Chelation therapy/chelating agents

Palmer 1989 Robinson et al.1983). However, the ratio was almost certainly affected by initial chelation with Ca-DPTA, followed by daily intravenous therapy with the chelating agent, Zn-DPTA, treatments that would have increased the urinary excretion of americium (Breitenstein and Palmer 1989). The above not withstanding, the observations made on this subject demonstrate that fecal excretion was an important pathway of excretion in this subject long after mechanical clearance of americium from the respiratory tract would have been complete. This is consistent with observations made in nonhuman primates that show that americium is excreted into bile (see Section 3.4.4.4). However, the extent to which the biliary excretion pathway in humans might resemble that of nonhuman primates is not known. 

Domingo, J.L. (2006) Aluminium and other metals in Alzheimer s disease a review of potential therapy with chelating agents. J. Alzheimer Dis., 10, 331-341. 

Acetate not recommended for initial therapy of symptomatic Wilson s disease (should be treated initially with chelating agents)... 

For patients who are unable to tolerate penicillamine, trientine, another chelating agent, may be used in a daily dose of 1-1.5 g. Trientine appears to have few adverse effects other than mild anemia due to iron deficiency in a few patients. Zinc acetate administered orally increases the fecal excretion of copper and is sometimes used for maintenance therapy. The dose is 50 mg three times a day. Zinc sulfate (200 mg/d orally) has also been used to decrease copper absorption. Zinc blocks copper absorption from the gastrointestinal tract by induction of intestinal cell metallothionein. Its main advantage is its low toxicity compared with that of other anticopper agents, although it may cause gastric irritation when introduced. 

In this way, by reducing permeability barriers, combination therapy with antibiotic and chelating agent may enhance significantly the efficacy of suitable antibiotics in the topical treatment of local infection. 

Penicillamine (Cuprimine), a derivative of penicillin, is officially classified as a chelating agent that is often used in the treatment of heavy metal intoxication (e.g., lead poisoning). In addition, this drug has been used in patients with severe rheumatoid arthritis, and seems to be as effective as other DMARDs such as methotrexate, sulfasalazine, and gold therapy.68 98 Penicillamine, however, tends to be substantially more toxic than other DMARDs, and is therefore used rarely in the treatment of specific patients with rheumatoid arthritis.68... 

As these chelating agents became available 25-30 years ago they were met with an acclaim which was perhaps over enthusiastic. HEDTA as a decorporation agent of iron is inferior to DFOA and a recommendation that TTHA be used as an orally-acting therapy for the transuranics has never become practice. 

The main dose-limiting toxicity of all anthracyclines is myelosuppression, with neutropenia more commonly observed than thrombocytopenia. In some cases, mucositis is dose-limiting. Two forms of cardiotoxicity are observed. The acute form occurs within the first 2-3 days and presents as arrhythmias or conduction abnormalities, other electrocardiographic changes, pericarditis, and myocarditis. This form is usually transient and is asymptomatic in most cases. The chronic form results in a dose-dependent, dilated cardiomyopathy associated with heart failure. The chronic cardiac toxicity appears to result from increased production of free radicals within the myocardium. This effect is rarely seen at total doxorubicin dosages below 500-550 mg/m2. Use of lower weekly doses or continuous infusions of doxorubicin appear to reduce the incidence of cardiac toxicity. In addition, treatment with the iron-chelating agent dexrazoxane (ICRF-187) is currently approved to prevent or reduce anthracycline-induced cardiotoxicity in women with metastatic breast cancer who have received a total cumulative dose of doxorubicin of 300 mg/m2. All anthracyclines can produce "radiation recall reaction," with erythema and desquamation of the skin observed at sites of prior radiation therapy. 

Sodium Aurothiomalate The treatment of adverse effects is symptomatic. Therapy is withdrawn and a chelating agent such as dimercaprol may be used. 

Curnov A,McIlroy BW, Postle-Hacon MJ, Porter JB,MacRobert AJ,Bown SG. Enhancement of 5-aminolaevulinic acid induced photodynamic therapy using hydroxypyridi-none iron chelating agents. Br J Cancer 1998 78 1278. 

A Note about Chelation Therapies. Chelation therapies are used to prevent or treat metal-induced toxicities. They are often used in acute poisoning scenarios, but can also be used to assess exposure. One of the major challenges in the management of chelation therapies is the tendency for chelating agents to interact with essential metals, particularly calcium and zinc. Chelation therapies should only be administered by a physician due to the potential to disrupt essential metal functions. The Food and Drug Administration does not regulate dietary supplements, and several do it yourself chelation therapies are available. These are not advisable. 

Treatment While damage cannot be cured, disease progression can be slowed down by lifelong chelation therapy. These chelating agents (including d-penicillamine or trientine hydrochloride) can help remove copper from tissue, and zinc supplements may help slow copper absorption, but patients also need to follow a diet low in copper. In extreme conditions where patients do not respond to treatment, liver transplantation may be an option. 

Excess transition metals can be removed by chelation therapy using chelating agents such as deferoxamine, EDTA or D-penicillamine, and supplements can be used in cases of deficiency (e.g. iron(II) suphate or zinc(II) sulfate). 

The treatment of thalassemia, as in other metal overload disorder, is chelation therapy. The chelating agent most widely nsed is deferoxamine administered subcutaneously. The search for an orally administered iron chelator has intensified in recent years, leading to cUnical trials of many potential new iron chelators snch as deferiprone(Ll). However, many issues regarding the nse of these drugs, such as dose-related toxicity and recommended age of initiation, remain unresolved. " ... 

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