ANTIDOTES TO HEAVY METAL POISONING

大多数金属中毒对医生来说都是一个巨大的挑战 阿森纳的解药程序在过去的几个月里几乎没有变化 几十年。这项建议是一种基础广泛的金属解毒剂方法。 中毒是与消除金属的总体增加相适应的 从而降低中毒效应的发生率和严重程度。 我们采取了三管齐下的新方法，使用了两种有希望的药物，DMSA和 一硫醇。在一种方法中，历史悠久的方法使用络合剂 将在动物模型中进行研究，该模型将提供同时的动力学和 毒性数据。通过肠道途径排出的金属将会增加。 使用具有设计用于粘合的各种官能团的不可吸收树脂 胃肠道中的特定金属，并加速它们的消除。 被设计为在胆汁中快速排泄的特定螯合剂将是 单独使用或与树脂结合使用以增强金属 排泄物。最后，由于肾脏和肝脏功能可能在 金属中毒，或当金属的快速去除是关键的替代 利用体外络合血液透析途径加强 直接从血液中排出金属。选择一种特定的方法来 对特定金属的解毒是基于在 阐明金属的分布和排泄机制等 在中毒患者中使用这种特殊治疗方法的可能性 人类。

Most metal poisonings present a formidable challenge to the physician whose arsenal of antidotal procedures has changed little over the last several decades. This proposal is a broad based approach to antidotes for metal poisoning which is geared at the overall increase in elimination of the metal from the body thereby decreasing the incidence and severity of toxic effects. We have taken a three-pronged new approach using two promising agents, DMSA and unithiol. In one approach, the time honored approach use of complexing agents will be studied in animal models which will provide simultaneous kinetic and toxicity data. The excretion of metals by the enteric route will be enhanced using non-absorbable resins with a variety of functional groups designed to bind specific metals in the gastrointestinal tract and speed their elimination. Specific chelating agents designed to be rapidly excreted in the bile will be utilized both alone and in combination with the resins to enhance metal excretion. Finally, since renal and hepatic function may be compromised in metal intoxication, or when rapid removal of the metal is critical the alternate pathway of extracorporeal complexing hemodialysis will be utilized to enhance metal excretion directly from the blood. The choice of a particular approach to detoxification for a specific metal is based both on information gained in illucidating the mechanisms of distribution and excretion of the metal and on the probability of using that particular therapeutic approach in poisoned humans.