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Cardiovascular drugs
Published in Bev-Lorraine True, Robert H. Dreisbach, Dreisbach’s HANDBOOK of POISONING, 2001
Bev-Lorraine True, Robert H. Dreisbach
The various anticoagulant drugs are used medically to inhibit the clotting mechanism. Warfarin and a number of chemicals with similar action are also used as rodenticides: dicumarol (bishydroxycoumarin), difenacoum, chlorophacinone, bromadiolone, brodifacoum (Talon), coumatetryl (Racumin), coumachlor, diphacinone, and pindone.
An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum
Published in Clinical Toxicology, 2023
Yael Lurie, Yona Nadir, Ron Hoffman, Asaf Miller, Edna Efrati, Gil Ring, Dana Sonenfeld, Nitai Bar, Hisam Zaidani, Alexander Strizevsky, Mahdi Asali, Ophir Lavon, Daniel Kurnik
The simultaneous presentation of multiple young, otherwise mostly healthy users of illicit street drugs with an unexplained severe coagulopathy and bleeding was the key finding in a previous outbreak of long-acting anticoagulant rodenticide-associated coagulopathy in Illinois, USA, in 2018 [9,16,20–23], and those similarities allowed us to rapidly identify and respond to the outbreak. In both outbreaks, the patients were predominantly young men (73% males, median age 32 years in Illinois; 91% males, median age 38 years in Israel [9]) who reported synthetic cannabinoid use prior to admission (94% in our cohort). Moreover, in both outbreaks, brodifacoum was identified in all blood samples examined, while additional coumarin anticoagulants were present in Illinois (difenacoum in 33% of patients, bromadiolone in 13%, and warfarin in 7% [7]; difenacoum in 55%, bromadiolone in 5%) [9]. In our study, we determined plasma concentrations of brodifacoum and warfarin only and detected warfarin (in addition to brodifacoum) in one patient (4%).
Bromoxynil and 2-methyl-4-chlorophenoxyacetic acid (MCPA) poisoning could be a bad combination
Published in Clinical Toxicology, 2018
Betty S. H. Chan, Angela L. Chiew, Sarah Grainger, Colin B. Page, Alan Gault, Ahmed Mostafa, Michael S. Roberts, Nicholas A. Buckley, Geoffrey K. Isbister
From January 2010 to August 2016, there were 22 cases. 20 had ingested MCPA with other herbicides such as dicamba or bromoxynil. (Table 1). There were two fatal cases that reported just bromoxynil ingestion but both had detectable MCPA concentrations (Tables 1 and 2). Hence all 22 cases had ingested MCPA. Of these, eight had also taken dicamba or other herbicides and 14 had co-ingested bromoxynil (Table 1). This includes the two cases that Chiew et al. [1] reported. There were eight fatalities, seven were characterized by tachycardia, tachypnoea, hyperthermia, rising CO2 production, acidosis and sudden asystolic arrest. Death occurred between 12 and 30 hours post-ingestion. The median maximum temperature and partial pressure of CO2 were 39.3 °C (range: 37.9–43 °C) and 80 mmHg (range: 44–122 mmHg), respectively. Of the seven fatalities with this toxidrome, six had apparently taken bromoxynil with MCPA, with one of these also taking glyphosate and bromadiolone. Note this includes the two that did not report MCPA co-ingestion. There were two fatalities that were related to MCPA and dicamba or moxidectin co-ingestion (Tables 1 and 2). One patient had the same toxidrome and one died on day 7 from MCPA and moxidectin ingestion, after severe rhabdomyolysis and acute renal failure. Discrepancy between the laboratory assays and patients reports suggest that history may be inaccurate. It was important to be able to perform laboratory assays to ascertain the pesticides causing death.
Effects of vitamin K1 treatment on plasma concentrations of long-acting anticoagulant rodenticide enantiomers following inhalation of contaminated synthetic cannabinoids
Published in Clinical Toxicology, 2020
Douglas L Feinstein, Daniel G Nosal, Swetha Ramanathan, Jifang Zhou, Luying Chen, Ronald C Hershow, Richard B van Breemen, Erik Wright, John W Hafner, Israel Rubinstein
In March 2018, an acute outbreak of life-threatening synthetic cannabinoid (SC)-associated coagulopathy and bleeding was reported in 15 counties in Illinois, USA [1]. A total of 164 confirmed and probable cases, including five deaths, were linked to this outbreak. It was instigated by people inhaling SCs contaminated with commercially available, commonly used, lipophilic, long-acting anticoagulant rodenticides (LAARs; aka “superwarfarins”) brodifacoum (BDF), difenacoum (DiF), and bromadiolone (BDL) that are up to 100 times as potent as warfarin [2]. Detailed accounts of clinical and laboratory manifestations of the outbreak were recently published [3–5]. Upon admission to hospital, poisoned patients were treated with blood products and intravenous and oral vitamin K1 (VK1), and then discharged with high-dose VK1 for several months [3–6]. However, plasma concentrations of BDF, the most potent LAAR, or of DiF and BDL were not reported. Conceivably, that data could help guide decisions on whether to discontinue oral VK1 therapy even when International Normalized Ratio (INR) is reported as normal during follow-up [7]. In addition, BDF (as well as DiF) contains two chiral sites resulting in four isomers and two diastereomer pairs [8,9]. Although half-lives for BDF and Dif [8,10,11] enantiomers have been reported in animal studies, circulating half-lives of cis- and trans-isomers of BDF or other LAARs have not been reported in poisoned human subjects. Conceivably, the determination of relative BDF diastereoisomer concentrations in plasma of such patients could be valuable for the forensic investigation of outbreaks due to the extremely high stability of BDF, and therefore the ratio of cis-BDF to trans-BDF enantiomers does not change significantly from initial synthesis [12].