Transcript Psychotropic Drugs

Psychotropic Drugs
Jeff Hurley MD
Martin Luther King Jr. Hospital
Emergency Medicine
Objectives
Review common psychiatric drugs
Side effects and interactions
Signs and symptoms of overdose
Treatment of acute overdose
Antipsychotics
Antipsychotics
Used to treat psychoses whether
primary or secondary in nature
Divided into two general classes
typical and atypical agents
Side effects generally include
extrapyramidal side effects,
cardiovascular effects, and
anticholinergic effects
TABLE 155-1 -- Selected Antipsychotic Agents Approved or Nearing Approval for Use in
the United States
Category and
medications
Receptors blocked
Clinical effects
Adverse effects
Chlorpromazine
Dopamine D2
(moderate affinity in
both mesolimbic and
nigrostriatal areas)
Extrapyramidal
syndromes
Chloroprothixene
Acetylcholine
muscarinic (generally
strong affinity)
Control positive
symptoms of
psychotic disorders:
Hallucinations
Delusions
Agitation
Disordered thought
Fluphenazine
Histamine H1 (strong
affinity)
Sedation (common)
Hydroxyzine
α-Adrenergic
(moderate affinity)
Orthostatic
hypotension
(common)
Mesoridazine
Dopamine D1 , D3 ,
D4 , D5 (variable
affinity)
Anticholinergic
symptoms
Dry mouth
Blurred vision
Impaired sweating
Constipation
Weight gain
Urinary retention
Angle-closure
Low potency
Molindone
Perphenazine
Prochlorperazine
Promethazine
Thioridazine
Tardive dyskinesia
(common)
High potency
Droperidol
Dopamine D2 (strong
affinity in both
mesolimbic and
nigrostriatal areas)
Haloperidol
Acetylcholine
muscarinic, histamine
H1 , α-adrenergic
(weak affinity)
Tardive
dyskinesia
(common)
Loxapine
Dopamine D1 , D3 ,
D4 , D5 (variable
affinity)
Sedation,
orthostatic
hypotension, and
anticholinergic
symptoms
Pimozide
Thiothixene
Control positive
symptoms of
psychotic disorders
Extrapyramidal
syndromes
(common)
Atypicals
Clozapine
Serotonin 5HT2A
(strong)
Control positive
symptoms of
psychotic disorders
Olanzapine
Dopamine D2 (mild to
moderate affinity,
selective for
mesolimbic areas)
Quetiapine
Dopamine D1 , D3 ,
D4 , D5 (variable
affinity)
Control negative
symptoms of
psychotic disorders:
Social withdrawal
Flattened affect
Avolition (inactivity)
Paucity of speech
Pseudodementia
Risperidone
Sertindole
Extrapyramidal
syndromes and
tardive
dyskinesia
(uncommon)
Typical Antipsychotics
Divided into low potency and high
potency generally differentiated by
side effect profile
Mechanism of action of typical agents
are blockade of D2 receptors in the
basal ganglia, limbic system,
hypothalamus, and chemoreceptor
trigger zone
Antipsychotics
Low Potency versus High Potency
Low potency: significant hypotension
– Rarely used in the ED
High Potency: few anticholinergic
and alpha blocking effects
– Choice Drugs in the ED
– Haldol is only approved for IM use even
though it has been used IV
Atypical Antipsychotics
Developed to minimize the
extrapyramidal side effects of typical
agents
Atypical agents work by a balanced
blockade of D2 and serotonin 5HT2 A
receptors
Extrapyramidal Side Effects
Characteristic
Pyramidal
Extrapyramidal
Anatomy
Precisely demarcated
pathways from cortex to
muscle
Hypothesized pathways
among basal ganglia and
other structures of the
central nervous system
Physiologic movements
Voluntary
Involuntary
Pathologic movements
Paralysis, paresis,
hyperreflexia, and
spasticity
Akathisia, athetosis,
ballism, chorea, dystonia,
myoclonus, stereotypy,
tic, and tremor
Extrapyramidal Side Effects
Akinesia
–lack of movement, Parkinson-like
Dystonic Reaction
–muscle spasms of face, neck, back
Dyskinesia
–Blinking or twitches
Akathesia
–Inability to sit still
Acute Dystonic Reactions
Typically occur in young males during the
initiation of therapy
Symptoms include muscle spasms of the
back, neck, and face occasionally
oculogyric crisis and laryngospasm may
occur
Treatment includes diphenhydramine 50100mg IV/IM or benztropine 1-2mg IV
and airway support if severe
laryngospasm occurs
Akathisia
Typically characterized by a
subjective feeling of restlessness and
inability to stay still
Occurs in ~40 % of patients
receiving 10mg of haloperidol within
an hour or administration
Parkinsonian Syndrome
Symptoms include bradykinesia,
cogwheel rigidity, resting tremor,
and shuffling gait
Occurs with high and low potency
typical agents
Symptoms may be treated with
simultaneous administration an
anticholingeric medication and
lowering the dose of the
antipsychotic
Tardive Dyskinesia
Chronic movement disorder
characterized by involuntary
movements of the face, extremities,
and trunk
Occurs in up to 20% of patents
receiving long term antipsychotics
Generally once symptoms occur
they are permanent however
benztropine may help control
symptoms
Cardiovascular Effects
Hypotension may occur with low potency
typical agents
Prolonged QT and Torsade de Pointes
may occur with any antipsychotic
medication however they occur primarily
with thioridazine, mesoridazine,
droperidol, sertindole, and high-dose IV
haloperidol
Treatment includes discontinuation of the
offending drug, IVF for hypotension, and
treatment of torsade de pointes with
MgSO4 or overdrive pacing
Anticholinergic side effects
• Symptoms include dry mouth,
sedation, urinary retention,
cardiovascular effects, and altered
sensorium
• Management is primary supportive
and includes discontinuation of the
drug and physostigmine 1-2mg IV
only in siezure, coma, and
arrhythmia
Overdose of Antipsychotics
Experience with acute ingestion of
antipsychotics is limited
Given the mechanism of action at the
chemoreceptor trigger zone high doses
induce nausea and emesis and may aid in
elimination of the drug
The most common manifestation is
depressed level of consciousness
Protective airway reflexes are impaired at
high doses
Overdose of Antipsychotics
Treatment includes the ABCs, IV, O2, cardiac
monitoring, administration of activated charcoal
The most common cause of morbidity and
mortality is aspiration pneumonia so intubation
should highly be considered early in the
resuscitation
Hypotension is generally mild and responds to
IVFs
The most common cardiac rhythm is sinus
tachycardia
Treatment of torsade de pointes include MgSO4
or overdrive pacing if no response to MgSO4
Most patients recover from isolated
antipsychotic overdose
Neuroleptic Malignant Syndrome
Idiosyncratic side effect of
antipsychotic medications
Occurs in ~1 in 500 generally within
the first two weeks of therapy, but
may occur anytime
Cardinal features include altered
mental status, muscle rigidity,
hyperthermia, and autonomic
nervous system dysfunction
Lab: elevated CPK, aldolase, WBC,
LFTs
Neuroleptic Malignant Syndrome
NMS is a medical emergency with a
mortality rate approaching 20%
Treatment is primarily supportive
beginning with the ABCs,
discontinuation of the offending
drug, and IV hydration
– Avoid: anticholinergic meds
Multisystem organ failure may occur
with liver and renal dysfunction
being the most commonly involved
Treatment
Antidepressants
Tricyclic Antidepressants
Indications:
–
–
–
–
–
–
–
Major Depression
Dysthmic Disorder
Panic Disorder
Agorophobia
Obscessive Compulsive Disorder
Enuresis
School phobia
Therapeutic Effects:
– Related to norepinephrine and serotonin
Major Pharmacodynamic Effects
of Cyclic Antidepressents
Sodium channel blockade (quinidine-like effects)
– negative inotropism, wide QRS, prolonged QT, AV Block
α1 -Adrenoreceptor blockade
– hypotension
Inhibition of reuptake of biogenic amines
(norepinephrine, serotonin)
– initially hypertensive and tachycardic
Muscarinic receptor blockade
– anticholinergic effects Dry mouth
Dry mouth, flushed skin, blurred vision, urinary retention,
constipation, dizziness, ALOC, emesis
Histamine receptor blockade
– antihistaminic effects
Tricyclic Antidepressants
Anticholinergic side effects are the
most common which include dry
mouth, blurred vision, constipation,
urinary retention, tachycardia, and
altered sensorium
– Aggitation: treat with benzos, avoid
phenothiazines
– Pysostigmine (centrally acting
cholinergic) is contraindicated in TCA:
May cause asystole
Tricyclic Antidepressants
Cardiac effects: EKG changes occur within 6
hours of ingestion
– negative inotropism, wide QRS, prolonged QT, AV block,
atrial and ventricular dysrhythmias
Treatment:
– alkalization and sodium loading
– blood to a pH of 7.45-7.55 appears to uncouple TCA
from myocardial sodium channels
– D5W plus 2 amps of bicarb TRA 100-150 cc/hr
– controlled studies have only validated the benefits of the
initial bolus of 1-2 mEq/kg of sodium bicarbonate
– no controlled studies looking at continuous infusions
– Class IA, IC, b-blockers, Ca-channel blockers, Class III
contraindicated
Tricyclic Antidepressants
Hypotension:
Treat with IVF. If hypotension persists, bicarb is indicated
regardless of QRS width.
Direct acting alpha-agonists (eg, norepinephrine,
phenylephrine) are indicated when significant hypotension
persists despite adequate volume replacement (as
monitored by central venous pressure or pulmonary
capillary wedge pressure).
Dopamine may not be as effective because its action is
mediated by the release of endogenous catecholamines
that may be depleted during TCA toxicity.
In addition, use of dopamine or dobutamine alone may
result in unopposed beta-adrenergic activity resulting from
TCA-induced alpha blockade and, therefore, may worsen
hypotension.
Tricyclic Antidepressants
TCA-induced seizures should be treated
aggressively
– Acidosis: augmenting cardiovascular toxicity
– Goal of 7.45-7.55 pH with Bicarb
administration
Benzodiazepines: Drug of Choice
– Phenytoin: ineffective / possible
prodysrhythmic effects
– Phenobarbital second line
– Physostigmine is contraindicated
– Flumazenil is contraindicated
– Bicarb does not stop siezures
– Neuromuscular blockers / General
Tricyclic Antidepressants
Overdose of tricyclics accounts for up to
20% of deaths from suicidal ingestion
Poor outcome is associated with QRS>100
msec, hypotension, cardiac dysrhythmias,
and acidemia
Treatment includes the ABCs, IVFs, O2,
monitor, activated charcoal, and HCO3 if
acidemia or QRS>100 is present
Monoamine Oxidase Inhibitors
Although infrequently used MAOIs
are indicated for atypical depression
and refractory depression
unresponsive to TCAs or SSRIs
Mechanism of action related to
increased serotonin and
norepinephrine in the CNS
Monoamine Oxidase Inhibitors
Side effects include orthostatic hypotension which
may be severe, CNS irrability, and anticholinergic
side effects
Tyramine/Hypertensive crisis may occur when
sympathomimetic drugs, L-dopa, narcotics, TCAs,
or tyramine containing foods such as aged
cheese, wine, pickled herring, fava beans are
ingested
– Onset is usually precipitated by a severe headache and
may progress to a hypertensive ICH with subsequent
death
– However most patients have resolution of symptoms
within a few hours and their medications may be
restarted with counseling concerning drug interactions
Serotonin Selective Reuptake
Inhibitors
The most common class of
antidepressants prescribed due to
their high therapeutic index and
lower side effect profile
Indicated for major depressive
disorder, panic disorder, generalized
anxiety disorder, and OCD
Serotonin Selective Reuptake
Inhibitors
Side effects include headache,
dizziness, nausea, diarrhea,
insomnia, and sexual dysfunction
Sudden withdrawal of SSRIs may
present as flu like symptoms
including nausea, fatigue, myalgias,
vertigo, and headache
– Treatment is reinstatement of SSRI and
gradual tapering
Serotonin Selective Reuptake
Inhibitors
Serotonin syndrome characterized by
CNS, GI, and occasionally
cardiovascular symptoms
(restlessness, tremor, myoclonus,
hyperreflexia, and siezures)
It is clinically indistinguishable from
NMS
Treatment is mainly supportive
including the ABCs, IVF, O2, cardiac
monitoring, activated charcoal, and if
symptoms persist hemodialysis
Anxiolytics
Anxiolytics
Indicated for short term management of anxiety or acute
panic reactions
Mechanism of action is related to binding of to the
benzodiazepine receptor
Side effects generally are CNS related such as drowsiness,
sedation, and ataxia
In acute overdose of benzodiazepine careful respiratory
monitoring should take place with standard therapy
initiated with careful attention to possible mixed ingestions
Flumenazil is only indicated with single benzodiazepine
overdose and not with mixed overdose
– The only time flumenazil should be administered is if the
treating physician administers too much benzodiazepine
References
Marx, John MD Rosen's Emergency
Medicine: Concepts and Clinical
Practice, 5th ed, Mosby, 2002
Tintinalli, Judith MD Emergency
Medicine:A Comprehensive Study
Guide, 5th ed, McGraw-Hill, 2000
Merck Manual
Questions?