General Principles of Metal Toxicity
2) They may directly damage tissue (direct irritation) by mechanisms described previously.
Typically, children and the elderly are more prone to toxic responses to metals than young and middle-aged adults. Also, the life-style of the individual may influence their response to metal toxicity (smokers are at much greater risk of cadmium toxicity, since cadmium may be found in cigarette smoke).
Treatment of Metal Toxicity -- Chelation Therapy -- In addition to supportive and symptomatic treatment, the primary goal of metal toxicity is to decrease the risk of toxic damage by the metal. This is best accomplished by hastening the excretion of the metal. The therapeutic approach to increase excretion of metals is through the use of chelating agents that bind to the metal, effectively inactiving it and allowing its excretion.
DMPS -- 2,3 dimercapto-1-propane sulphonic acid -- This is a water soluble version of BAL and may be administered orally. It may be used in mercury, methylmercury, cadmium, copper, nickel, and arsenic poisoning.
EDTA -- ethylenediaminetetra-acetic acid -- This chelator is most often given as the calcium salt (to reduce the incidence of side effects and to increase solubility). This dosage form makes it especially useful for the treatment of lead toxicity. In chronic lead toxicity there is a state of hypocalcæmia. Lead has a greater affinity for EDTA than calcium does, so the calcium is displaced and the lead bound to EDTA and excreted. This also helps to restore the body load of calcium.
Penicillamine -- This drug is a metabolite of the antibiotic penicillin (is has no clinically relevant anti-bacterial actions). It was initially used in the treatment of Wilson's disease, which is characterised by a state of hypercupræmia (excess copper levels). It chelates and removes copper, lead, mercury, and iron.
DTPA -- diethylenetriaminepenta-acetic acid -- Is used primarily in the treatment of cadmium toxicity (as an adjunct to BAL therapy).
Desferrioxamine -- Binds to iron and is used primarily in cases of iron overload.
DDC -- diethyldithiocarbamate, dithiocarb -- Is used primarily for nickel carbonyl toxicity.
Chronic Arsenic Toxicity -- Has numerous organ effects
inhalation causes a metallic taste, shortness of breath, chest pain, and cough with a bloody or foamy sputum
ingestion -- nephrotoxicity (Cadmium bound to metallothionein is filtered through the glomerulus for excretion. However, it may be reabsorbed and once in the tubular epithelium may cause direct irritation and cell damage, resulting in necrosis and tubular occlusion as described in the renal toxicity section. Thus, metallothionein, by presenting the kidney with cadmium, may contribute to its nephrotoxicity.), testicular toxicity, calcium displacement from bones (This causes osteoporosis and the bones may become brittle and can be quite painful. Cases of chronic cadmium ingestion of contaminated fish and rice in Japan gave rise to an epidemic of cadmium toxicity called itai-itai disease (ouch-ouch disease) because of the pain experienced by affected individuals. NOTE that chelation therapy is relatively ineffective in chronic cadmium toxicity. Once the cadmium has been bound to metallothionein, chelators have little effect in hastening excretion (the affinity of cadmium for metallothionein is greater that than for the chelating agent). Chelators are effective in acute cadmium toxicity (before complexation with metallothionein has occurred).
Chronic toxicity -- may be divided into three distinct phases, dependent upon how chronic the exposure is
middle -- intermittent vomiting, incoordination, vague pain in extremities and joints, paræsthesias, paralysis of extensor muscles (foot and wrist drop), menstrual irregularities, abortion
late -- persistent vomiting, ataxia, stupor, lethargy, encephalopathy, hypertension, papilldema, cranial nerve paralysis, delirium, convulsions, coma, decreased bone density
The progression of chronic toxicity begins with mild gastric disturbances and continues to present as more severe gastric damage and progressive nerve damage, ultimately causing mental impairment that may often be mis-diagnosed as learning disorders in children.
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