Chelating Agents

CHELATING AGENTS

• from the greek word “claw”

• First chelating agent: BAL (british anti-lewiste)

CHELATION: organic molecules which form stable complexes with metal ions. Usually water soluble.

POISON ANTIDOTE COMMMENTS

Acetaminophen Acetylcystiene Given before 24 hours ingestion activated charcoal

Lead Calcium-EDTA Chelating agent

arsenic?/ other metals DimercaprolD- penicillamine

Chelating agent

Lead, mercury, arsenic

succiner Chelating agent

Chelating agents

• Drugs that prevent or reverse toxic effect of heavy metal on an enzyme or other cellular target.

• Determined by number of ligands groups. The greater the number, the stable the metal chelator complex.

DIMERCAPROL

• ( 2,3-dimercaptopropanol)• Also known as BAL : prototype• Given after Asenic exposure• IM/ often painfulTOXICITY: contraindicated in CHRONIC

POISONING (may redistribute mercury and

arsenic)

SUCCIMER

• (dimercaptosuccimic acid, DMSA)• Water analog of dimercaprol• Excreted in urine• USA: oral prepartion available.

Other place is IV.• Peaks at 3hours• Half life: 2-4 hours

mech: binds to ammino acid cystiene to form 1:1 and 1:2 mixed disulfide increasing excretion.

ADV: G.I. Problem, rashes, n/v, anorexia

EDTA• (ethylene diaminetetraacetic acid)• To prevent depletion of calcium,

preparation should only be CALCIUM DISODIUM SALT.

• I.V. Infusion• Contraindicated for anuria patient

2004: EDTA is FDA approved used to uranium ,plutonium , americanium, curium.

UNITHOL

• (dimercaptopropanesulfonic acid)DMPS• Water soluble to dimercaprol• 1st used in Russia(1958)/ used in USA

(1994)

• Bioavailability: oral (50%) peak:3-7 hr I.V. (80%) peak:20

hr

• Used against mercury, arsenic, lead.

TOXICITY: aqueous preparation (50mg/kg in sterile water every 4 hours over 20 mins (slow I.V.)

Oral Unithol: alternative use for succiner

• Adverse: limited to dermatologic reaction

-urticaria -Erythema multiform-Steven – Johnson syndrome

Note: rapid infusion can cause hypotension

PENICILLAMINE• (D-dimethycystiene)• White crystalline, water derivative of

penicillin• Readily absorbed on GUT and

Metabolic degradationIndication: copper poisoning (wilsons

dse) severe rheumatoid arthritisAdv: hypersensitivity/nephrotoxicity

DEFEROXAMINE• Isolated from STREP. PILOSUS

• Chelator of choice for iron poisoning

• Deferoxamine + hemodialysis = tx for aluminum toxicity of renal

failure

• may increase iron absorption if given orally

• Pathway is unknown

• Excreted in urine and causes ORANGE-RED color.

ADV:• Rapid I.V. = hypotension• Idiosyncratic reaction• Pulmonary comlication an

susceptibilty to infection ( seen in long term use)

PRUSSIAN BLUE

• (ferric hexacyanoferate )• Hydrated crystalline compund in

which Fe atoms are coordinated with cyanide groups in a cubic lattice structure.

MECH of ACTION: ion-exchange/ mechanical trapping on adsorption to certain univalent cations

• For cesium/ thallium• Elimination via fecesINDICATION: 2003- FDA approved

treament for cesiumDosage: 3g orally 3x/daySerial monitoring/ fecal and urineContipation mmay occur

Reference

• Bertman G. Katzung (lange)

• John joseph fenton ( toxicology)

• Steven G. Gilbert (a small dose of toxicology)

THANK YOU