Monday, January 25, 2010

Therapeutic uses of Chelation Treatment; May have Gulf War Illness implications

 

 

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SOURCE:  Cheap Pharmacy Rx Blog

Drugs used to counteract drug overdosage are considered under the appropriate  headings,  e.g.,  physostigmine with atropine;  naloxone  with  opioids;  flumazenil  with  benzodiazepines;  antibody (Fab fragments) with digitalis; and N-acetyl-cysteine  with  acetaminophen intoxication. Chelating agents (A) serve as antidotes  in  poisoning with  heavy metals.

They act to complex and, thus, “inactivate”  heavy  metal  ions.  Chelates  (from Greek: chele = claw [of crayfish]) represent  complexes  between  a  metal  ion and molecules  that  carry  several binding  sites  for  the metal  ion.  Because  of their high affinity, chelating agents “attract” metal  ions present  in  the organism. The chelates are non-toxic, are excreted  predominantly  via  the  kidney, maintain  a  tight  organometallic  bond also in the concentrated, usually acidic, milieu  of  tubular  urine  and  thus  promote the elimination of metal ions.

Na2Ca-EDTA  is  used  to  treat  lead poisoning.  This  antidote  cannot  penetrate cell membranes and must be given parenterally. Because of its high binding affinity, the lead ion displaces Ca2+ from its bond. The lead-containing chelate is eliminated renally. Nephrotoxicity predominates among the unwanted effects.

Na3Ca-Pentetate is a complex of diethylenetriaminopentaacetic  acid  (DPTA) and serves as antidote in lead and other metal intoxications. Dimercaprol  (BAL, British Anti-Lewisite) was developed  in World War  II as an antidote against vesicant organic arsenicals (B). It  is able to chelate various metal  ions. Dimercaprol forms a  liquid,  rapidly  decomposing  substance that  is given  intramuscularly  in an oily vehicle.  A  related  compound,  both  in terms  of  structure  and  activity,  is  dimercaptopropanesulfonic acid, whose sodium salt is suitable for oral administration. Shivering,  fever, and  skin  reactions are potential adverse effects.  -

Deferoxamine  derives  from  the bacterium  Streptomyces  pilosus.  The substance  possesses  a  very  high  ironbinding capacity, but does not withdraw iron  from hemoglobin or  cytochromes. It is poorly absorbed enterally and must be given parenterally to cause increased excretion of iron. Oral administration is indicated  only  if  enteral  absorption  of iron is to be curtailed. Unwanted effects include  allergic  reactions.  It  should  be noted that blood  letting  is the most effective means of removing iron from the body;  however,  this method  is  unsuitable for treating conditions of iron overload associated with anemia.

D-penicillamine  can  promote  the elimination of  copper  (e.g.,  in Wilson’s disease) and of lead ions. It can be given orally. Two additional uses are cystinuria and rheumatoid arthritis. In the former,  formation of cystine stones  in  the urinary  tract  is  prevented  because  the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine  can  be  used  as  a  basal  regimen.  The  therapeutic  effect may result in part from a reaction with aldehydes,  whereby  polymerization  of collagen molecules into fibrils is inhibited.  Unwanted  effects  are:  cutaneous damage  (diminished  resistance  to mechanical stress with a tendency to form blisters),  nephrotoxicity,  bone marrow depression, and taste disturbances.

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