Remaining Movement Disorders Flashcards
What are some movement disorders?
essential tremors, huntington disease, tourette syndrome, RLS, wilson disease, amyotrophic lateral sclerosis (ALS), myasthenia gravis
What are the first line agents for essential tremor with persistent disability due to tremor?
propranolol
primidone
propranolol + primidone
What can you add to first line agents (Propranolol or Primidone) in essential tremor pts with persistent disability due to tremor?
Gabapentin
Topiramate
Nimodipine
if that still doesn’t work:
limb tremor- DBS
head/voice tremor- botox injections
What is an essential tremor?
A rhythmic and oscillatory movement of a body part
relatively constant freq., varying amp.
Caused by either alternating or synchronous contractions of antagonistic muscles
What is the most common movement disorder?
essential tremor
Propranolol MOA?
non selective BB
-depression of CNS
Dosage of propranolol?
Long acting form preferred
ADEs of propranolol?
lightheadedness, fatigue, impotence, and bradycardia
Contraindication for propranolol?
heart block, asthma, or type 1 diabetes mellitus
What BBs can you give to asthmatics with essential tremor?
Atenolol or Metoprolol
non-selective
Which BBs causes less depression?
Sotalol, Nadolol
What does off label drug use mean?
not approved by food and drug administration but has been showed to be effective and have become typical standard of care
-be careful with this
off label use for Primidone?
anticonvulsant
also used for anesthesia
Dosage of primidone?
start low, gradually increase
ADEs of Primidone?
Sedation!
drowsiness, confusion, fatigue, depression, N/V, ataxia, dizziness, unsteadiness
What is another second line option for tremor with inadequate response to propranolol?
alcohol
What can you use for tremor if Primidone isn;t effective? assumed MOA?
Topiramate
enhances GABA activity
Blocks voltage gated Na channel
Antagonizes AMPA/kainite glutamate receptors (excitatory)
ADEs of topiramate?
nausea, paresthesia, concentration difficulty*
Gabapentin MOA?
NOT GABA agonist
possibly: interacts w/ an auxiliary subunit of voltage sensitive ca2 channels
ADEs of gabapentin
sleepiness, dizziness, gait unsteadiness*, brain fog
How are botox injections used for tremor?
Modest benefit for limb tremor associated with ET
may also help head tremor/voice tremor
MOA of botox injections?
prevents Ca dependent release of acetylcholine and produces a state of denervation
ADEs of botox injection to tx voice tremor?
breathliness, hoarseness, swallowing difficulty
MOA of Alprazolam* or Clonazepam? (Benzodiazepines)
enhance GABA activity
limb tremor if it is aggravated by anxiety
ADEs of Alprazolam?
mild sedation, fatigue
What are some options if you are concerned for Benzo dependance?
Alcohol
Nimodipine (CCB)
What is huntington disease?
Inherited progressive neurodegenerative disorder involving the basal ganglia
- movement abn. +/- cognitive and psychiatric func. abn.
- slow course of progression
How is huntington’s inherited?
autosomal dominant- chromosome 4
What is chorea?
Assoc. with huntington’s
rapid, involuntary, non-repeative movement involving the face, trunk and limbs
Pathophys in Huntington’s ?
GABAnergic neuron is lost; acetylcholine or overactivity of dopaminergic neurons
Tx for huntington’s?
Supportive care!
Chorea- Tetrabenzaine and Deubetrabenazine
Suppressing movement- antipsychotics (dopamine antagonists)
+/- antidepressants, anticonvulsants, Amatadine
Why do we need to be careful with use of antipsychotics in huntington’s pts?
Dopamine antagonist, so need to make sure we’re not causing parkinson’s
Tetrabenazine MOA?
Tetrabenazine: deplete amines, especially dopamine, from nerve endings; acts by inhibiting presynaptic vesicular monoamine transporter type 2
Clinical application of Tetrabenazeine?
reduce sxs severity i.e. chorea
ADEs of Tetrabenazine?
Depression*, hypotension, sedation
Haloperidol MOA?
Blockade of D2 receptors»_space; 5-HT2A receptors
Haloperidol effects?
Some α blockade, but minimal M-receptor blockade, less sedation than phenothiazines
Haloperidol is a…
Butyrophenone
Haloperidol clinical application?
Huntington’s chorea*
Tourette’s syndrome*
Schizophrenia
Bipolar diseoder
Behavioral disturbances
ADEs of Haloperidol?
extrapyramidal dysfunc.
- big movements and posture
(can resemble parkinson’s)
What are some atypical antipsychotics?
Aripiprazole
Clozapine
Olanzapine
Quetiapine
Risperidone
ZiprasidoneAtypical antipsychotics MOA?
Blockade of 5-HT2A receptors
>
blockade of D2 receptors
What are Atypical antipsychotics used for?
Huntington’s
schizophrenia
bipolar disorder
Tourette’s syndrome *
Agitation in Alzheimer’s, Parkinson’s*
ADEs of aytpical antipsychotics?
Agranulocytosis, DM, hypercholesterolemia, hyperprolactinemia, QT prolongation, weight gain
What is tourette syndrome?
Neurological disorder manifested by motor and phonic tics with onset during childhood
Tics are clinical hallmark
What are tics?
sudden, brief, intermittent movements (motor tics) or utterances (vocal or phonic tics)
Most pts with tourette syndrome also have..
ADHD or OCD
Tx of tourette’s syndrome?
Education and counseling for mild sxs
For more bothersome:
-Neuroleptics pimozide (Orap) or haloperidol
off label:
- Fluphenazine (dopamine antagonist)
- Risperidone
- Tetrabenazine
when can you use botox for TS?
if focal or phonic tics
Clinical application of Haloperidol in TS?
reduce vocal and motor tic freq. and severity
Pimozide MOA?
Dopamine receptor antagonist
Pimozoide clinical application?
Severe motor and phonic tics who failed standard treatment
Pimozoide ADEs?
Sedation, akathisia, akinesia
Ocular-accommodation decreased
What is restless leg syndrome?
overwhelming urge to move the legs, assoc. with unpleasant paresthesias
worse at night and at night and relieved by movement
RLS is commonly assoc. with?
sleep disturbances, caffeine, stress, alcohol, and fatigue
What drugs are assoc. with RLS?
Antidepressants (except bupropion)
Antipsychotics
Dopamine-blocking antiemetics (eg, metoclopramide)
Centrally-acting antihistamines
What is Periodic leg movements of sleep (PLMS)?
jerking movements of the leg during sleep
What is Periodic limb movement disorder (PLMD)
when sleep fragmentation and daytime fatigue coexist with PLMS
Tx for RLS?
iron replacement
-if serum ferritin lower than 75
Ferrous sulfate
What can you give for RLS if iron replacement doesn’t work?
alpha 2 delta ligand (gabapentin, pregablin)
dopamine agonist (pramipexole)
When should you give alpha 2 delta ligand for RLS?
sleep disturbance, insomnia, painful RLS, comorbid pain syndrome, hx of current impulses control disorder, anxiety
When should you give dopamine agonist for RLS?
increased risk for falls, severe sxs of RLS, excess weight, metabolic syndrome, OSA, depression
What can be used for the tx of intermittent RLS?
Dopaminergic agents: Levodopa
-Carbidopa-levodopa
Benzodiazepines
- mild cases of RLS, particularly in younger pts
- Clonazepam, Diazepam
ADEs of benzodiazepines?
nocturnal unsteadiness and drowsiness or cognitive impairment in the morning*
Name 2 dopamine agonists. What are they used for?
Pramipexole, Ropinirole
persistent RLS
ADEs of Dopamine agonists
Common–nausea, lightheadedness, and fatigue*
Less common–nasal stuffiness, constipation, insomnia, and leg edema
Concerning-increased risk of impulse control disorders*
Name 2 Alpha 2 delta calcium channel ligands. What are they used for
gabapentin, Pregabalin
persistent RLS
-also: peripheral neuropathy, chronic pain syndrome, insomnia/sleep disturbances*
When are Alpha 2 delta calcium channel ligands preferred for RLS?
in pts with impulse control disorder
BUT increases risk of suicidal thoughts and behavior
When are opioids use for RLS?
for refractory RLS
codeine, tramadol, methadone, oxycodone
Opioid MOA
interaction btwn. spinal opioid and dopamine receptors
What is augmentation?
increased sxs with increased doses of meds
-main comp of dopaminergic therapy in RLS
What is Wilson’s disease?
Recessively inherited disorder of copper metabolism
impaired biliary copper excretion leads to accumulation of copper in several organs
Sxs of wilson’s disease?
Liver: N/V, fatigue, jaundice
CNS: tremors or uncontrolled movements, muscle stiffness, probs with speech, swallowing or coordination
Tx for Wilson’s disease?
Chelating agents: D- Penicillamine, Trientine
oral zinc
What are chelating agents? MOA?
remove extra copper from the body by releasing it from organs into the bloodstream
D penicillamine MOA?
Contains a free sulfhydryl group that functions as a copper chelating moiety
D penicillamine ADEs?
fever, cutaneous eruptions, lymphadenopathy, neutropenia, thrombocytopenia, proteinuria
Give with Pyridoxine 25mg/day to prevent pyridoxal phosphate deficiency
Trientine MOA ?
Functions principally by removing copper from less strongly bound sites on proteins and membranes, and it increases renal copper excretion
Can chelating agents be used in conjunction with iron replacement?
NO
Trientine ADEs?
hypersensitivity rxn and pancytopenia-rare
neuro sxs
What should you monitor in a pt taking Trientine?
24 hours copper excretion- to check for effectiveness
MOA of oral zinc?
interferes with the absorption of copper
Oral zinc ADEs?
GI upset
elevation in serum amylase and lipase without evidence of pancreatitis
What is amyotrophic lateral sclerosis (ALS)
aka Lou Gehrig’s disease
disorder of the motor neurons of the ventral horn of the spinal cord (lower motor neurons) and the cortical neurons that provide their afferent input (upper motor neurons)
gradual deterioration
Sxs of ALS?
weakness, muscle atrophy, fasciculation, spasicity, dysarthria, dysphagia, res. compromise
SPARES sensory, autonomic and oculomotor func.
Tx of ALS?
Riluzole
Free radial scavanger: Edaravone
Riluzole PK?
absorbed orally, high protein bound
high fat meals decrease absorption
Riluzole ADEs?
HTN, abn pain, neuromuscular and arthralgia, tremor, decrease lung func., elevates LFTs
Endaravone ADEs?
injection site contusion, gait disturbance, HA
sodium bisulfite- pos. allergic rxn
What can you use for sxs relief of ALS: spasticity?
Baclofen
Tizanidine
Clonazepam
Baclofen MOA?
GABA B receptor agonist
Baclofen ADEs?
sedation
Tizanidine MOA?
agonists of alpha adrenergic receptors in the CNS
Tizanidine ADEs?
Drowsiness, asthenia, dizziness
Benzodiazepines MOA?
enhances the inhibitor effect of GABA A receptors
ADEs of benzodiazepines?
amnesia, confusion, drowsiness, slurred speech
What is myasthenia gravis?
Neuromuscular disease characterized by weakness and marked fatiguability of skeletal muscle
defect in the synaptic transmission at the neuromuscular junction
Tx of MG?
standard anticholinesterase drugs:
- Pyridostigmine
- Neostigmine
MOA of standard anticholinesterase drugs?
inhibit the action of the metabolizing enzyme acetylcholinesterase
