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

POISON

ANTIDOTE

COMMMENTS

Acetaminophen

Acetylcystiene

Given before 24 hours ingestion activated charcoal

Lead

Calcium-EDTA

Chelating agent

arsenic?/ other metals Dimercaprol D- penicillamine

Chelating agent

Lead, mercury, arsenic

Chelating agent

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

• 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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