TNO Earth Environmental and Life Sciences, CBRN Protection, PO Box 45, 2280 AA Rijswijk, The Netherlands.
Chem Biol Interact. 2013 Mar 25;203(1):149-53. doi: 10.1016/j.cbi.2012.10.002. Epub 2012 Oct 16.
Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to improve treatment efficacy compared to a single injection treatment. Because of the effectiveness of continuous treatment, it was investigated to what extent a subchronic pretreatment with carbamate (pyridostigmine or physostigmine combined with either procyclidine or scopolamine) would protect against percutaneous VX exposure. Inclusion of scopolamine in the pretreatment prevented seizures in all animals, but none of the pretreatments affected survival time or the onset time of cholinergic signs. These results indicate that percutaneous poisoning with VX requires additional conventional treatment in addition to the current pretreatment regimen. Decontamination of VX-exposed skin is one of the most important countermeasures to mitigate the effects of the exposure. To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at different times in hairless guinea pigs percutaneously challenged with 4× LD50 VX in IPA. The results showed that RSDL decontamination at 15 min after exposure could not prevent progressive blood cholinesterase inhibition and therefore would still require additional treatment. A similar decontamination regimen with RSDL at 90 min showed that it still might effectively increase the time window of opportunity for treatment. In conclusion, the delay in absorption presents a window of opportunity for decontamination and treatment. The continuous release of VX from the skin presents a significant challenge for efficacious therapy, which should ideally consist of thorough decontamination and continuous treatment.
低挥发性有机磷神经毒剂，如 VX，很可能通过皮肤进入体内。肟类、阿托品和地西泮等药物的药代动力学与该药剂可变且持续的毒代动力学不匹配。与单次注射治疗相比，重复给予这些药物可提高治疗效果。由于连续治疗的有效性，研究了亚慢性预处理（氨基甲酸酯类[毒扁豆碱或依色林，联合苯环壬酯或东莨菪碱]）对经皮 VX 暴露的保护作用。预处理中包含东莨菪碱可防止所有动物发生癫痫发作，但没有一种预处理会影响存活时间或胆碱能体征的发作时间。这些结果表明，经皮 VX 中毒需要除目前的预处理方案外，还需要进行额外的常规治疗。VX 暴露皮肤的去污是减轻暴露影响的最重要对策之一。为了评估去污的时机窗口，用异丙醇中 4×LD50 VX 经皮挑战无毛豚鼠，测试了市售的皮肤去污剂 Reactive Skin Decontaminant Lotion（RSDL）在不同时间的去污效果。结果表明，暴露后 15 分钟进行 RSDL 去污不能预防血液胆碱酯酶的进行性抑制，因此仍需要额外的治疗。在 90 分钟时用 RSDL 进行类似的去污方案表明，它仍然可以有效地增加治疗的时机窗口。总之，吸收延迟为去污和治疗提供了时机窗口。从皮肤持续释放 VX 对有效的治疗提出了重大挑战，理想的治疗方法应包括彻底去污和持续治疗。
