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Dinitrophenol toxicity
From WikEM
Contents
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
- Convulsions
- Shock/cardiovascular collapse
- PEA/death
Differential Diagnosis
Fever
Infectious
- Critical
- Sepsis
- PNA with respiratory failure
- Peritonitis
- Meningitis
- Cavernous Sinus Thrombosis
- Necrotizing Fasciitis
- Emergent
- PNA
- Peritonsillar Abscess
- Retropharyngeal Abscess
- Epiglottitis
- Endocarditis
- Pericarditis
- Appendicitis
- Cholecystitis
- Diverticulitis
- Intra-abdominal abscess
- Pyelonephritis
- Tubo-ovarian abscess
- Encephalitis
- Brain abscess
- Cellulitis
- Abscess
- Malaria
- Non-emergent
Non-infectious
- Critical
- Emergent
- CHF
- Dehydration
- Recent Seizure
- Sickle Cell Dz
- Transplant rejection
- Pancreatitis
- DVT
- Serotonin Syndrome
- Non-emergent
- Drug fever (except as in NMS, Serotonin Syndrome)
- Malignancy
- Gout
- Sarcoidosis
- Crohn's Disease
- Postmyocardiotomy sy
Toxicologic causes of Hyperthermia
- Serotonin syndrome
- Neuroleptic malignant syndrome
- Excited delirium syndrome
- Sympathomimetic toxicity
- Anticholinergic toxicity
- Alcohol withdrawal/Delirium tremens
- Lithium toxicity
- Salicylate toxicity
- TCA toxicity
- Laundry detergent pod ingestion
- Malignant hyperthermia
- Dinitrophenol toxicity
Endocrine causes of Hyperthermia
Neurologic causes of Hyperthermia
Evaluation
High clinical suspicion needed"
- Blood glucose
- CBC
- Chemistry
- Arterial blood gas or Venous blood gas
- Co-oximetry to evaluate for methemoglobinemia
- Lactate
- Coagulation studies
- Creatine phosphokinase
- Urine analysis
- ECG
- Chest x-ray
- CT brain and/orLP as 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
- ↑ 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.
- ↑ Hsiao AL et al. "Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement"". Clin Toxicol (Phila). 2005. 43(4): 281–285.
- ↑ Kumar S, Barker K, Seger D. Dinitrophenol-induced hyperthermia resolving with dantrolene administration. Clin Toxicol. 2002;40:599-673.
