VPT 421: Veterinary Toxicology (2+0)

CHELATING AGENTS

• Chelating agents
  • Chelating agents are used in the treatment of poisoning with heavy metals. They incorporate the metal ion into an inner ring structure in the molecule by means of chemical groups called ligands (Greek word chele = claw, Latin word ligare = to bind).
  • The ligand donates electrons to the metal to form co-ordinate bonds.
  • It is the strength of these bonds, which render the chelated metal non-bioavailable and hence inactive.
  • After incorporating the metal, these agents form stable, biologically inert complexes that are excreted in urine.
• British Anti-Lewisite (BAL) or Dimercaprol
  • This chelating agent was developed as an antidote for arsenical gas lewisite during 1939-45 war.
  • Arsenic and other metal ions are toxic in relatively low concentrations because they combine with the – SH groups of essential enzymes, thus inactivating them.
  • Dimercaprol provides –SH groups, which combine with the metal ions to from relatively harmless ring compounds, which are excreted mainly in the urine.
  • As dimercaprol itself, is oxidized in the body and readily excreted, repeated administration is necessary to ensure that excess is available until all the metal has been eliminated.
  • Adverse effects are common, particularly with larger doses and include nausea and vomiting, lacrimation and salivation, paresthesia, muscular aches and pain, urticarial rashes, tachycardia and a raised blood pressure.
  • Gross over dosage may cause over breathing, muscular tremors, convulsions and coma.
  • BAL is far from an ideal antidote as it is rapidly inactivated, irritant and unstable.
  • Its intravenous administration may cause excitement, tremors and convulsions. It may be administered at a dose of 2-3 mg/kg by intramuscular injection but the total quantity administered depends on the amount of arsenic that is to be removed.
• DMSA (Mesodimercaptosuccinic acid)
  • It is probably the preferred chelator as it is much safer than BAL. It may induce a sulfur odor to the breath and urine.
• Unithiol (DMPS – Dimercapto propane sulphonate)
  • It is analogue of BAL with reduced toxicity and high water solubility. This agent effectively chelates lead and mercury.
  • It is well tolerated. It has also been shown to increase the rates of urinary excretion of antimony, cobalt, silver in poisoning cases in man.
• Sodium calcium edetate
  • It is the calcium chelate of the disodium salt of ethylene diamine-tetra-acetic acid.
  • Its effectiveness is due to its capacity to exchange calcium for lead in lead poisoning.
  • The lead chelate is excreted in urine, leaving behind calcium.
  • Dimercaprol may be combined with sodium calcium edentate when lead poisoning is severe e.g., with encephalopathy.
  • Adverse effects are fairly common and include hypotension, lacrimation, nasal stuffiness, sneezing, muscle pain and chills.Renal damage can also occur.
  • Dosage suggested for all species is 75 mg/kg. This may be given as a 2% solution by intravenous route as drips daily for three days followed by an interval of 3-5 days and then a further three days course.
• Dicobalt edetate
  • Cobalt forms stable non-toxic complexes with cyanide. It is toxic by itself especially when a wrong diagnosis is made.
  • Toxicity due to dicobalt edetate can be treated with sodium calcium edetate and intravenous glucose.
• Penicillamine ( Dimethylcysteine )
  • It is a metabolite of penicillin that contains –SH groups; it may be used to chelate lead and also copper.
• Desferrioxamine
  • It is product isolated from Streptomyces pilosus.
  • When desferrioxamine comes into contact with ferric iron, it forms a non-toxic complex of great stability. This complex s excreted in urine giving it a reddish colour and also in faeces.
  • It is not absorbed from the gut and has to be injected.
  • It has negligible affinity for other metals in the presence of iron.
  • When given by mouth it forms complex with iron in the lumen and prevents further absorption.