Antipsychotics Toxicity


Antipsychotics were developed for the treatment of psychoses, but are also commonly used in the treatment of N/V, migraines, and to control the agitated patient.

Therapeutic effects are due to antagonism of mesolimbic dopamine receptors, but variable affinity for other receptors causes a variety of side effects and toxicity in therapeutic use.

They are divided into two major groups (see Table below):
TYPICAL ANTIPSYCHOTICS ATYPICAL ANTIPSYCHOTICS
Characterized by less receptor specificity → greater incidence of side effects than newer agents The newer generation medications, first introduced in the 1990s. Acute overdose is common, but toxicity resulting in severe morbidity or mortality is rare.
Haloperidol (Haldol)
Chlorpromazine (Thorazine)
Promethazine (Phenergan)
Proclorperazine (Compazine)
Risperidone (Risperdal)
Quitiapine (Seroquel)
Olanzapine (Zyprexa)
Olanzapine (Zyprexa)

MECHANISM/TOXICITY

SYMPTOMS/EXAM

DIAGNOSIS

ED CARE AND DISPOSITION

  1. Supportive therapy, IV Access, Cardiac monitoring.
  2. Ventilatory support may be necessary for pts with respiratory depression.
  3. Activated charcoal: For large ingestions within 1-2 hours (with airway protection as needed)
  4. IV magnesium sulfate 2-4 g IV, overdrive pacing, isoproterenol for torsades
  5. Interventricular conduction delay & interval dysrhythmias:
  6. Norepinephrine: For hypotension unresponsive to IVF
  7. Benzodiazepines: To control agitation and seizures
  8. Neuroleptic Malignant Syndrome:
  9. Observe pt for 6 hr post-ingestion. Admit symptomatic pts to a monitored bed. Pt with neuroleptic malignant syndrome warrant ICU admission.

 


Adverse Effects of Antipsychotics

ADVERSE EFFECT MECHANISM/TOXICITY SYMPTOMS/EXAM TREATMENT
Extrapyramidal Symptoms Basal ganglia dopamine receptor antagonism
 
 See Table 6.13 below  
Neuroleptic Malignant Syndrome Anterior hypothalamus & basal ganglia dopaine receptor antagonism AMS
Hypothermia
Muscular rigidity
-Stop Medication
-Benzodiazepines
-Intubate & paralyze as needed
AMS Histamine & muscurinic receptor antagonism Agitated delirium
Somnolence
Coma
-Benzodiazepines for agitation
-Support airway prn.
Hypotension Alpha1-adrenergic receptor antagonism Mild to moderate hypotension -IV fluids
- Pressors may be needed
Tachycardia Alpha1-adrenergic (reflex tachycardia) & muscurinic receptor antagonism Mild to Moderate Tachycardia  
Prolonged qTc K channel blockade Thermoretical concern for torsades de pointes, but rare -Cardiac monitoring
-Check electrolytes
-Treat torsades using standard therapies.
Blood Dyscrasias Adverse drug effect associated with clozaril Agranulocytosis
Leukopenis
Neutropenia
- Stop Medication

Extrapyramidal Symptoms

NAME ONSET/REVERSIBILITY SYMPTOMS/EXAM TREATMENT
Akathisia Hours to days
Reversible
Anxiety
Acute Motor restlessness
STOP medication
Benzodiazepine
Benadryl
Acute dystonia Hours to days after exposure
Reversible
Sustained muscle contraction
Facial gtimacing.
Torticollis
Trismus
Laryngospasm
Opisthotonos
STOP medication
Benzodiazepine
Benadryl
 
Parkinsonism Days to months of exposure
Usually reversible
Akinesia or bradykinesia
Masked facies
Muscular rigidity
Tremor
Gait instability
Cognitive impairment
↓ Dose or stop medication

Benztropine
Tardive dyskinesia Months to years of exposure
Usually irreversible
Involuntary, repetitive orofacial, trunk & extremity movements No specific treatment available.