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Valproic acid toxicity: overview and management.

Matthew D Sztajnkrycer1

  • 1Department of Emergency Medicine, University of Cincinnati Medical Center, Ohio, USA. stajnkrycer.matthew@mayo.edu

Journal of Toxicology. Clinical Toxicology
|December 12, 2002
PubMed
Summary

Valproic acid overdose is a growing concern. This review covers its pharmacology, toxicology, and management, highlighting CNS depression and metabolic issues.

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Area of Science:

  • Pharmacology and Toxicology
  • Neuroscience
  • Clinical Medicine

Background:

  • Valproic acid (VPA) intoxication is an increasing public health issue, with over 5000 calls to poison control centers in 2000.
  • VPA is an antiepileptic agent with a unique mechanism of action, distinct from other antiepileptic drugs.
  • Understanding VPA's pharmacology and toxicology is crucial for managing overdose cases.

Purpose of the Study:

  • To review the pharmacology and toxicology of valproic acid toxicity.
  • To elucidate the mechanism of action of valproic acid, particularly its indirect effect on gamma-aminobutyric acid (GABA) levels.
  • To discuss the diverse clinical manifestations and management strategies for acute valproic acid intoxication.

Main Methods:

  • Literature review of pharmacology and toxicology of valproic acid.
  • Analysis of clinical manifestations and metabolic derangements associated with valproic acid overdose.
  • Discussion of supportive care and adjunctive therapies for valproic acid toxicity.

Main Results:

  • Valproic acid toxicity manifests through exaggerated therapeutic effects and impaired intermediary metabolism.
  • Central nervous system depression, progressing to coma and respiratory depression, is the most common finding.
  • Other reported issues include cerebral edema, pancreatitis, hyperammonemia, and metabolic/hematologic derangements.

Conclusions:

  • Management of acute valproic acid ingestion necessitates supportive care, airway management, and monitoring for complications.
  • The review discusses controversial adjunctive therapies such as extracorporeal drug elimination and L-carnitine supplementation.
  • Further research may be needed to optimize treatment strategies for valproic acid overdose.

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