Dinitrophenol toxicity

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Background

  • Used in the manufacture of munitions, as a dye, a wood preserver, herbicide and photograph developer
    • Can lead to unintentional exposures
  • Discovered as a weight loss drug in 1930's but banned by FDA soon afterwards due to side effects
  • Now banned in US and UK as weight loss drug, labeled "not fit for human consumption"
  • Able to purchase DNP online in mass quantities[1]
    • Typically used by body builders for weight loss
    • Suicidal intentional ingestion
    • Increase in number of deaths in recent years
  • Case reports indicate that 20–50mg per kilogram of body weight in humans can be lethal[2]

Pharmacology

  • Uncouples oxidative phosphorylation
    • Allows increase in basal leak of protons (H+) accross the mitochondrial membrane which is dissipated as heat and leads to hyperthermia
  • Stimulation of glycolysis in small doses

Clinical Features

Very narrow therapeutic window

"Theraputic dose"

  • Pruritic rash
  • Yellow discoloration of skin, eyes, and urine (appears similar to jaundice)
  • Peripheral neuropathy
  • anorexia
  • confusion
  • cataracts
  • deafness
  • coma

Acute toxicity

  • Profuse diaphoresis
  • Hyperthermia
  • Tachypnia
  • Tachycardia
  • Irregular pulse
  • Agitation
  • Headaches
  • Dizziness
  • Blurry vision
  • Confusion
  • Restlessness
  • Dehydration
  • Thirst
  • Flushed skin
  • Cyanosis
  • Abdominal pain
  • Nausea
  • Vomiting
  • Diarrhea
  • Muscular spasms
  • Mayalgia
  • Pulmonary edema
  • Trismus
  • Cytotoxic cerebral edema
  • Acute congestion of the liver
  • Convulsions
  • Coma
  • Shock/cardiovascular collapse
  • PEA/death

Differential Diagnosis

Fever

Infectious

Non-infectious

Toxicologic causes of Hyperthermia

Endocrine causes of Hyperthermia

Neurologic causes of Hyperthermia

Evaluation

High clinical suspicion needed"

Management

  • Decontamination with removal of clothing and irrigation as needed
  • Constant body temperature monitoring, cardiac monitor, IV access, and code cart to bedside
  • Activated charcoal if within 1 hour of ingestion
    • No evidence for or against multiple doses of charcoal or whole bowel irrigation
  • Aggressive IVF administration (cooled if possible)
  • Vasopressors with cardiovascular collapse non-responsive to IVF
  • Treat methemoglobinemia as needed

Hyperthermia

  • External cooling with blankets, ice, and cooling devices
  • Cool IVF
  • Control agitation (adds to hyperthermia)

Agitation

  • Benzodiazepines should be administered as needed
    • Paralyze and intubate if not controlled, but maintain continuous and aggressive sedation
  • Dantrolene has been used to manage DNP hyperthermia[3]

Disposition

  • Admission for most patients
  • Observation if stable

See Also

External Links

References

  1. Grundlingh, Johann, Paul I. Dargan, Marwa El-Zanfaly, and David M. Wood. "2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death." Journal of Medical Toxicology J. Med. Toxicol. 7.3 (2011): 205-12. Web.
  2. Hsiao AL et al. "Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement"". Clin Toxicol (Phila). 2005. 43(4): 281–285.
  3. Kumar S, Barker K, Seger D. Dinitrophenol-induced hyperthermia resolving with dantrolene administration. Clin Toxicol. 2002;40:599-673.