This document discusses chelating agents, which are drugs that bind to heavy metals in the body to facilitate their removal. Chelating agents have two or more electronegative groups that form stable bonds with metal cations. An ideal chelating agent has high affinity for metals, is water soluble, resistant to biotransformation, forms non-toxic complexes, and facilitates rapid excretion of the metal complex. Some commonly used chelating agents discussed are dimercaprol, DMSA, DMPS, EDTA, penicillamine, desferrioxamine, and deferiprone. The document outlines their mechanisms and uses for treating poisoning from metals like lead, mercury, arsenic, and iron.

1. ChelatingAgents
Dr. Ravi K. Sori

2. ‘’
Heavy Metal acts as general protoplasmic poison and impairs the
cell function
Have ability to form complexes with important biological radicals
like sulfhydryl hydroxyl, carboxyl, amino acid, imidazole
Exert toxic effects by combining with and inactivating
functional groups of enzyme
Lead
Mercury
Arsenic
Cadmium
Introduction
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3. ‘’ ➢ These are the drugs used to prevent heavy metal poisoning
Chelation: The process by which these organic compounds
combine with the metals to form relatively stable non ionised
ring complexes (chele - clow)
Introduction
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CHELATING AGENTS

4. ‘’ These compounds are usually flexible organic molecules which can
incorporate metal ions into their molecular structure by
means of chemical groups called ligands
Chele - Crab’s claw
Ligare - to bind
Introduction
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CHELATING AGENTS

5. ‘’ Have two or more electro negative groups that form stable
coordinate covalent bonds with the cationic metal atom
Chelator - metal complex is stable, biologically inert and excreted
in urine
Thus appropriate chelating agent can be effectively used in cases
of heavy metal poisoning
Introduction
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CHELATING AGENTS

6. ‘’
More affinity for metals than endogenous ligand
High solubility in water
Resistance to biotransformation
Form non toxic complexes with toxic metal
Accelerate mobilization and/or removal of the metals
Cheap and easy to administer
Easy excretion of chelating complex
Introduction
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Ideal Chelating Agent

7. ‘’
1. Dimercaprol (BAL)
2. Dimercaptosuccinic acid (DMSA)
3. Dimercaptopropane sulfonic acid (DMPS)
4. Disodium edetate (EDTA)
5. Calcium disodium edetate
6. Pencillamine
8. Desferrioxamine & Deferiprone
Introduction
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Chelating Agents used

8. ‘’Mechanism
ofaction
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Drug + Metallic ions
Non toxic
Water soluble complex
Eliminated by the
kidneys

9. 9
EDTA
Dimercaprol
Succimer
Penicillamine
Desferrioxamine
Deferiprone
Lead
Arsenic, Copper, Mercury
Lead, Arsenic, Mercury
Copper, Mercury, Lead
Iron
Iron

10. Dimercaprol (BAL)
➢ Synthesized during the world war II by Britisher’s as an antidote to arsenic war gas lewisite
➢ Oily, pungent smelling, viscous fluid
➢ It is administered i.m. in oil (arachis oil)
➢ SH ligands of dimercaprol compete with - SH groups of enzymes for heavy metal
➢ Excess of dimercaprol should be maintained in plasma
➢ Dimercaprol - metal complex is stable and excreted in urine
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11. Uses
➢ For the treatment of Arsenic & Mercury poisoning
➢ As an adjuvant to Calcium disodium edetate in lead poisoning
➢ As an adjuvant to Pencil amine in copper poisoning and in Wilson’s disease
➢ Contraindicated in iron and cadmium poisoning
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12. Adverse effects
Frequent, dose related, but generally not damaging
➢ Rise in BP & Tachycardia
➢ Sweating , Tingling & Burning sensations
➢ Inflammation of mucous membranes
➢ Cramps
➢ Headache
➢ Anxiety 12

13. DMSA (Succimer)
Dimercaprol analogue
➢ Water soluble, less toxic and orally effective
➢ Marketed in USA and some other countries, not in India for the treatment of lead
intoxication
➢ Side effects are nausea, anorexia & loose stools
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14. DMPS (Unithiol)
Dimercaprol analogue
➢ Water soluble, less toxic
➢ Can be administered orally as well as IV
➢ Used for severe acute poisoning by mercury & arsenic
➢ Also effective in the treatment of lead poisoning
➢ Adverse effects are low, except for mild self-limited urticaria
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15. Disodium edetate ( Na2+ EDTA)
➢ It is a disodium salt of EDTA
➢ Potent chelator of calcium
➢ Causes tetany on i.v. injection (but not on slow infusion)
➢ Can be used for emergency control of hypercalcaemia (rare) 50mg/kg i.v. over 2 - 4hours
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16. Calcium disodium edetate
➢ Calcium chelator of Na2+ EDTA
➢ Has a high affinity for lead
➢ Most important use is lead poisoning
➢ Poorly absorbed from GI
➢ i.m. is very painful - i.v. preferred
➢ Not metabolized
➢ Excreted by glomerular filtration and tubular secretion
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17. Adverse effects
➢ Does not produce tetany - relatively safe
➢ Kidney damage with proximal tubular necrosis - but dose related
➢ An acute febrile reaction with chills
➢ Body ache
➢ Malaise
➢ Tiredness occurs in some individuals
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18. Pencillamine
Dimethyl cysteine
➢ Water soluble degradation product of penicillin
➢ D - isomer is used - relatively non toxic compared to l - isomer
➢ Easily absorbed from GIT
➢ Little metabolized, excreted in urine and faeces
➢ It has strong copper chelating property and was used in 1956 for Wilson’s disease
It selectively chelates Cu, Hg, Pb & Zn
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19. Uses
Wilson’s disease (Hepatolenticular degeneration)
➢ Copper/ mercury (alternate to BAL & DMSA) poisoning
➢ Adjuvant to calcium disodium Edetate in lead poisoning but DMSA is preferred
➢ Cystinuria and cysteine stones
➢ Scleroderma - benefits by increasing the soluble collagen
➢ It was used as a disease modifying drug in rheumatoid arthritis, but now replaced by safer
drugs
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20. Adverse effects
▪ Short term administration - does not cause much problem (cutaneous reactions)
▪ Long term use - produces pronounced toxicity
▪ Dermatological, renal, haematological & collage tissue toxicities
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21. Trientine
➢ Chelates copper and is used in Wilson’s disease
➢ May be less toxic than pencil amine
➢ However, in animal studies it has been found to be teratogenic
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22. Desferrioxamine
▪ Ferrioxamine obtained from actinomycete, long chain iron containing complex
▪ Chemical removal of iron from it yields desferrioxamine
▪ 1gm is capable of chelating 85mg of elemental iron
▪ Low affinity for calcium
▪ Little of orally administered desferrioxamine is absorbed
▪ Parenterally - partly metabolized, rapidly excreted in urine
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23. • Acute iron poisoning: mostly in children, important and life saving
• Transfusion siderosis
Adverse effects:
• Hypotensive shock due to histamine release
• Abdominal pain, muscle cramps, fever & dysuria
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24. Deferiprone
➢ Orally active
➢ Used in transfusion siderosis
➢ Somewhat less effective, alternate to injected desferrioxamine
➢ Also indicated in iron poisoning (less effective than desferrioxamine) & iron load in liver
cirrhosis
➢ Side effects - Anorexia, vomiting, altered taste, joint pain, reversible neutropenia,
rarely agranulocytosis
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25. ‘’Conclusion
Primary goals of chelation therapy
➢ To reduce metal retention
➢ To decrease morbidity and mortality
➢ To prevent complications
➢ Many efficient chelators exist today
➢ Administer less toxic chelator when possible
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26. ‘’Conclusion
Unsolved issues
➢ Chelation of cadmium, chromium, platinum
➢ Chelation therapy in infants, children and during pregnancy
➢ Combined chelation therapy (chelators, vitamins, minerals)
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27. Thank You