Dinitrophenol toxicity: Difference between revisions
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==Clinical Features== | ==Clinical Features== | ||
''Very narrow therapeutic window'' | ''Very narrow therapeutic window'' | ||
==="Theraputic dose"=== | |||
*Pruritic rash | *Pruritic rash | ||
*Yellow discoloration of skin, eyes, and urine (appears similar to [[jaundice]]) | *Yellow discoloration of skin, eyes, and urine (appears similar to [[jaundice]]) | ||
Line 26: | Line 26: | ||
*deafness | *deafness | ||
*coma | *coma | ||
===Acute toxicity=== | |||
*Profuse diaphoresis | *Profuse diaphoresis | ||
*Hyperthermia | *Hyperthermia | ||
*Tachypnia | *Tachypnia | ||
*Tachycardia | *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 | *Convulsions | ||
*Coma | |||
*Shock/cardiovascular collapse | *Shock/cardiovascular collapse | ||
*PEA/death | *PEA/death | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
{{ | {{Differential diagnosis hyperthermia}} | ||
==Evaluation== | ==Evaluation== | ||
Line 48: | Line 71: | ||
*Coagulation studies | *Coagulation studies | ||
*Creatine phosphokinase | *Creatine phosphokinase | ||
*Urine analysis | *[[Urine analysis]] | ||
*[[ECG]] | *[[ECG]] | ||
*Chest x-ray | *[[Chest x-ray]] | ||
*CT brain and/or[[LP]] as needed | *[[CT brain]] and/or[[LP]] as needed | ||
==Management== | ==Management== | ||
*Decontamination with removal of clothing and irrigation as needed | *Decontamination with removal of clothing and irrigation as needed | ||
*Constant body temperature monitoring, cardiac monitor, IV access, and code cart to bedside | *Constant body temperature monitoring, cardiac monitor, IV access, and code cart to bedside | ||
*Activated charcoal if within 1 hour of ingestion | *[[Activated charcoal]] if within 1 hour of ingestion | ||
**No evidence for or against multiple doses of charcoal or whole bowel irrigation | **No evidence for or against multiple doses of charcoal or whole bowel irrigation | ||
*Aggressive [[IVF]] administration (cooled if possible) | *Aggressive [[IVF]] administration (cooled if possible) | ||
Line 80: | Line 103: | ||
==External Links== | ==External Links== | ||
*[https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAttachment.aspx?Attachment_id=103205 Public Health England - DNP (2,4 dinitrophenol) toxicity] | |||
*[https://www.atsdr.cdc.gov/ToxProfiles/tp64.pdf DHHS - Toxicological Profile for Dinitrophenols] | |||
*[https://aapcc.org/annual-reports AAPCC - National Poison Data System Annual Reports] | |||
==References== | ==References== | ||
[[Category:Toxicology]] | [[Category:Toxicology]] |
Latest revision as of 17:13, 18 May 2020
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
- 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 and Serotonin Syndrome)
- Malignancy
- Gout
- Sarcoidosis
- Crohn's Disease
- Postmyocardiotomy syndrome
- Sweet's syndrome
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
- Public Health England - DNP (2,4 dinitrophenol) toxicity
- DHHS - Toxicological Profile for Dinitrophenols
- AAPCC - National Poison Data System Annual Reports
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.