ANTIDOTES TO HEAVY METAL POISONING

大多数金属中毒对医生来说是一个巨大的挑战

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.