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Rodenticides
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
The warfarins (the carbon-3-substituted 4-hydroxycoumarin derivatives) and “superwarfarins” (brodifacoum, indanediones) (Figure 30.1) are popular rodenticides, whose properties were originally isolated from the sweet clover plant.† By 1950, the warfarins had achieved international notoriety as the most useful rodenticides. The clinical feasibility of oral anticoagulants in humans became known soon after with the realization of their relatively low toxicity. Rodent resistance to warfarin, however, became prevalent in the 1960s via autosomal dominant gene transmittance. By the 1970s, novel second-generation, very long-acting anticoagulants (superwarfarins) were synthesized to combat rodent resistance. Structures of 4-hydroxycoumarin (parent molecule), brodifacoum (long-acting coumarin derivative, with the parent molecule in blue), and 1,2-indandione.
Drug-induced alveolar haemorrhage
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Abigail R Lara, Marvin I Schwarz
Excess anticoagulation during warfarin or heparin therapy, or poisoning with superwarfarin rotenticides, may cause DAH in which the only clinical findings are dyspnoea, unexplained anaemia and evolving pulmonary infiltrates.21 Drug-induced thrombocytopenia has also been implicated as a causative factor in the development of DAH.22,23
Pregnancy outcomes after suicide attempts by self-poisoning and drug overdose: experience of a clinical pharmacology consultation service in Izmir, Turkey
Published in Journal of Obstetrics and Gynaecology, 2018
Although some agents can cause bleeding and pregnancy complications, the drugs taken for suicide attempts do not seem to be harmful to the human foetus. In our survey, two pregnant women experienced vaginal bleeding after taking ergotamine or rodenticide. The pregnancy with a high dose of ergotamine exposure resulted in a spontaneous abortion, but the other pregnancies resulted in healthy live births. Ergotamine poisoning can promote uterine contractions, and hence may cause foetal harm or abortion. Ergot alkaloids are contraindicated in all trimesters, but there are no conclusive data of an increased risk of birth defects. Brodifacoum and other superwarfarin rodenticides may also lead to fatal or nonfatal bleeding from any tissue or organ. Single cases resulting in a healthy birth, stillbirth, maternal and neonatal coagulopathy have been described following a rodenticide exposure during pregnancy. Our case of a woman who took brodifacoum at 12 weeks of gestation resulted in a maternal coagulopathy recovered completely. At week 39 of gestation, she delivered a healthy baby weighing 3400 g, measuring 50.1 cm in length (both 50th to 75th percentile).
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].
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
In 2018, more than 300 patients presented across the United States (mainly in Illinois) with severe coagulopathy and bleeding after using synthetic cannabinoids adulterated with potent synthetic coumarin anticoagulants (“superwarfarins”), and at least seven died [7–9]. The reason for adding long-acting coumarins to illicit drugs has not been elucidated [9]. An outbreak of a similar coagulopathy among users of synthetic cannabinoids occurred in Israel during 2021–2022 and was eventually traced to the adulteration of synthetic cannabinoids with the potent coumarin brodifacoum.