Disulfiram Toxicity Medication
- Author: Samara Soghoian, MD, MA; Chief Editor: Asim Tarabar, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
GI decontaminant
Class Summary
These agents are empirically used to minimize systemic absorption of the toxin.
Activated charcoal (Liqui-Char)
Most useful if administered within 90 min of ingestion. Repeat doses may be used, especially with ingestion of sustained-release agents. Limited outcome studies exist, especially when administration is more than 1 h postingestion.
Administration of charcoal by itself (in aqueous solution), as opposed to coadministration with a cathartic, is becoming the current practice standard. This is because studies have not shown benefit from cathartics, and, while most drugs and toxins are absorbed within 30-90 min, laxatives take hours to work. Dangerous fluid and electrolyte shifts have occurred when cathartics are used in small children.
When ingested dose is known, charcoal may be administered at 10 times ingested dose of agent, over 1 or 2 doses.
Cardiovascular agents
Class Summary
Treat hypotensive patients with IV crystalloid (eg, 0.9 NS or LR). If pressors are indicated, norepinephrine (Levophed) is DOC (over dopamine) because of catecholamine depletion.
Norepinephrine (Levophed)
Used in protracted hypotension following adequate fluid-volume replacement. 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 increase.
After obtaining a response, adjust rate of flow to and maintain at a low normal blood pressure (eg, 80-100 mm Hg systolic), sufficient to perfuse vital organs.
Antihistamines
Class Summary
Antihistamine improves the flushing response in DER. Diphenhydramine (H1 blocker) and cimetidine or ranitidine (H2 blockers) may be beneficial. NSAIDs (eg, Toradol) may ameliorate flushing response by blocking the synthesis of prostaglandins.
Diphenhydramine (Benadryl)
H1-receptor blocker with antiparkinsonism, antiemetic, and anticholinergic response.
Used for symptomatic relief of symptoms caused by histamine released in response to allergens.
Cimetidine (Tagamet)
H2 antagonist that, when combined with an H1 type, may be useful for treating itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis that do not respond to H1 antagonists alone. Use in addition to H1 antihistamines.
Ranitidine (Zantac)
H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Pharmacologic Antidotes
Class Summary
NSAIDs may benefit by reducing the severity of the flushing response. Pyridoxine (vitamin B-6) may be useful in patients who demonstrate evidence of neurological toxicity or intractable seizures.
Ketorolac (Toradol)
Inhibits prostaglandin synthesis by decreasing the activity of cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Pyridoxine (Nestrex)
Used in the treatment of pyridoxine-dependent seizures. Involved in synthesis of GABA within CNS.
Antiemetics
Class Summary
These agents are useful in cases of vomiting to mitigate symptoms and to avoid volume depletion.
Metoclopramide (Reglan)
A promotility agent that increases gastric contractions, relaxes the pyloric sphincter and duodenal bulb, and increases peristalsis in the duodenum and jejunum. Exact mechanism is unknown, but metoclopramide may increase gastric emptying and decrease intestinal transit time by sensitizing tissues to the effects of acetylcholine. Has little or no effect on gastric, biliary, or pancreatic secretions, or on colon or gallbladder motility.
Ondansetron (Zofran)
Selective antagonist of serotonin 5HT3 receptors generally used to control chemotherapy-associated and postoperative nausea and vomiting. Precise mechanism of action is not known; however, ondansetron is thought to block either vagal stimulation of serotonin release in the central chemoreceptor trigger zone of the area postrema, or a vagally mediated vomiting reflex caused by release of serotonin from enterochromaffin cells of small intestine and stimulation of peripheral 5HT3 receptors, or both.
Granisetron (Kytril)
An antinauseant and antiemetic available in PO and IV forms for use in severe postoperative and chemotherapy/radiation therapy-induced nausea. Granisetron is a selective antagonist of serotonin 5HT3 receptors. Precise mechanism of action not known; however, thought to block either vagal stimulation of serotonin release in central chemoreceptor trigger zone of area postrema, or a vagally mediated vomiting reflex caused by release of serotonin from enterochromaffin cells of small intestine and stimulation of peripheral 5HT3 receptors.
Baker JR, Jatlow P, McCance-Katz EF. Disulfiram effects on responses to intravenous cocaine administration. Drug Alcohol Depend. Mar 16 2007;87(2-3):202-9. [Medline].
Vaccari A, Ferraro L, Saba P, et al. Differential mechanisms in the effects of disulfiram and diethyldithiocarbamate intoxication on striatal release and vesicular transport of glutamate. J Pharmacol Exp Ther. Jun 1998;285(3):961-7. [Medline].
Filosto M, Tentorio M, Broglio L, et al. Disulfiram neuropathy: two cases of distal axonopathy. Clin Toxicol (Phila). Apr 2008;46(4):314-6. [Medline].
Burman WJ, Terra M, Breese P, et al. Lack of toxicity from concomitant directly observed disulfiram and isoniazid-containing therapy for active tuberculosis. Int J Tuberc Lung Dis. Sep 2002;6(9):839-42. [Medline].
Milne HJ, Parke TR. Hypotension and ST depression as a result of disulfiram ethanol reaction. Eur J Emerg Med. Aug 2007;14(4):228-9. [Medline].
de Mari M, De Blasi R, Lamberti P, et al. Unilateral pallidal lesion after acute disulfiram intoxication: a clinical and magnetic resonance study. Mov Disord. Apr 1993;8(2):247-9. [Medline].
Ellenhorn MJ. Disulfiram. In: Ellenhorn's Medical Toxicology. Vol 2. Lippincott Williams & Wilkins; 1997:1356-62.
Enghusen Poulsen H, Loft S, Andersen JR, et al. Disulfiram therapy--adverse drug reactions and interactions. Acta Psychiatr Scand Suppl. 1992;369:59-65; discussion 65-6. [Medline].
Forns X, Caballeria J, Bruguera M, et al. Disulfiram-induced hepatitis. Report of four cases and review of the literature. J Hepatol. Nov 1994;21(5):853-7. [Medline].
Heath MJ, Pachar JV, Perez Martinez AL, et al. An exceptional case of lethal disulfiram-alcohol reaction. Forensic Sci Int. Sep 1992;56(1):45-50. [Medline].
Hirschberg M, Ludolph A, Grotemeyer KH, et al. Development of a subacute tetraparesis after disulfiram intoxication. Case report. Eur Neurol. 1987;26(4):222-8. [Medline].
Kirubakaran V, Faiman MD, Liskow B, et al. Plasma measurements of disulfiram and its metabolites in a case of severe disulfiram-ethanol reaction. Psychiatr J Univ Ott. Sep 1986;11(3):166-8. [Medline].
Krauss JK, Mohadjer M, Wakhloo AK, et al. Dystonia and akinesia due to pallidoputaminal lesions after disulfiram intoxication. Mov Disord. 1991;6(2):166-70. [Medline].
Kuffner EK. Disulfiram and disulfiram-like reactions. In: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS. Goldfrank's Toxicology Emergencies. 8th ed. McGraw-Hill; 2006:1176-1183.
Laplane D, Attal N, Sauron B, et al. Lesions of basal ganglia due to disulfiram neurotoxicity. J Neurol Neurosurg Psychiatry. Oct 1992;55(10):925-9. [Medline].
Mahajan P, Lieh-Lai MW, Sarnaik A, et al. Basal ganglia infarction in a child with disulfiram poisoning. Pediatrics. Apr 1997;99(4):605-8. [Medline].
Nasrallah HA. Vulnerability to disulfiram psychosis. West J Med. Jun 1979;130(6):575-7. [Medline].
Stransky G, Lambing MK, Simmons GT, et al. Methemoglobinemia in a fatal case of disulfiram-ethanol reaction. J Anal Toxicol. Mar-Apr 1997;21(2):178-9. [Medline].
Zorzon M, Mase G, Biasutti E, et al. Acute encephalopathy and polyneuropathy after disulfiram intoxication. Alcohol Alcohol. Sep 1995;30(5):629-31. [Medline].
Print
