Clinical Treatments for Common Metal Intoxications and Their Underlying Chemistry

Current Clinical Treatments for Common Metal Intoxications and Their Underlying Chemistry 

Lead intoxication is found in adults who have occupational or environmental exposures and produces a variety of symptoms involving the gastrointestinal tract (from oral exposures), the nervous system, the kidneys, and the blood (Cullen et al. 1983). It is also found in infants living in housing in which lead is present as residues from lead paint, plumbing, or the like (Needleman and Bellinger 1991). The principal sites at which the accumulation of lead gives rise to symptoms of chronic intoxication are the bone, the kidneys, and the brain and nervous system. Lead reacts with and inactivates three of the enzymes involved in the synthesis of heme to produce a characteristic 

The coordination preferences of lead include carboxylate oxygens, sulfhydryl sulfurs, and some other donor groups which can be used in combination with these. There are five chelating agents of possible use in the treatment of lead intoxication BAL, DMSA, DMPS, Na2CaEDTA, and D-penicillamine. The very limited availability of DMPS leaves the other four compounds available for use. 

Bauchner 1992). DMSA is given orally, is of very modest toxicity, induces a smaller urinary excretion of essential metals and a larger excretion of lead than Na2CaEDTA, and has been found to be superior to Na2CaEDTA in enhancing the excretion of lead in both animal and clinical studies. The log A stab for the PbDMSA complex is 17.4 (Harris et al. 1991), a somewhat smaller value than that reported for the PbEDTA complex, but DMSA can penetrate into some intracellular sites, possibly via transport systems for succinate. There is good reason to believe that it will soon become the preferred compound for the treatment of both acute and chronic lead intoxication. 

D-Penicillamine (DPA) is used in the treatment of lead intoxication as an oral medication which can be taken in the home (Glotzer and Bauchner 1992). The log A stab value for PbDPA complex is only 12.3 (Martell and Smith 1974), so this compound would be expected to be less effective than either Na2CaEDTA or DMSA, and this has been found to be the case in both animal and clinical studies. 

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