An outbreak of severe coagulopathy from synthetic cannabinoids tainted with Long-Acting anticoagulant rodenticides

Devgun, Jason; Rasin, Arkady; Kim, Theresa; Mycyk, Mark B.; Bryant, Sean M.; Wahl, Michael; DesLauriers, Carol; Navon, Livia; Moritz, Erin D.; Thompson, Trevonne M.; Swoboda, Henry; Lu, Jenny J.; Aks, Steven E.

doi:10.1080/15563650.2019.1690149

Cited by 23 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A lack of information about purity, mislabeling, pharmaceutical impurities, and hazardous cutting agents can pose a risk for drug users. A series of patients who presented to a hospital with coagulopathy and bleeding diathesis that were related to long-acting anticoagulant rodenticide adulterants of synthetic cannabinoids exemplifies their potentially fatal consequences (Devgun et al 2019;Kelkar et al 2018). Potentially severe drugdrug interactions are a risk when more than one substance is used, including prescription medications (Contrucci et al 2020;Inan et al 2020).…”

Section: Miscellaneous Risks Associated With Designer Drug Usementioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

View full text Add to dashboard Cite

Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

show abstract

Section: Miscellaneous Risks Associated With Designer Drug Usementioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

View full text Add to dashboard Cite

show abstract

“…It was unclear if the LAARs themselves underwent any substantial pyrolysis during smoking of the synthetic cannabinoids, or what the effective exposure dose was. A lack of easily obtainable quantitative LAARs concentrations in the blood of victims may have resulted in more outpatient coagulation testing and importantly, more costly, and lengthy oral vitamin K 1 supplementation than necessary [1][2][3]6]. To that end, the qualitative LC-MS/MS LAARs assay offered by NMS Labs [13] to treating physicians during the outbreak in Illinois can detect only brodifacoum in blood samples and is inefficient for monitoring poisoned patients over time as several tests would have been required until blood concentrations dropped to <10 ng/mL, the detection level of the assay [4][5][6]12,13].…”

Section: Discussionmentioning

confidence: 99%

“…The importance of real-time, quantitative toxicology data available for physicians treating poisoned patients was illustrated during the 2018 outbreak in Illinois of severe coagulopathy provoked by inhaled illicit synthetic cannabinoids products contaminated with commercially-available brodifacoum, difenacoum, and bromadiolone, three potent, long-acting anticoagulant rodenticides (LAARs) [1][2][3].…”

Section: The Clinical Challengementioning

confidence: 99%

“…However, at the present time, neither of the two reference laboratories provides testing for plasma concentrations of other potent LAARs such as difenacoum and bromadiolone. This deficiency represents a life-threatening, unmet medical need because difenacoum, bromadiolone and brodifacoum were detected in blood during the recent outbreak in Illinois and other States [1][2][3]. Hence, quantitative determination of difenacoum and bromadiolone, in addition to brodifacoum, in blood samples from patients hospitalized for suspected acute LAARs poisoning should be urgently made available to physicians.…”

Section: Unmet Clinical Laboratory Needmentioning

confidence: 99%

See 1 more Smart Citation

Unmet clinical laboratory need in patients hospitalized for acute poisoning from long-acting anticoagulant rodenticides

Breemen

Hafner

Nosal

et al. 2021

Toxicology Communications

View full text Add to dashboard Cite

the importance of real-time, quantitative toxicology data available for physicians treating poisoned patients was illustrated during the 2018 outbreak in illinois of severe coagulopathy caused by inhaling illicit synthetic cannabinoids products contaminated with commercially-available brodifacoum, difenacoum, and bromadiolone, three potent, long-acting anticoagulant rodenticides (laaRs). identification and quantification of these life-threatening toxins in blood samples of hospitalized patients required toxicology testing with liquid chromatography-tandem mass spectrometry (lc-Ms/Ms) that was not available in clinical laboratories of hospitals at the time of the outbreak. this highly-sensitive, quantitative assay can provide critical information to guide patient care during and after hospitalization, including identification of offending laaRs, estimates of the ingested dose, and dosage and discontinuation of oral vitamin K 1 therapy after hospital discharge once plasma laaRs concentrations decreased to a safe level (<10 ng/ml). accordingly, we propose an action plan to enable treating physicians to quantify plasma concentrations of several laaRs simultaneously in poisoned patients. it involves rapid (<15 min), sensitive, and validated lc-Ms/Ms methods developed, tested and validated in our laboratory. this will allow treating physicians to request quantitative plasma laaRs testing, report test results in the patient's hospital discharge summary, and recommend regular monitoring of plasma laaRs concentrations in the outpatient setting.

show abstract

“…A recent outbreak of long-acting anticoagulant rodenticide (LAAR)-associated coagulopathy and life-threatening bleeding in Illinois and several other States [1][2][3] focused attention on long-term treatment of this condition with vitamin K1 (VK 1 ). Current standard of care treatment of patients poisoned by the LAAR brodifacoum (BDF) is VK 1 given intravenously or orally, thereafter requiring supplementation for durations of weeks to months.…”

Section: Introductionmentioning

confidence: 99%

Brodifacoum pharmacokinetics in acute human poisoning: implications for estimating duration of vitamin K therapy

Nosal

Breemen

Haffner

et al. 2021

Toxicology Communications

View full text Add to dashboard Cite

Standard of care follow-up therapy for patients poisoned by long-acting anticoagulant rodenticides (LAARs) is daily high-dose (up to 100 mg per day) oral vitamin K1 (VK 1) for weeks to months to over a year. The availability of CLIA-certified quantitative testing for plasma LAAR concentrations can now assist health care providers in determining when to safely discontinue VK 1 therapy. We present estimates of treatment duration required to reach safe concentrations (< ¼10ng/ml) using serial measurements of plasma brodifacoum (BDF, a potent LAAR) concentrations obtained from patients poisoned after inhaling synthetic cannabinoids containing BDF. We fit the data to zero-order (linear) and first-order (exponential) curves, the latter to account for enterohepatic circulation of BDF. The results show that estimates of therapy duration are significantly longer when exponential clearance is assumed. Accordingly, we recommend that plasma BDF concentrations be monitored simultaneously with international normalization ratio (INR) during follow-up of poisoned patients, and that concentrations be determined after VK 1 therapy is discontinued to document persistence of safe concentrations.

show abstract

An outbreak of severe coagulopathy from synthetic cannabinoids tainted with Long-Acting anticoagulant rodenticides

Cited by 23 publications

References 27 publications

Designer drugs: mechanism of action and adverse effects

Designer drugs: mechanism of action and adverse effects

Unmet clinical laboratory need in patients hospitalized for acute poisoning from long-acting anticoagulant rodenticides

Brodifacoum pharmacokinetics in acute human poisoning: implications for estimating duration of vitamin K therapy

Contact Info

Product

Resources

About