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 Acetaminophen

ANTIDOTE Acetylcystiene

COMMMENTS Given before 24 hours ingestion activated charcoal Chelating agent Chelating agent Chelating agent

Lead arsenic?/ other metals Lead, mercury, arsenic

Calcium-EDTA Dimercaprol D- penicillamine succiner

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 painful TOXICITY: 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

 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 degradation Indication: copper poisoning (wilsons dse) severe rheumatoid arthritis Adv: 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 feces INDICATION: 2003- FDA approved treament for cesium Dosage: 3g orally 3x/day Serial monitoring/ fecal and urine Contipation mmay occur

Reference
Bertman G. Katzung (lange) John joseph fenton ( toxicology) Steven G. Gilbert (a small dose of toxicology)

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