Fatal Intoxication by the Novel Cathinone 4-Fluoro-3-methyl-α-PVP.

A 30 year old non-hispanic white male was found unresponsive at his workplace and admitted to the hospital in cardiac arrest. He was pronounced deceased shortly after arrival. At autopsy the pathologist noted a 176 pound, well-nourished, atraumatic, adult male with significant bilateral frothy pulmonary edema (right lung 930 g and left lung 1,130 g), cardiomegaly (430 g), dilated ventricles and slight cerebral edema. Upon completion of the systematic toxicological analysis scope for the Franklin County Coroner's Office Toxicology Laboratory, no known drugs were found. Further review of the gas chromatography--mass spectrometry (GC--MS) full-scan library summary reports showed an unknown peak in both the blood and urine solid phase extracts. An analogue of α-pyrrolidinovalerophenone (α-PVP) was identified, and a GC--MS selected ion monitoring method was developed to identify and quantitate the presence of 4-fluoro-3-methyl-α-PVP. This method quantified the drug at 26 ng/mL in gray top femoral blood, 30 ng/mL in purple top heart blood and 20 ng/mL in red top vitreous humor. Qualitative presence was also observed in the urine but was not detected in the liver. The decedent's cause of death was determined to be due to fluoro-methyl-PVP toxicity and the manner was ruled to be accidental. Investigational follow-up interviews corroborated drug use by the deceased with a preference of research chemicals and synthetic cannabinoids via the internet. No published literature is available currently, and to the author's knowledge this is the first incident of a fatal death solely attributed to this substituted cathinone.

Child Fatalities Due to Heroin/Fentanyl Exposure: What the Case History Missed.

This case report presents three unrelated children found to have heroin and/or fentanyl in their systems after general unknown systematic toxicological analysis (STA). The first case involves an 11-month-old male found unresponsive at their residence. The scene response suggested a potentially unsafe sleeping condition or a sudden unexplained infant death. The second case is a 14-month-old female found unresponsive after eating soft candies, suggesting that a choking related death may have occurred. The third case is a 12-year-old male found unresponsive in bed and foaming from the mouth. Gum was removed from the child's airway, suggesting another choking related death. The STA included a 14-drug category enzyme linked immunosorbant assay (ELISA) screening in whole blood. Cases 1 and 3 were presumptively positive for fentanyl, while Case 2 was presumptively positive for opiates and fentanyl. Reflex confirmation was performed in blood, urine and gastric contents, by solid-phase extraction (SPE) for 12 opiates including morphine and 6-monoacetylmorphine (6MAM) by gas chromatography-mass spectrometry (GC-MS) and for fentanyl, norfentanyl, and novel analogs, by liquid chromatography tandem mass spectrometry (LC-MS-MS). High concentrations of fentanyl and 6MAM in the gastric contents of Case 1, along with the presence of diacetylmorphine, suggested probable enteral ingestion of heroin and fentanyl, separately or in a combined formulation. Interpretation of the toxicology results could not determine a probable route of exposure to heroin/fentanyl in Case 2, however, the cause of death was clearly related to this drug mixture. In Case 3, the presence of acetylfentanyl suggested an illicit fentanyl exposure. The intention of this case report is to demonstrate the need for a STA approach for all non-trauma postmortem cases regardless of case circumstances, age or suspicion of drug use.

Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse?

BACKGROUND: There has been a significant spike in fentanyl-related deaths from illicit fentanyl supplied via the heroin trade. Past fentanyl access was primarily oral or dermal via prescription fentanyl patch diversion. One factor potentially driving this increase in fatalities is the change in route of administration. Rapid intravenous (IV) fentanyl can produce chest wall rigidity. We evaluated post-mortem fentanyl and norfentanyl concentrations in a recent surge of lethal fentanyl intoxications. METHODS: Fentanyl related deaths from the Franklin County coroner's office from January to September 2015 were identified. Presumptive positive fentanyl results were confirmed by quantitative analysis using liquid chromatography tandem mass spectrometry (LC/MS/MS) and were able to quantify fentanyl, norfentanyl, alfentanyl, and sufentanyl. RESULTS: 48 fentanyl deaths were identified. Mean fentanyl concentrations were 12.5 ng/ml, (range 0.5 ng/ml to >40 ng/ml). Mean norfentanyl concentrations were 1.9 ng/ml (range none detected to 8.3 ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1 ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22 ng/ml and 20 ng/ml) with no norfentanyl detected. DISCUSSION: The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity. An alternate explanation could be a dose-related rapid onset of respiratory arrest. Deaths occurred with low levels of fentanyl in the therapeutic range (1-2 ng/ml) in apparent non-naïve opiate abusers. Acute chest wall rigidity is a well-recognized complication in the medical community but unknown within the drug abuse community. The average abuser of illicit opioids may be unaware of the increasing fentanyl content of their illicit opioid purchase. CONCLUSION: In summary we believe sudden onset chest wall rigidity may be a significant and previously unreported factor leading to an increased mortality, from illicit IV fentanyl use. Fentanyl and norfentanyl ratios and concentrations suggest a more rapid onset of death given the finding of fentanyl without norfentanyl in many of the fatalities. Chest wall rigidity may help explain the cause of death in these instances, in contrast to the typical opioid-related overdose deaths. Intravenous heroin users should be educated regarding this potentially fatal complication given the increasingly common substitution and combination with heroin of fentanyl.

Markedly Elevated Carbamazepine-10,11-epoxide/Carbamazepine Ratio in a Fatal Carbamazepine Ingestion.

Carbamazepine is a widely used anticonvulsant. Its metabolite, carbamazepine-10,11-epoxide, has been found to display similar anticonvulsant and neurotoxic properties. While the ratio of parent to metabolite concentration varies significantly, at therapeutic doses the epoxide concentration is generally about 20% of the parent. We report a case of fatal carbamazepine overdose in which the epoxide metabolite concentration was found to be 450% higher than the parent compound, suggesting a potential role for metabolite quantification in severe toxicity.

A fatal intoxication of 2,5-dimethoxy-4-chloroamphetamine: a case report.

Designer drugs appear to be increasing in popularity because of the ease of obtaining these constituents, the lack of ability to identify the substance(s) in routine drug screening, the appeal of the drug(s) being 'safe' due to them being marketed as a 'legal high' and possibly due to stronger restrictions that are being placed on prescription drugs. As components of designer drugs are identified and regulated by the DEA, new constituents, or analogs, of these designer drugs are being manufactured to circumvent legislation. 2,5-Dimethoxy-4-chloroamphetamine (DOC) is a substituted alpha-methylated phenethylamine and acts as a selective serotonin receptor partial agonist. There is limited literature on this particular compound and no literature that attributes death to use of this drug alone. We present a case of a 37-year-old male found at home lying face down next to a book titled 'Psychedelic Chemistry' by Michael Valentine Smith and in the early stages of decomposition. The decedent was a known methamphetamine abuser. A peripheral blood sample collected at autopsy was sent to toxicology for routine analysis. Results yielded negative for the drugs of abuse classes on the enzyme-linked immunosorbent assay screen but was positive for DOC during routine GC-MS analysis. A urine sample collected at autopsy was subjected to a routine urine liquid/liquid analysis via GC-MS, and the specimen was positive for DOC. Quantification analyses showed DOC concentration levels to be 377 ng/mL in iliac blood; 3,193 ng/mL in urine; 3,143 ng/g in liver and 683 ng/g in brain. DOC was not detected in the gastric contents. Caffeine was the only other compound detected in blood and urine. Due to the lack of literature, we believe that this is the first case where death can be attributed to DOC alone.

Acute exposure to a sublethal dose of imidacloprid and coumaphos enhances olfactory learning and memory in the honeybee Apis mellifera.

The decline of honeybees and other pollinating insects is a current cause for concern. A major factor implicated in their decline is exposure to agricultural chemicals, in particular the neonicotinoid insecticides such as imidacloprid. Honeybees are also subjected to additional chemical exposure when beekeepers treat hives with acaricides to combat the mite Varroa destructor. Here, we assess the effects of acute sublethal doses of the neonicotinoid imidacloprid, and the organophosphate acaricide coumaphos, on honey bee learning and memory. Imidacloprid had little effect on performance in a six-trial olfactory conditioning assay, while coumaphos caused a modest impairment. We report a surprising lack of additive adverse effects when both compounds were administered simultaneously, which instead produced a modest improvement in learning and memory.

A comparison of methadone, oxycodone, and hydrocodone related deaths in Northeast Ohio.

Increases in methadone and oxycodone related deaths have been recently documented in the United States. In response to these reports, the authors investigated cases over a six-year period in which postmortem toxicological analyses revealed the presence of methadone, hydrocodone, and oxycodone. The study was designed to determine whether regional methadone-associated mortality in Cuyahoga County reflected national trends and more specifically, to distinguish methadone mortality from other commonly used opioid analgesics. All records of decedents that were found to be positive for methadone, hydrocodone, and/or oxycodone in 1998-2003 were reviewed. The cause and manner of death and demographic information was compiled. The cases were divided into lethal intoxications and cases where a positive result was determined to be an incidental finding. Lethal intoxications as a result of only methadone, hydrocodone, or oxycodone were separated from polydrug intoxications. Thoroughout the study, an increase was observed in the number of positive cases. In contrast to recent national data, although the number of methadone-positive cases increased from 4 in 1998 to 18 in 2003, this did not result in an increase in methadone overdoses [1 death in 1998 (25%) to 4 deaths in 2003 (22%)]. Although the pharmacokinetic profiles differ, methadone, hydrocodone, and oxycodone lethal intoxications equally comprised 28-29% of cases in which these drugs were detected. There was an overlap in the range of blood concentrations observed for the drug-related death groups and the incidental finding groups. However, mean and median concentrations in oxycodone and hydrocodone related deaths were more than two times greater than those in non-drug-related deaths.