Chelating Agents

CHELATING AGENTS

Chelating agents are drugs which complex metallic ions, forming ring like structures within their molecules. form stable, nontoxic and easily excreted complexes with toxic metals. Heavy metals exert their toxic effects by combining with and inactivating functional groups of enzymes or other critical biomolecules.

chela "claw" • Heavy metals exert their toxic effects

by combining with one or more reactive groups (ligands) • Essentially blocking normal physiological functions. Heavy-metal antagonists (chelating agents) Designed specifically to compete with these groups for the metals

An ideal chelating agent

• A low affinity for Ca2+ also is

desirable because Ca2+ in plasma is readily available for chelation • And a drug might produce hypocalcemia despite high affinity for heavy metals. • Greater affinity for the metal than that of the endogenous ligands.

Chelating agents compete with body ligands for the heavy metal Dimercaprol Succimer Disodium edetate Calcium disodium edetate Pencillamine Deferoxamine

DIMERCAPROL Developed during world war II by the British as an antidote to lewisite – BAL

The two SH groups of dimercaprol bind with those metals which produce their toxicity by interacting with sulfhydryl containing enzymes in the body. Indications: As a single agent treatment of acute poisoning by arsenic and mercury Treatment of severe lead poisoning in conjuction with edetate calcium disodium As an adjuvant to pencillamine in Cu

Toxicity: hypertension,tachycardia,fever,pain at the injection site

SUCCIMER: water soluble analog of

dimercaprol Indications: lead poisoning in children Arsenic and mercury poisoning

UNITHIOL

EDETATE CALCIUM DISODIUM (Ca Na2 EDTA) higher affinity for lead, zinc, cadmium, copper and some radio active metals Chelates extracellular metal ions more effectively Indications: for the chelation of lead Zinc, manganese poisoning DTPA used for decorporation of uranium, plutonium Toxicity: kidney damage

d-PENCILLAMINE: selectively chelates copper, mercury, lead and zinc Can be used orally Indications: Wilson's disease Copper and mercury poisoning Chronic lead poisoning Severe RA Toxicity: hypersensitivity reactions

DEFEROXAMINE:very high affinity for iron Administered iv or im

Indications: chelator of choice for iron poisoning Transfusion siderosis Deferoxamine + hemodialysis useful in the treatment of aluminum toxicity in renal failure Toxicity: hypotension on iv administration ARDS Idiosyncratic reactions DEFERIPRONE: orally active iron chelator