
- med not having an effect due to absorption issues
- freezing
- “on” period dyskinesia (must differentiate from PD tremors)
MAO-B inhibitors MOA
inhibits monoamine oxidase B which typically breaks dopamine thus increasing dopamine levels in CNS
Indication of MAO-B
usually used after levodopa-carbidopa and dopamine agonists for PD
both approved adjunct therapy to reduce end dose wearing off with 1-dopa
types of MAO-B inhibitors
selegiline PO and Rasagiline
COMT inhibitor MOA
inhibits COMT which intern decreases breakdown of 1-dopa
MAO-B inhibitors AE
Seleginine PO: has first pass metabolism and increases hallucinations, insomnia, jitteriness
Rasagiline: approved mono therapy but is less effective
COMT inhibitor AE
involuntary movements, nausea
COMT inhibitor indication
used as adjunct therapy to reduce end of dose wearing off with 1-dopa
but overall less commonly used
Amantadine MOA
unknown
possibly increases dopamine release or may have direct affect on dopamine neurons
Amantadine AE
confusion hallucinations diziiness dry mouth constipation lived reticularis
Amantadine indication
was previously used for flyu
usually in early disease management, younger people usually respond better
modest mono therapy benefit and adjust therapy to reduce dyskinesias with 1-dopa
dopamine agonists MOA
binds to and agonizes dopamine receptors
dopamine agonists drug
ropinirole (Requip)
dopamine agonists AE
nausea, drowsiness, dizziness, syncope
monitor for lightheadedness and postural hypotension, hallucinations, lower-extremity edema
less common: impulsive behavior, sleep attacks
dopamine agonist indication
first line treatment
used as mono therapy esp in younger pts and adjunct therapy to reduce end of dose wearing off with 1-dopa
anticholingeric therapy for PD MOA
antagonizes muscarinic receptors to prevent acetylcholine binding
anticholingeric therapy for PD AE
anticholinergic effects
anticholingeric therapy for PD indication
used as mono therapy or adjunct treatment specifically for tremor
limited use bc of AEs and modest benefit
istradefylline (Nourianz) indication
new drug for PD
istradefylline (Nourianz) class
A2A receptor antagonist
istradefylline (Nourianz) MOA
blocks adenosine A2A receptor in the basal ganglia (region which controls movement)
exact MOA is unknown
istradefylline (Nourianz) indication
used as add therapy to levodopa/carbidopa to treat “off” episodes
istradefylline (Nourianz) AE
worsening dyskinesia
what are the 2 aspects to MS treatment
- disease modifying therapies
2. symptom management
interferon B (IFN-B) indication
used submit or IM to treat relapsing MS to decrease exacerbations and delay accumulation of physical disability
interferon B (IFN-B) class
interferon
interferon B (IFN-B) MOA
unknown
but typically is a protein produced by fibroblasts and has an impact on immune function
interferon B (IFN-B) AE
- flu like sx and injection site reaction
- fatigue, depression, pain, abdominal pain, nausea, leukopenia, increase LFTs, myalgia, back pain, weakness, fever
monitor for neuropsychiatric changes, drug induced hypothyroidism, worsening cardiac function
glatiramer acetate (Copaxone, Glatopa) class
miscellaneous biologic agent
glatiramer acetate (Copaxone, Glatopa) MOA
reduce autoimmune response to myelin by reducing T-cell response against myelin
glatiramer acetate (Copaxone, Glatopa) indiccation
subcut or IM in relapsing MS to decrease exacerbations and lesions on MRI
may NOT slow progession
glatiramer acetate (Copaxone, Glatopa) AE
most common: injection site reaction
other: rash, vasodilation, dyspnea, chest pain (typically resolves within a few mins)
S1P Receptor Modulator drugs
fingolimod (Gilenya)
S1P Receptor Modulator MOA
converted to active metabolite which blocks release of lymphocytes into CNS to decrease inflammation
S1P Receptor Modulator indication
PO daily to decrease exacerbations and overall disease severity
S1P Receptor Modulator AE
headache, increased LFTs
rare AE: macular edema (vision changes), infection
monitor for bradycardia (esp within first 24 hours of first dose)
dimethyl fumarate (Tecfidera) Class
fumaric acid derivative
dimethyl fumarate (Tecfidera) MOA
unknown in MA may have anti-inflammatory properties
dimethyl fumarate (Tecfidera) indication
PO BID to decrease exacerbations and overall disease severity
dimethyl fumarate (Tecfidera) AE
GI (n,v,d, abdominal pain and flushing)
rare: hepatoxicity
monoclonal antibodies drugs
natalizumab (Tysabri)
ocrelizumab (Ocrevus)
monoclonal antibodies MOA
natalizumab MOA: antibody that binds to lymphocytes, preventing them from crossing BBB, decreases inflammation in CNS
ocrelizumab MOA: bind CD20 on mature B cells which impacts antigen presentation and autoantibody formation
monoclonal antibodies indication
used to decrease exacerbations, decrease lesions on MRI and or slow disease progression
monoclonal antibodies AE
infusion release reactions, headache, fatigue, arthralgia
monitor for infection
general treatment of AD
mild approach
cholinesterase inhibitor
general treatment of AD
moderate approach
cholinesterase inhibitor + memantine (more likely to delay progression)
general treatment of AD severe approach
consider if med will provide a benefit, possibly do a med-free trial
Colinesterase inhibitors for AD drugs
donepezil (Aricept)
Colinesterase inhibitors for AD MOA
inhibits acetylcholinesterase to increase ACh to help correct the deficiency
Colinesterase inhibitors for AD duration of benefit
3-24 months
Colinesterase inhibitors for AD AE
primarily cholinergic AE
most common: nausea, vomiting
others: SLUDGE, DUMBELLS, decrease appetite or weight, dizziness, tremor
Beer’s list: avoid if hx of syncope that may be related to bradycardia
NMDA antagonist drugs
memantine (Namenda)
NMDA antagonist MOA
antagonizes NMDA receptor to decreases excitation and neuronal death
NMDA antagonist indication
used with cholinesterase inhibitor or as mono therapy
may be used off-label bc not FDA approved
NMDA antagonist AE
usually well tolerated
monitor for falls and dizziness
a2 agonist for spasticity drugs
tizanidine (Zanaflex)
a2 agonist for spasticity MOA
selectively binds a2 receptors in CNS to decrease excitability of postsynaptic neurons
a2 agonist for spasticity AE
drowsiness, dizziness, asthenia
sedation within 30 mins of dose
hypotension
a2 agonist for spasticity dosing
PO 2-3x a day, start at bedtime and titrate slowly
may take with o with our food but must be consistent
central acting antispasmodics drugs
cyclobenzaprine (Flexeril)
central acting antispasmodics MOA
unknown
may inhibit polysynaptic reflex in spinal cord
also possible GABA and serotonin effects
central acting antispasmodics indication
vary from short term use to longer use of maintenance doses
central acting antispasmodics AE
long term or excessive use may contribute to tolerance and physical dependence
sedation, dizziness
Beer’s list: sedation, fractures, some anticholinergic effects, limited efficacy
Botulinum toxin indication
spasticity
Botulinum toxin MOA
blocks release of ACh into NM junction
Botulinum toxin drugs
botox
Botulinum toxin AE
can develop antibodies after long term use
boxed warning: rare cases of spread to distal tissues
muscle weakness, diplopia, blurred vision, urinary incontinence, swallowing and breathing difficulties
risk is likely highest in kids treated for spasticity
direct acting agents for spasticity (Baclofen) MOA
inhibitory effect on alpha motor neuron through inhibition of excitatory neurons
direct acting agents for spasticity (Baclofen) boxed warning
abruptly stopping medication can lead to…
high fever, AMS, exaggerated spasticity and muscle rigidity, rare cases of rhabdo and organ system failure
direct acting agents for spasticity (Baclofen) indication
useful for spasticity caused by diseases like MA and conditions such as SCI
direct acting agents for spasticity (Baclofen) AE
CNS depressant, muscle weakness, in older adults and TBI - impaired memory and cognition
Baclofen: ITB
intrathecal baclogen
- pump implanted into abdominal area
- fewer systemic side effects
Baclofen: ITB indication
good for long term use
used to treat severe spasticity unresponsive to oral medication
