Remaining Movement Disorders Flashcards
Essential Tremor: first line agent
propanolol
- beta 2 antagonist
- depression of CNS activity
- can cross BBB
- prefer long acting
- ADE: lightheadedness, fatigue, impotence, bradycardia
- caution: heart block, asthma DM1
others:
sotalol
nadolol (less depression)
asthmatic patients:
atenolol
metropolol
Essenetial Tremor: other treatment options
alcohol
- ET related gait ataxia
nimodipine
-limb tremor associated w/ ET
Essential Tremor
rhythmic and oscillatory movement of a body part
- constant frequency
- variable amplitude
caused by alternating or synchronous contractions of antagonistic muscles
MC movement disorder
MC neurologic cause of postural/action tremor
Essential Tremor: Anticonvulsant: Primidone
off label
metabolite: phenobarbital
gradual inc in dose
ADEs:
- SEDATION, drowsiness, confusion, fatigue, malaise
- DEPRESSION
- N/V
- ataxia, dizziness, unsteadiness, vertigo
Essential Tremor: Anticonvulsant: Topiramate
enhances GABA
blocks voltage gated Na channel
antagonizes AMPA/kainite glutamate receptors
ADEs:
- nausea
- paresthesia
- DIFFICULTY CONCENTRATING
causes weight loss
Essential Tremor: Anticonvulsant: Gabapentin
NOT GABA agonist
interacts w/ voltage gated Ca channels
ADEs:
- sleepiness
- dizziness
- GAIT UNSTEADINESS
Essential Tremor: Botulinum Toxin Type A Injections
for limb tremor
associated w/ dose dependent hand weakness
may reduce head, voice tremor
prevents Ca dependent release of acetylcholine –> denervation
-only affects presynaptic membrane
ADEs:
- breathiness
- hoarseness
- swallowing difficulty
Essential Tremor: Benzodiazepines
alprazolam, clonazepam
enhance GABA activity
limb tremor
dependence risk
ADEs:
- mild sedation
- fatigue
Huntington Disease
inherited progressive neurodegenerative disorder involving the basal ganglia
slow course
autosomal dominant - chromosome 4
GABAergic neuron is lost - acetylcholine or overactivity of dopaminergic neurons
Huntington Disease: symptoms
neurologic: chorea, dystonia, eye movement slowing, hyperreflexia, gait abnormality, myoclonus, parkinsonism
psychiatric: apathy, irritability, depression, delusions, aggression, anxiety, disinhibition, paranoia
cognitive: poor judgement, inflexibility of thought, loss of insight, dec concentration, memory loss, subcortical dementia
rigidity
bradykinesia
Huntington Disease: chorea
rapid involuntary nonrepetitive movement
involves face, trunk, limbs
Huntington Disease: treatment
supportive
chorea: tetrabenazine, deutetrabenazine
movement suppression: antipsychotic dopamine antagonist (halperidol, fluphenazine, olanzapine)
antidepressants
anticonvulsants (topiramate, levetiracetam)
amantadine
Huntington Disease: reduction of abnormal movements may be associated with…
iatrogenic parkinsonism
through low brain dopamine levels
Huntington Disease: Tetrabenazine (T), Deutetrabenazine (D)
deplete dopamine
inhibit presynaptic transporter (VMAT2)
reduce sx and severity
T: ADE: depression
D: advantage: prolonged half life (less frequent, lower dosing)
Huntington Disease: butyrophenone: haloperidol
blockade of D2 receptors»_space; 5-HT2A (serotonin) receptors
clinical applications:
schizophrenia, bipolar, HUNTINGTON (chorea, dyskinesia, behavioral disturbances), TOURETTE’S
ADE: extrapyramidal dysfunction
Huntington Disease: Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprasidone
blockade of 5-HT2A (serotonin) receptors > D2 receptors
clinical applications: schizophrenia, bipolar, major depression, agitation in alzheimer’s and parkinson, TOURETTE’S
Tourette Syndrome
neurologic disorder manifested by motor/phonic tics
onset: childhood
disturbance of striatal thalamic cortical (mesolimbic) spinal system –> disinhibition of motor and limbic system
comorbidities: ADHD, OCD
Tourette Syndrome: hallmark
Tics: sudden brief intermittent movements (motor) or utterances (vocal/phonic)
fluctuating severity
unpredictable pattern
Tourette Syndrome: treatment
education + counseling (habit reversal training)
Dopamine Depletion: neuroleptics (pimozide, haloperidol) fluphenazine risperidone, aripirazole, ziprasidone tetrabenazine
Tourette Syndrome: haloperidol
D2 receptor blocker
reduce tic frequency, severity
ADE: extrapyramidal dysfunction
Tourette Syndrome: pimozide
dopamine receptor antagonist
for severe tics that failed standard treatment
ADEs: sedation, akathisia, akinesia, dec ocular accommodation
Tourette Syndrome: medications
Clonidine, guanfacine used w/ comorbid ADHD
Phenothiazines, atypical antipsychotics, clonazepam, carbamazepine: Sometimes of value
Restless Leg Syndrome
aka willis ekbom disease
overwhelming urge to move the legs
- worse at night
- relieved by movement
Restless Leg Syndrome: exacerbated by…
- caffeine
- stress
- fatigue
- antidepressants (not bupropion)
- antipsychotics
- dopamine blocking antiemetics (metoclopramide)
- centrally acting antihistamines
Restless Leg Syndrome: periodic leg movements of sleep (PLMS)
jerking movements of the legs during sleep
Restless Leg Syndrome: periodic limb movement disorder (PLMD)
sleep fragmentation and daytime fatigue with PLMS
Restless Leg Syndrome: treatment: iron replacement
if serum ferritin < 75mcg/L
agent: ferrous sulfate
take with vitamin C - enhances absorption
ADE: constipation, GI upset
Restless Leg Syndrome: alpha 2 delta ligand: clinical factor indications
sleep disturbance disproportionate to other symptoms
comorbid insomnia
painful restless legs
hx/current impulse control disorder
comorbid generalized anxiety disorder
Restless Leg Syndrome: dopamine agonist: clinical factor indications
increased risk for falls
severe symptoms of RLS
excess weight, metabolic syndrome, OSA
comorbid depression
Restless Leg Syndrome: drugs to avoid with a history or current alcohol or substance abuse
hepatically metabolized (eg: ropinirole, rotigotine)
Restless Leg Syndrome: drugs to avoid with pregnancy risk
dopaminergic agents
alpha 2 delta ligands
consider instead the use of iron
Restless Leg Syndrome: drugs to avoid with impaired renal function
pramipexole
avoid/adjust dose in alpha 2 delta ligands
Restless Leg Syndrome: drugs to avoid with hepatic impairment
ropinirole
use caution with rotigotine patch
Intermittent Restless Leg Syndrome: Treatment: Dopaminergic Agents
carbidopa levidopa
useful for specific triggers (lengthy travel, events with prolonged sitting)
avoid exceeding 200mg/day
Intermittent Restless Leg Syndrome: Treatment: Benzodiazepines
clonazepam (long acting), diazepam (erratic)
for younger patients
ADEs:
- nocturnal unsteadiness
- drowsiness
- cognitive impairment in the morning
Persistent Restless Leg Syndrome: Treatment: Dopamine Agonists
pramipexole, ropinirole
onset: ~90-120 minutes
ADEs:
- nausea, lightheadedness, FATIGUE
- NASAL STUFFINESS, constipation, insomnia, LEG EDEMA
- RISK OF IMPULSE CONTROL DISORDERS
Persistent Restless Leg Syndrome: Treatment: Alpha 2 Delta Ca Channel Ligands
gabapentin, pregabalin
indications:
- comorbid painful peripheral neuropathy
- unrelated chronic pain syndrome
- comorbid insomnia/sleep disturbances that is disproportionate
- pts with impulse control disorder
caution:
inc risk of suicidal thoughts/behaviors
ADE: dizziness
Refractory Restless Leg Syndrome: Treatment: Opioids
low potency: codeine, tramadol
high potency: methadone, oxycodone, hydrocodone
MOA: interaction bt spinal opioid and dopamine receptors
ADEs:
tolerance
constipation
Restless Leg Syndrome: Augmentation
main complication of dopaminergic pathway
results in overall inc in symptom severity with increasing doses of medication
Wilson’s Disease
recessive, inherited disorder of copper metabolism
impaired biliary copper exretion –> copper accumulates in organs (liver, brain, cornea)
Wilson’s Disease: symptoms
kayser fleischer rings
N/V, fatigue, muscle cramps, jaundice
tremors, muscle stiffness, problems with speech swallowing and physical coordination
Wilson’s Disease: treatment
chelating agents
oral zinc
Wilson’s Disease: Treatment: Chelating Agents
D penicillamine, trientine
removes excess copper by releasing it from organs into bloodstream
binds copper making it unavailable for activity
ADEs: nervous system symptoms
Wilson’s Disease: D-penicillamine
contains free sulfhydryl group that chelates copper
depletes pyridoxine (B6) - supplement to prevent pyridoxal phosphate deficiency
ADEs: early onset: -fever -cutaneous eruptions -lymphadenopathy -neutropenia -thrombocytopenia -proteinuria
late onset:
-proteinuria
Wilson’s Disease: Treatment: Trientine Copper Chelator
lacks sulfhydryl groups
removes copper and inc renal copper excretion
poorly absorbed
approved for children
also chelates iron
coadministration of iron should be avoided (nephrotoxocity)
may lead iron overload in the liver
ADEs:
rare: hypersensitivity rxn, pancytopenia
neurologic worsening
Wilson’s Disease: Treatment: Oral Zinc
induces metallothionein to bind luminal copper - excreted in stool
Forms:
- zinc acetate (best absorption)
- zinc gluconate (more tolerable)
ADEs:
GI upset
elevation of serum amylase and lipase w/out clinical evidence of pancreatitis
Amyotrophic Lateral Sclerosis (ALS)
gradual degeneration and death of motor neurons (UMN, LMN)
rapidly progressive
spares sensory, autonomic, oculomotor function (usually cognitive function too)
ALS: signs and symptoms
weakness muscle atrophy fasciculations spasticity dysarthria dysphagia respiratory compromise
ALS: etiology
abnormal glutamate uptake –> glutamate accumulation and excitotoxic injury
ALS: Treatment: Riluzole
inhibits glutamate release
inactivates voltage dependent Na channels
interferes with intracellular events
blocked by pertussis toxin (G protein interaction)
highly protein bound (high fat meals dec absorption)
metabolized by liver
ALS: Treatment: Riluzole: ADEs
HTN abdominal pain neuromuscular and arthralgia, tremor dec lung function elevated serum transaminases
ALS: Treatment: Edaravone
free radical scavenger
prevents oxidative damage to cell membranes
slows the decline of physical function
indications:
- ALS for 2yrs or less
- living independently
- FVC 80+%
ALS: Treatment: Edaravone: ADEs
injection site contusion, gait disturbance, headache
contains sodium bisulfite
- allergic reactions
- asthmatic reactions
ALS: Symptomatic Therapy: Spasticity: agents
baclofen
tizanidine
clonazepam
ALS: Baclofen
GABA receptor agonist
acts to restore lost inhibition by stimulating postsynaptic GABA receptors
ADE: sedation
ALS: Tizanidine
alpha 2 adrenergic receptor agonist in the CNS
presynaptically stimulates GABA release from spinal cord inhibitory interneuron
ADEs:
drowsiness
asthenia
dizziness
ALS: Benzodiazepines
diazepam, clonazepam
antispasticity agents
contributes to respiratory depression in late stage
enhances inhibitory effect of GABA receptors
ADEs: amnesia confusion drowsiness slurred speech
Myasthenia Gravis
neuromuscular disease characterized by weakness and marked fatigability of skeletal muscle
defect at the synapse - autoimmune response to ACh receptor at the end plate
Myasthenia Gravis: Treatment: Anticholinesterase
pyridostigmine, neostigmine
inhibits acetylcholinesterase (metabolizing enzyme)
Myasthenia Gravis: Anticholinesterase: ADEs
salivation lacrimation urination defecation GI upset emesis
cardio
respiratory
pupil constriction
