The following are early onset EPS symptoms
Dystonia
Akathisia
Parkinsonism
Tardive dyskensia
Which EPS symtom can appear within days
Akatsia
Tardive dyskinesia
Which EPS symptom can appear within weeks?
Parkinsonsism
Tardive dyskenia
Which EPS symptom can appear within months?
Which EPS symtoms can take years to appear?
Types of drug-induced movement disorders: Acute: Withdrawal:( Acute:, Withdrawal: ) Occur within a short duration of treatment onset or dose increase Chronic: Tardive( Chronic:, Tardive ) Symptoms persist throughout treatment Tardive Withdrawal( Tardive, Withdrawal ): Delayed onset of symptoms Withdrawal: Tardive( Withdrawal:, Tardive ) Occur in the absence of treatment. May resolve
Dopamine system pathways include: Mesolimbic: arousal, memory, behavior Mesocortical: cognition, socializaiont Tuberoinfundibular: regulation of prolactin Nigrostriatal: modulation of EPS
The mechanism for dystonia is
Dopamine deficiency in the basal ganglia and striatum
Overactive cholinergic system
Dopaminergic/serotonergic or dopaminergic/cholinergic imbalance in the nucleus accumbens
Blockade of the striatal dopamine receptors
What are risk factors for dystonia
Young age
H/O ECT
Male gender
High potency neuroleptics - Haldol, Prolixin
Comorbid medical conditions
Types of dystonia
The MOA for akathisia, from the Greek meaning "inability to sit", is:
Dopaminergic/serotonergic or dopaminergic/cholinergic imbalance in the nucleus accumbens, Overstimulation of locus coeruleus.
Striatal dopaminergic hypersensitivity
Which of the following agents cause akathisia
SSRI
Second generation antipsychotics
Antiemetics
CCB
Anti-anxiolytics
What are some differentials for akathisia
GAD
ADHD
Agitation
MDD
What are clinical presentation of akathisia
Restlessness
Breaking out into song & dance for no reason
Fidgety movements/leg swinging
Marching in place
Rocking from one foot to another
Picking
The risk factors for akathisia include
Advanced age
Affective disorder
Cognitive impairment
Female impersonator performer
Female
H/O akathisia
Iron deficiency
High dose/potency/neuroleptics
Pathophysiology of pseudoparkinsonism is:
Blockade of the striatal dopamine receptors and depletion of pre-synaptic celft
Striatal dopaminergic hypersensitivity and cholinergic deficiency in the basal ganglia
Parkinsonism = bradykesia apraxic slowness( bradykesia, apraxic slowness ) Pseudoparkinsonism = bradykinesia apraxic slowness( bradykinesia, apraxic slowness )
Parkinsonism = resting tremor essential tremor, myoclonus( resting tremor, essential tremor, myoclonus ) Pseudoparkinsonism = resting tremor essential tremor, myoclonus( resting tremor, essential tremor, myoclonus )
Parkinsonism = lead pipe rigidity paratonic rigidity( lead pipe rigidity, paratonic rigidity ) Pseudoparkinsonism = lead pipe rigidity paratonic rigidity( lead pipe rigidity, paratonic rigidity )
Parkinsonism = postural instability frontal ataxia( postural instability, frontal ataxia ) Pseudoparkinsonism = postural instability frontal ataxia( postural instability, frontal ataxia )
Parkinsonism = Slow, shuffling gait with festination Slow, shuffling apraxic gait( Slow, shuffling gait with festination, Slow, shuffling apraxic gait ) Pseudoparkinsonism = Slow, shuffling gait with festination Slow, shuffling apraxic gait( Slow, shuffling gait with festination, Slow, shuffling apraxic gait )
What are risk factors for pseudoparkinsonism?
Male
Central DA receptor binding agents, Metclopramide, phenothiazines
AIDS
Cancer
If identified early can be reversed
is not reversible
increased risk with increased use
increased use does not cause increases risk
early onset
late onset
MOA for tardive dyskinesia
Cholinergic deficiency within basal ganglia
Oxidative stress and cell injur
Genetic susceptibility
Glutamate-induced excitotoxicity
GABA mediated neuronal dysfunction
Which medications most commonly cause tardive dyskinesia?
Meoclopramide
Alpha adrenergic agonists
SGA
FGA
Clinical presention of tardive dyskinesia
Choreiform - characterized by jerky, involuntary movements, chiefly of the face and extremities
Athetoid - characterized by slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet and in some cases, arms, legs, neck and tongue
Stereotypic - petitive, nonfunctional motor behavior (e.g., hand waving or head banging), that markedly interferes with normal activities or results in bodily injury.
EPS can be caused by antiemetics, antieliptics, psychotropics, cardiovascular agents and Levodopa
The following drugs cause all four movement disorders: dystonia, akathisia, Parkinsonism, tardive dyskinesia
Metoclopramide
Prochloraperazine
Amoxapine
Neuroleptics
Levodopa
How often should the Abnormal Involuntary Movement Scale (AIMS) be administered?
Baseline then every week x4 then every 3 months
Baseline then every week x2 then every 12 months
Baseline then every week x2 then every 6 months
What are overall tips for treatment of EPS?
Stop offending agen (if possible)
Reduce the dose
Switch to a second generation antipsychotic
Treat prophylactically
A wing and prayer and refer to anyone else
Dystonia put in order of line of treatment First line = ❌ Second line = ❌ Third line = ❌ Fourth line - ❌
This is a nice visual/review
Drug of choice for dystonia is
Beta-blockers, anticholinergics, benzodiazepines, 5-HT2A receptor antagonist, mirtazapine
Anticholinergics (benztropine, diphenhydramine, trihexyphenidyl)
Clonzaepam, ginkgo biloba
Drugs of choice for akathisia include
Beta-blockers, benzodiazepines, 5-HT2A receptor antagonist, mirtazapine
Clonazepam, ginkgo biloba
Mirtazapine (Remeron)
Used in low doses to treat akathisa
Used in low doses to treat dystonia
Alpha-adrenergic receptor antagonist
Alpha-adrenergic receptor agonist
Antagonizes 5-HT2 and 3 receptors
Visual for treatment of akathisia
Which drugs are used to treat pseudoparkinsonism?
Cogentin (benztropine)
Symmetrel (amantadine)
Benzodiazepines
Diphenhydramine (Benadryl)
MOA for amantadine (Symmetrel) is
Dopamine agonist
Dopamine antagonist
5-HT2 agonist
5-HT2 antagonist
Side effects for benztropine (Cogentin) include
Dry mouth
Hypotension
Diarrhea
Constipation
Sialorrhea
Side effects for amantadine (Symmetrel) include:
Hypertension
Sedation
Worsening s/s of psychosis
Which drugs are used in the treatment of tardive dyskinesia
Diltiazem
Baclofen
Galantamine
Clonazepam
Ginkgo biloba
What is the first FDA approved medication for Tardive Dyskinesia
Velbeazine (Ingrezza)
Benztropine (Cogentin)
Trihexphenidyl (Artane)
Amantadine (Symmetrel)
What is the MOA for valbenazine (Ingrezza)?
Blocks alpha-adrenergic receptors and antagonizes 5-HT2 and 3 receptors
Reversible inhibition of vesicular monoamine transporter 2 (VMAT2), a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release
Increase in synthesis and release of dopamine, and inhibition of dopamine uptake.
Selective M1 muscarinic acetylcholine receptor antagonist. It is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular)
Acute dystonia is considered a medical emergency. Must seek treatment immediately. May require IV diphenhydramine
Velbenazine is extensively metabolized by hydrolysis to form active metabolite and by oxidative metabolism to form mono-oxidized valbenazine and other minor metabolites
High fat meals may decrease increase( decrease, increase ) absorption of valbenazine (Ingrezza)
Common adverse side effects of valbenazine (Ingrezza) include:
Fatigue
HA
UTI
Somnolence
Warnings for valbenazine (Ingrezza) include:
QTc prolongation
Pregnancy/breastfeeding
Valbenazine should not be used in:
Severe renal impairment (< 30 mL/min)
CHF
Cirrhosis
Pancreatitis
Strong 3A4/2D6 inhibitors: Increase Decrease( Increase, Decrease ) valbenazine concentration Strong 3A4 inducer: Increase Decrease( Increase, Decrease ) valbenazine concentration
Valbenazine (Ingrezza) interacts with MAOIs by increasing decreasing( increasing, decreasing ) the monamine NT in the synapse
Valbenazine (Ingrezza) interacts with digoxin and increase decreases( increase, decreases )s the digoxin concentration by p-glycoprotein inhibtion inducer( inhibtion, inducer )
Deutetrabenazine (Austedo) is used for the treatment of chorea and schizophrenia/schizoaffective disorder. It is metabolized by CYP2D6