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Research ArticlePerspectives in Pharmacology

Experimental Treatments for Cocaine Toxicity: A Difficult Transition to the Bedside

Nicholas J. Connors and Robert S. Hoffman
Journal of Pharmacology and Experimental Therapeutics November 2013, 347 (2) 251-257; DOI: https://doi.org/10.1124/jpet.113.206383
Nicholas J. Connors
Division of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, Bellevue Hospital Center, New York, New York
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Robert S. Hoffman
Division of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, Bellevue Hospital Center, New York, New York
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Abstract

Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. Although there is no true antidote to cocaine toxicity, current management strategies address the life-threatening systemic effects, namely hyperthermia, vasospasm, and severe hypertension. Clinicians rely on rapid cooling, benzodiazepines, and α-adrenergic antagonists for management, with years of proven benefit. Experimental agents have been developed to more effectively treat acute toxicity. Pharmacodynamic approaches include antipsychotics that are thought to interfere with cocaine’s actions at several neurotransmitter receptors. However, these medications may worsen the consequences of cocaine toxicity as they can interfere with heat dissipation, cause arrhythmias, and lower the seizure threshold. Pharmacokinetic approaches use cocaine-metabolizing enzymes, such as butyrylcholinesterase (BChE), cocaine hydrolase (CocH), and bacterial cocaine esterase (CocE). Experimental models with these therapies improve survival, primarily when administered before cocaine, although newer evidence demonstrates beneficial effects shortly after cocaine toxicity has manifested. CocE, a foreign protein, can induce an immune response with antibody formation. When enzyme administration was combined with vaccination against the cocaine molecule, improvement in cocaine-induced locomotor activity was observed. Finally, lipid emulsion rescue has been described in human case reports as an effective treatment in patients with hemodynamic compromise because of cocaine, which correlates well with its documented benefit in toxicity due to other local anesthetics. A pharmaceutical developed from these concepts will need to be expedient in onset and effective with minimal adverse effects while at the same time being economical.

Footnotes

    • Received May 20, 2013.
    • Accepted August 26, 2013.
  • dx.doi.org/10.1124/jpet.113.206383.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 347 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 347, Issue 2
1 Nov 2013
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Research ArticlePerspectives in Pharmacology

Experimental Treatments for Cocaine Toxicity

Nicholas J. Connors and Robert S. Hoffman
Journal of Pharmacology and Experimental Therapeutics November 1, 2013, 347 (2) 251-257; DOI: https://doi.org/10.1124/jpet.113.206383

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Research ArticlePerspectives in Pharmacology

Experimental Treatments for Cocaine Toxicity

Nicholas J. Connors and Robert S. Hoffman
Journal of Pharmacology and Experimental Therapeutics November 1, 2013, 347 (2) 251-257; DOI: https://doi.org/10.1124/jpet.113.206383
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