II. Definitions

  1. Dinitrophenol (DNP)
    1. Organic substances, phenols with 2 attached nitro groups

III. Background

  1. DNP has been used to produce explosives (e.g. Shellite, Tridite), and in production of black dye
    1. Fatal, accidental Poisonings have occurred in manufacturing workers
  2. 2,4 DNP has been used in humans
    1. This article refers specifically to 2,4 DNP toxicity (adverse effects, labs, management)
    2. Used by the Russian Red Army in World War 2 to promote cold hardiness
    3. Blocks lipogenesis, and was used as a weight loss agent in U.S. until it was banned by the FDA in 1938
    4. Has been on and off the 1972 Poisons List (pending possible reinsertion into that list as of 2021)
    5. Illicit use by body builders continues (obtained online)

IV. Mechanism

  1. Uncouples Oxidative Phosphorylation, blocking ATP formation
  2. Increases intracellular Calcium, resulting in increased Muscle Contraction and heat generation

V. Pharmacokinetics

  1. Rapidly absorbed from intestinal tract (as well as inhaled or absorbed through skin)
  2. Toxic dose: 1-3 mg/kg
  3. Half-Life: Days
  4. Hepatic metabolism

VI. Adverse Effects

  1. Acute Hypermetabolic State (may be lethal)
    1. Hyperthermia, Tachycardia, Tachypnea, Diaphoresis
    2. Muscle spasms to Rhabdomyolysis
    3. Acute Renal Failure
    4. Metabolic Acidosis
    5. Altered Mental Status, Agitation, Seizures
  2. Longterm effects
    1. Cataract rapid development

VII. Labs

  1. See Unknown Ingestion for complete toxicology workup
  2. Comprehensive Metabolic Panel
    1. Metabolic Acidosis with Anion Gap
    2. Acute Kidney Injury
  3. Creatine Phosphokinase (CPK)
    1. Rhabdomyolysis

VIII. Management

  1. Detoxification
    1. Activated Charcoal if presentation within one hour of large ingestion
  2. Intravenous Fluids
  3. Agitation or Seizures
    1. Benzodiazepines
  4. Hyperthermia
    1. External cooling
    2. Dantrolene
  5. Disposition
    1. May medically clear if asymptomatic at 10-12 hours after ingestion
    2. Observe all symptomatic ingestions, especially with hypermetabolic symptoms (e.g. Tachycardia, hyperthermia)

IX. Resources

X. References

  1. Tomaszewski (2022) Crit Dec Emerg Med 36(10): 32

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