A recent multi-state outbreak of life-threatening bleeding following inhalation of synthetic cannabinoids has been attributed to contamination with the long-acting anticoagulant rodenticide (LAAR) brodifacoum, a second-generation, highly potent, long-acting derivative of the commonly used blood thinner warfarin. While long-term treatment with high-dose vitamin K1 restores coagulation, it does not affect brodifacoum metabolism or clearance, and, consequently, brodifacoum remains in the human body for several months, thereby predisposing to risk of bleeding recurrence and development of coagulation-independent injury in extrahepatic tissues and fetuses. This has prompted the evaluation of pharmacological measures that accelerate brodifacoum clearance from poisoned patients. Since the induction of certain cytochrome P450 (CYP) enzymes accelerates warfarin metabolism, using CYP inducers, such as phenobarbital, to accelerate brodifacoum clearance seems plausible. However, unlike warfarin, brodifacoum does not undergo significant metabolism in the liver, nor have the effects of phenobarbital on vitamin K1 metabolism been previously determined. In addition, the safety of phenobarbital in brodifacoum-poisoned patients has not been established. Therefore, we propose that CYP inducers should not be used to accelerate the clearance of brodifacoum from poisoned patients, but that alternative approaches such as reducing enterohepatic recirculation of brodifacoum, or using lipid emulsions to scavenge brodifacoum throughout the body, be considered.

中文翻译：

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是否应该使用细胞色素 P450 诱导剂来加速中毒患者体内布罗迪康的清除？

最近多州爆发了吸入合成大麻素后危及生命的出血事件，原因是长效抗凝灭鼠剂（LAAR）溴鼠灵污染，这是一种常用血液的第二代高效长效衍生物更薄的华法林。虽然长期使用大剂量维生素 K1 治疗可以恢复凝血功能，但它不会影响溴鼠灵的代谢或清除，因此，溴鼠灵会在人体内保留数月，从而容易出现出血复发和凝血非依赖性出血的风险。肝外组织和胎儿的损伤。这促使人们对加速溴鼠灵从中毒患者体内清除的药理学措施进行评估。由于某些细胞色素 P450 (CYP) 酶的诱导会加速华法林代谢，因此使用 CYP 诱导剂（例如苯巴比妥）来加速溴法康清除似乎是合理的。然而，与华法林不同的是，溴鼠灵在肝脏中不会进行显着的代谢，之前也没有确定苯巴比妥对维生素 K1 代谢的影响。此外，苯巴比妥在溴鼠灵中毒患者中的安全性尚未确定。因此，我们建议不应使用 CYP 诱导剂来加速中毒患者体内溴鼠灵的清除，但应考虑替代方法，例如减少溴鼠灵的肠肝再循环，或使用脂肪乳剂清除全身的溴鼠灵。