2,4-Dinitrophenol overdose - Everything old is new again.

A complete case example of a fatal 2,4-dinitrophenol (DNP) overdose involving a 23-year-old male is described. Included are details of not only the patient's presentation symptoms and treatment, but also the subsequent findings of the coronial investigation process including the autopsy, post-mortem computed tomography (PMCT) scanning and toxicological analysis and results. The patient presented with elevated temperature, heart rate and blood pressure. Multiple treatments were conducted to counteract these symptoms, however the patient died approximately 1.5 hours after hospital admission and some 4.5 hours after the DNP was initially consumed. Autopsy revealed the presence of cardiovascular disease that was contributory to death and post-mortem computed tomography showed evidence of decompositional intravascular gas in the neck, head, face, lower abdomen, heart and hepatic systems. Toxicological analysis was completed by protein precipitation with methanol and subsequent instrumental analysis by LC/MS/MS in negative ion mode. The antemortem blood specimen showed the presence of tadalafil, two anabolic steroids and a DNP concentration of 110 mg/kg which is consistent with other reported DNP fatalities. Despite the small amount of time between the antemortem specimen collection and death, the DNP concentration identified in the femoral blood post-mortem specimen was comparably low (5.5 mg/kg). DNP concentrations also reduced during an extended period of specimen storage prior to analysis indicating some instability in biological specimens even when refrigerated or frozen. DNP was found to be distributed primarily in the aqueous tissues (blood, vitreous, bile) rather than solid matrices (liver, kidney, muscle).

Bodybuilding supplements leading to copper toxicity, encephalopathy, fulminant hepatic failure and rhabdomyolysis.

Millions of people worldwide use nutritional and dietary supplements, such as vitamins and minerals. These and other performance-enhancing substances are also used by high school, college, and professional athletes, bodybuilders, and amateur sports enthusiasts. The constituents of these supplements and their metabolites may be harmful and not listed on the product label. We present a case report of a 32-year-old bodybuilder using myriad nutritional, performance-enhancing, and weight-loss supplements with life-threatening encephalopathy, hepatic failure, rhabdomyolysis, and copper toxicity mimicking Wilson's disease. Emergency physicians and nurses should be aware of these potential deleterious effects and inquire about supplement use by patients with unexplained multiorgan failure. Family, friends, or acquaintances should be asked to bring the actual products to the hospital for analysis.

Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate.

There has been a resurgence in the use of 2,4-dinitrophenol, C6H4N2O5 (DNP) recently as an illegal weight loss drug. We present a case of a healthy 25-year-old girl who took two tablets of DNP, purchased from an overseas online retailer. She was managed with aggressive, invasive cooling measures and 2.5 mg kg-1 dantrolene. Despite this, her temperature continued to rise exponentially to 41.5°C. Cardiac arrest occurred and resuscitation was unsuccessful. To our knowledge, this is the first reported case of the ineffective use of dantrolene in acute DNP poisoning. We review the pathophysiology of DNP toxicity and argue that the use of dantrolene therapy is biochemically implausible, based on poor evidence and likely to be futile. We have contacted the UK National Poisons Information Service (NPIS/TOXBASE) to propose changes to the management of acute DNP toxicity.

Death within 44 days of 2,4-dinitrophenol intake.

We report the case of a 50-year-old obese man (115 kg body mass at 1.77 m height), who started taking 2,4-dinitrophenol (DNP) for weight reduction 44 days before his death. After 43 days of taking DNP, the man showed signs of intoxication with nausea, vomiting, and attacks of sweating. After admission to a hospital where the man concealed his DNP intake, sinus tachycardia, tachypnea, and general unrest were noted. The patient died 9 h after the onset of those symptoms. Upon autopsy, a yellowing of palms and soles was striking. The initially uncertain cause of death could only be clarified by the forensic toxicological examinations and subsequent police investigations. Finally, the man had a total intake of 12.3 g of DNP in 44 days which is relatively high compared to other lethal DNP intoxications.

Beware the yellow slimming pill: fatal 2,4-dinitrophenol overdose.

An industrial chemical, 2,4-dinitrophenol (DNP), has found use as a weight loss drug. It is extremely toxic in overdose and has a narrow therapeutic window with significant interindividual variability in metabolism. The rise in internet-based sales and distribution of this drug has seen an increased incidence of both accidental and intentional overdose presenting to emergency departments across the UK. No antidote currently exists and overdose is often fatal despite management based on current recommendations. We report a case of intentional overdose of DNP in a young man and discuss the current treatment guidelines. The case highlights the need for an increased awareness among frontline medical staff of the effects of DNP poisoning and questions the need for a more aggressive approach in the management of acute toxicity.

The Role of Adverse Event Reporting in the FDA Response to a Multistate Outbreak of Liver Disease Associated with a Dietary Supplement.

OBJECTIVE: Liver disease is a potential complication from using dietary supplements. This study investigated an outbreak of non-viral liver disease associated with the use of OxyELITE Pro(TM), a dietary supplement used for weight loss and/or muscle building. METHODS: Illness details were ascertained from MedWatch reports submitted to the U.S. Food and Drug Administration (FDA) describing consumers who ingested OxyELITE Pro alone or in combination with other dietary supplements. FDA's Forensic Chemistry Center analyzed samples of OxyELITE Pro. RESULTS: From February 2012 to February 2014, FDA received 114 reports of adverse events of all kinds involving consumers who ingested OxyELITE Pro. The onset of illness for the first report was December 2010 and for the last report was January 2014. Thirty-three states, two foreign nations, and Puerto Rico submitted reports. Fifty-five of the reports (48%) described liver disease in the absence of viral infection, gallbladder disease, autoimmune disease, or other known causes of liver damage. A total of 33 (60%) of these patients were hospitalized, and three underwent liver transplantation. In early 2013, OxyELITE Pro products entered the market with a formulation distinct from products sold previously. The new formulation replaced 1,3-dimethylamylamine with aegeline. However, the manufacturer failed to submit to FDA a required "new dietary ingredient" notice for the use of aegeline in OxyELITE Pro products. Laboratory analysis identified no drugs, poisons, pharmaceuticals, toxic metals, usnic acid, N-Nitroso-fenfluramine, pyrrolizidine alkaloids, aristocholic acid, or phenethylamines in the products. CONCLUSIONS: Vigilant surveillance is required for adverse events linked to the use of dietary supplements.

[Fatal course following poisoning with an illegal weight-reducing agent]. / Fatalt forløb efter forgiftning med illegalt slankemiddell.

DNP is a weight-reducing agent, which has been revived through sale over the Internet. DNP uncouples the oxidative phosphorylation in cells, leading to an excessive production of heat. A 39-year-old male ingested four grams of DNP and developed severe muscular stiffness and eventually cardiac arrest. Intubation was unsuccessful, and tracheotomy was performed on scene. Ventilation proved impossible, and the patient was declared dead in the pre-hospital setting. Doctors need to recognize potential lethal intoxications. Symptomatic treatment is warranted.

Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

Clenbuterol toxicity: a NSW poisons information centre experience.

OBJECTIVE: To describe the epidemiology and toxicity of clenbuterol in exposures reported to the NSW Poisons Information Centre (NSWPIC). DESIGN AND SETTING: Retrospective observational study analysing data from all calls about clenbuterol exposure recorded in the NSWPIC database from 1 January 2004 to 31 December 2012. The NSWPIC coversthe Australian jurisdictions New South Wales, Tasmania and the Australian Capital Territory 24 hours a day and provides after-hours cover for the rest of Australia for 7 nights each fortnight. MAIN OUTCOME MEASURES: Total number of exposures, source of call (hospital, health care worker, member of the public), time from exposure to call, reasons for drug use, clinical features and advice given. RESULTS: Callers reported 63 exposures to clenbuterol, with a dramatic increase from three in 2008 to 27 in 2012. Of the 63 calls, 35 were from hospital, two from paramedics, one from general practice and 21 direct from the public. At least 53 patients (84%) required hospitalisation. The commonest reasons for use were bodybuilding and slimming. The most common features were tachycardia (24 patients), gastrointestinal disturbance (16) and tremor (11). Exposure was also associated with cardiotoxicity including one cardiac arrest in a 21-year-old man. CONCLUSION: Although a well recognised doping issue among elite athletes, clenbuterol use has spread out into the general public, especially during 2012, and should be considered in patients using bodybuilding or slimming products who present with protracted sympathomimetic features. The potential for misuse of this substance requires reconsideration of its current poison schedule registration and its availability.

[Acute poisoning with weight-loss dietary supplement falsely suggesting the use of amphetamine]. / Ostre zatrucie suplementem diety wspomagajacym odchudzanie falszywie sugerujace uzycie amfetaminy.

OBJECTIVE: We report a case of abuse of weight-loss dietary supplement in 27-year-old man, with characteristic for amphetamine sympathomimetic symptoms and positive analysis of this drug in the urine by immunoassay method (FPIA; Axsym, Abbott). However positive result was not confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). CASE REPORT: The patient ate nine tablets of the Thermal Pro with declared composition of caffeine (250 mg), bitter orange (200 mg), beta-phenylethylamine (100 mg), willow bark (75 mg), Cayenne pepper (40 mg), 1,3-dimethyloamyloamine (DMAA, 35 mg), gooseberry extract (20 mg), bergamot orange (20 mg), black pepper (5 mg), after two-month period of regular consumption at dose of 2-3 capsules per day. After 4 hours, during admission to the Department of Toxicology, patient manifested typical sympathomimetic symptoms: anxiety, agitation, pale skin, sweats, tachycardia 120/min, mydriasis. Following the outcome of detecting amphetamine/methamphetamine in the patient's urine at 2377 ng/mL concentration using FPIA method, drug intoxication was suspected. It was considered that the ingestion was intentional or unconscious of adulterated dietary supplement. In view of the strong opposition of the patient, who denied any use of psychoactive substances, it was decided to re-examine collected speciments. The liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) method did not confirm the presence of amphetamine in the patient's blood and urine. Based on the composition of dietary supplements for substances which could be responsible for the positive amphetamine result in urine by FPIA method and available literature data, it was concluded that the substances that may react in the immunoassay could be dimethylamyloamine (DMAA, geranamine) or bitter orange components. CONCLUSION: False positive urinalysis towards amphetamine/methamphetamine by immunoassay and presence of sympathomimetic effects may contribute to a false diagnosis of this drug poisoning. Definitive confirmation of such intoxication requires the use of the reference methods.

Serotonin syndrome following overdose of a non-prescription slimming product containing sibutramine: a case report.

INTRODUCTION: Non-prescription slimming products are popular and can be easily purchased from the Internet. However, adulteration of these products with undeclared substances including prescription drugs is not uncommon. We report a case of serotonin syndrome after an overdose of a non-prescription product containing sibutramine. CASE REPORT: A 21-year-old woman presented with somnolence, sinus tachycardia, generalised increase in tone, hyper-reflexia and clonus more prominent in the lower limbs after an intentional overdose of a non-prescription slimming product obtained from the Internet. The product was later found to contain sibutramine and other substances such as animal thyroid tissues, caffeine and phenolphthalein. Quantitative analysis of patient's serum on presentation revealed a sibutramine concentration of 112 ng/mL, which far exceeded the reported peak serum concentration after a single oral dose of 15 mg (the maximum daily recommended dose). No other culpable agent was identified. The overall clinical presentation was compatible with serotonin syndrome associated with sibutramine overdose. The patient made a full recovery after supportive management. DISCUSSION AND CONCLUSION: This case highlighted the health threat posed by non-prescription slimming products sold over the Internet. Sibutramine overdose can result in serotonin syndrome, as in overdose of other serotonergic agents. Early recognition and timely supportive treatment are essential to ensure a good clinical outcome.

2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death.

2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.

Case series on a diversity of illicit weight-reducing agents: from the well known to the unexpected.

AIMS: To provide an overview of illicit weight-reducing agents found in over-the-counter slimming products ingested by poisoned patients. METHODS: The clinical details and analytical findings of slimming products involved in poisoning cases between 2004 and 2009 were reviewed. RESULTS: Sixty-six (including one fatal) poisoning cases were encountered. Eighty-one products were analysed and found to contain undeclared prescription weight-loss drugs, drug analogues, banned drugs, drugs used for an inappropriate indication or animal thyroid tissue, with up to six illicit agents within the same product. Many products were readily available from shops or the Internet. CONCLUSIONS: A rich diversity of illicit, potentially harmful weight-reducing agents was found in over-the-counter slimming products.

Deliberate poisoning with dinitrophenol (DNP): an unlicensed weight loss pill.

A 46-year-old man took a lethal dose of an agent called dinitrophenol (DNP). He presented 11 h after ingestion with loin pain, diarrhoea and vomiting. He rapidly deteriorated with profound hyperthermia, acute renal failure, hyperkalaemia, metabolic acidosis and eventually haemodynamic instability. Despite aggressive supportive measures and rapid sequence induction, he deteriorated and died 21 h after ingestion. DNP is a metabolic poison that acts by uncoupling oxidative phosphorylation, leading to uncontrolled hyperthermia. It is an illegal weight loss agent that is used by body builders and is freely available on many internet websites. This case highlights the potential for patients to obtain and ingest exotic poisons. A summary of currently recommended treatment and a review of the literature on DNP is included, as well as a discussion of therapies that may be effective in treating hyperthermia in this situation.