NMS and EPS Flashcards
EPS definition and association
constellation of disorders relating to movement
associated with exposure to dopamine antagonists
EPS acute manifestation
dystonia
akathisia
parkinsonism
EPS chronic manifestation
Tardive Dyskinesia
Acute EPS pathophysiology
Release of ACH is regulated by release of dopamine
Dopamine inhibits ACH
But when taking D2, the D2 receptors blocked and the ability to inhibit ACH blocked
So more ACH released which leads to the movement sx
Dystonia definition, onset, course, sx
Prolonged and unintentional contractions of voluntary and or involuntary muscles
Can occur within hours of 1st dose of antipsych drug
Occasionally chronic presentation
Causes repetitive and twisting movements
Often affects the head and neck
Visuals
Dystonia presentations and name
oculogyric crisis
trismus
torticollis
blepharospasm
Dystonia tx prophylaxis
anticholinergic (benztropine) in higher risk pt
also if admin 1st dose high potency IM
Dystonia tx acute/urgent
options:
Biperiden 5mg
benztropine 1-2mg
diphenhydramine 50mg IM or IV
also consider BZD in oculogyric crisis that doesnt respond to anticholinergic rx
Akathisia definition, onset, risk factor
subjective and objective psychomotor restlessness
Patients often unable to remain still: “mounting tension” or irresistible urge to move around
Typically occurs early in treatment with antipsychotics
Risk appears to be higher in antipsychotic-naïve patients started on a new drug
Akathisia tx
reduce dose or d/c
1st line tx propranolol 10mg and titrate to response
2nd line: 5HT2A antagonist (mirtazapine, cyproheptadine) and BZD
Akathisia prevention
avoid polypharmacy and rapid dose inc with antipsychotics
lower risk drug for akathisia
risperidone
olanzapein
ziprasidone
quetiapine
parkinsonism sx, patient profile
Drug-induced Parkinsonism is associated with bradykinesia, postural instability, tremor, and rigidity
More common in elderly and female patients
parkinsonism differentiation
Differentiating between idiopathic and drug-induced Parkinsonism:
Drug-induced presents as symmetrical akinetic rigidity
Follows the ingestion of an associated medication
Does not respond to anti-Parkinson’s drugs
Parkinsonism tx
reduce dose
switch to agent with lower risk
Benztropine (caution in elderly)
Amantadine (useful in elderly r/t anticholinergic)
Tardive Dyskinesia onset, sx, presentation, risk factor, prognosis
Onset: months to years and slow
Presents as involuntary movements of lower face, limbs, trunk
Ex: lip smacking/puckering, tongue movements, excessive blinking
May also present with sx similar to EPS, tremor, myoclonus, tourettism
Risk factor: early presence of EPS
Prognosis: may be irreversible
Tardive Dyskinesia pathophysiology
chronic blockade of D2 receptors leads them to up regulate
upregulation takes time hence why slow onset
now patient is hypersensitive to dopamine which causes involuntary movements
Tardive Dyskinesia tx
reduce or switch: Little benefit
VMAT2 inhibitor: Valbenazine, deutetrabenazine
modest evidence for clonazepam
Gingko biloba extract
AIMS scale
Applies to any EPS acute or chronic
Diagnosing EPS
Includes dental status cuz it looks like EPS
Important if they are going to be on antipsychotic therapy
antipsychotic AE profile chart
Neuroleptic Malignant Syndrome and sx
Acute side effect of neuroleptic medications
Characterized by:
fever
muscular rigidity
altered level of consciousness
autonomic instability
DSM criteria for NMS
hyperthermia >38 on 2 separate occasions
CPK >4x ULN
mental status change: delirium, ALOC
Autonomic activation:
tachy >25% inc
diaphoresis
BP inc >25%
BP fluctuation >20 dia or >25 syst
incontinence
pallor
tachypnea >50% inc
NMS DDX and key difference
NMS etiology
not well understood
Thinking is that a dopamine antagonist can lead to a hypothalamic dopamine blockade
this Can cause hyperthermia and autonomic dysfunction
That leads to cascade of other sx
1. Vasomotor sx
2. Issues with sympathetic nervous system
3. ALOC
Not many build on to each other
1. Hyperthermia leads to inc sweating which leads to dehydration which can lead to kidney complications
Supported by inc rate of NMS in those initiating antipsychotics
NMS risk factors modifiable
- High Temperature
- Low Iron
- Dehydration
- Restraint
- Medication with D2 antagonistic activity
(IV or IM administration associated with greater risk)
NMS risk factors not modifiable
- Advanced Age
- Personal or Family History of Catatonia
- Concurrent Medical Conditions
NMS risk factor drugs: antipsychotics
Antipsychotic Drugs
Atypical:
* Clozapine, olanzapine, risperidone, quetiapine, aripiprazole, paliperidone, asenapine, ziprasidone
Typical:
* Haloperidol, fluphenazine, thioridazine, chlorpromazine, prochlorperazine, loxapine, periciazine, trifluoperazine, flupentixol, zuclopentixol, methotrimeprazine
SGAs are more associated with EPS and NMS but SGAs implicated too
Clozapine: may present differently (less
rigidity/tremors)
NMS risk factor drugs: others
Other Drugs
Mood Stabilizers
* Lithium, carbamazepine
Antidepressants
* Paroxetine, sertraline, amitriptyline
Antiemetics
* Metoclopramide
Evidence for the role of these drugs in NMS is limited
management of NMS: first
1st: D/c suspected agent
dont wait for lab results
NMS staging based treatment
Basically it is 1-5
1 looks like typical EPS and you may be able to get away with switching the agent
3 looks like proper NMS and will need to d/c the agent
NMS mgmt supportive care
note there is an aspiration risk
note that an antipyretic may not work
NMS mgmt pharmacotherapy: supportive
Agitation
* Benzodiazepines can be used to control agitation
Blood Pressure Control
* NMS is associated with severe and labile HTN
* Beta blockers such as labetalol and DHP calcium channel blockers such as amlodipine have been used
VTE
* Use heparin as necessary for VTE prophylaxis
NMS mgmt pharmacotherapy: treatment
Three main agents:
1. Dantrolene
2. Bromocriptine
3. Amantadine
limited data
Dantrolene
Mechanism: peripheral skeletal muscle relaxant
* Directly decreases rigidity and hyperthermia
- Most useful in cases with severe hyperthermia and rigidity
Dosing
* 1-2.5mg/kg IV initially, followed by 1mg/kg every six hours
Adverse effects
* Anaphylaxis, hepatotoxicity, flushing, heart failure, tachycardia
Bromocriptine
Mechanism: Dopamine agonist
* Displaces dopamine antagonist drugs from D2 receptors
Dosing
* 2.5mg every 8-12 hours via NG tube
Adverse effects
* Hypotension, GI ulcer, psychosis
Amantadine
Mechanism: Dopamine agonist
* Displaces dopamine antagonist drugs from D2 receptors
Dosing
* 200-400mg daily in 2-3 divided doses
Adverse effects
* Orthostatic hypotension, agitation, UTI, nausea
Reinitiating antipsychotics after NMS
note future risk of NMS episodes
–30% possibly
wait 2 wks before resuming rx
start low with rx that is low potency and titrate slowlyt
thermoregulation in schizophrenia
Dysregulation is common
Different baseline
Abn daily range
Impaired compensation to heat but more effective compensation to cold
May be cuz of dx or rx but don’t know
Good to counsel patients
1. May have poor access to air conditioning
