Neuroleptic Agent Toxicity Medication

  • Author: Kathryn Ruth Challoner, MD, MPH, FACEP; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Jun 23, 2010
 

Medication Summary

No specific antidotes exist for the adverse effects of neuroleptic medications. Because these effects are so diverse and do not occur in most cases, prophylactic treatment for seizures, dystonia, dysrhythmias, or NMS is not indicated.

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GI decontaminants

Class Summary

Empirically used to minimize systemic absorption of the toxin. May only be of benefit if administered within 1-2 h of ingestion.

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Activated charcoal (Liqui-Char)

 

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.

For maximum effect, administer within 30 min of ingesting poison.

Generally mixed and administered with a saline cathartic (do not use sorbitol).

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Anticonvulsants

Class Summary

Indicated for seizures and status epilepticus associated with major tranquilizer overdose. Compared to lorazepam, advantages of diazepam are more rapid onset of action and decreased cost. The disadvantage is that diazepam has a brief duration of anticonvulsant activity (20 min) compared to lorazepam (several hours). Both drugs can aggravate hypotension, which may limit their usefulness in this setting.

Barbiturates are usually not necessary in neuroleptic overdose because most patients respond to benzodiazepines. Phenobarbital is the most commonly used anticonvulsant, but shorter-acting barbiturates are also effective.

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Diazepam (Valium)

 

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.

Seizures are relatively common in association with major tranquilizer overdose because most neuroleptics lower seizure threshold. In the ED, standard protocol is used for terminating seizures.

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Lorazepam (Ativan)

 

Sedative hypnotic with short onset of effects and relatively long half-life.

By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

Monitoring blood pressure after administering dose is important. Adjust prn.

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Midazolam (Versed)

 

Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access

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Phenobarbital (Barbita, Luminal)

 

Interferes with transmission of impulses from thalamus to cortex of brain. Effective in terminating convulsions, but use is often limited by hypotension associated with neuroleptic overdose.

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Cardiovascular agents

Class Summary

Use of direct-acting alpha-agonists is preferred when hypotension persists after adequate volume challenge with isotonic sodium chloride solution IV. Pressors with actions at beta- and alpha-receptors (eg, dopamine, epinephrine) may exert only a beta (vasodilatory) effect in the face of neuroleptic-induced alpha blockade; consequently, a paradoxical drop in blood pressure may occur if the pressors are used.

Dysrhythmias are relatively common in neuroleptic overdose. Prolongation of the QT interval may result in torsade de pointes. The quinidinelike effect on the slope of phase 0 of the ECG may result in widening of the QRS. Magnesium may be an effective treatment.

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Norepinephrine (Levophed)

 

Stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility, heart rate, and vasoconstriction. As a result, systemic blood pressure and coronary blood-flow increases.

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Magnesium sulfate

 

Currently DOC for treatment of torsade de pointes and may be an effective antiarrhythmic for ventricular and supraventricular tachycardia.

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Skeletal muscle relaxant

Class Summary

Dantrolene is currently recommended as treatment for hyperthermia associated with neuroleptic malignant syndrome. Acts to restore calcium entry into muscle sarcoplasmic reticulum, causing muscle relaxation and decreasing heat production from muscle.

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Dantrolene (Dantrium)

 

Stimulates muscle relaxation by modulating skeletal muscle contractions at site beyond myoneural junction and acting directly on muscle itself.

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Antihistamines

Class Summary

Agents with anticholinergic properties are effective in terminating acute dystonias associated with neuroleptic use.

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Diphenhydramine (Benadryl)

 

Anticholinergic medications help restore balance between dopaminergic and cholinergic neurotransmission. Dopaminergic transmission is decreased by neuroleptic drugs.

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Dopamine agonist

Class Summary

Can reverse the dopamine blockade caused by neuroleptics and has been reported to be useful in reversing NMS symptoms.

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Bromocriptine (Parlodel)

 

Semisynthetic ergot alkaloid derivative. Strong D2-receptor agonist, partial D1-receptor agonist. Stimulates dopamine receptors in corpus striatum.

Approximately 28% absorbed from the GI tract and metabolized in the liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine.

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Amantadine (Symmetrel)

 

Inhibits N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine release in rat striatum. May enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity.

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Contributor Information and Disclosures
Author

Kathryn Ruth Challoner, MD, MPH, FACEP  Clinical Professor of Emergency Medicine, Department of Emergency Medicine, Keck School of Medicine of the University of Southern California

Kathryn Ruth Challoner, MD, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Edward J Newton, MD, FACEP, FRCPC  Professor of Clinical Emergency Medicine, Chairman, Department of Emergency Medicine, University of Southern California Keck School of Medicine

Edward J Newton, MD, FACEP, FRCPC is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Royal College of Physicians and Surgeons of Canada, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Peter MC DeBlieux, MD  Professor of Clinical Medicine and Pediatrics, Section of Pulmonary and Critical Care Medicine, Program Director, Department of Emergency Medicine, Louisiana State University School of Medicine in New Orleans

Peter MC DeBlieux, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Radiological Society of North America, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP  Director of Medical Toxicology, Allegheny General Hospital

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD  Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

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