Chelating agents

Overview
Chelating agents are compounds that bind tightly to metal ions, forming stable, water-soluble complexes (chelates) that can be excreted from the body. They are used to treat heavy metal poisoning, manage iron overload, and in certain diagnostic or therapeutic applications where removal or redistribution of metals is beneficial. The choice of chelating agent depends on the specific metal involved, the patient’s condition, and the drug’s pharmacokinetic and safety profile.

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Mechanism of Action

• Chelating agents have two or more electron-donating groups (e.g., hydroxyl, carboxyl, amine, thiol) that coordinate with a metal ion at multiple sites, forming a ring-like complex.

• This reduces the metal’s reactivity, decreases its binding to tissues, and enhances renal or biliary excretion.

• Some agents are selective for certain metals; others bind a wider range.

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Major Chelating Agents and Uses

1. Calcium Disodium EDTA (CaNa₂EDTA)

   • Target Metals: Lead (preferred for severe lead poisoning in children), zinc, manganese

   • Route: IV, IM

   • Notes: Must be used with calcium to prevent hypocalcemia; not effective for mercury or arsenic.

2. Dimercaprol (British Anti-Lewisite, BAL)

   • Target Metals: Arsenic, mercury, gold, lead (in combination with EDTA)

   • Route: Deep IM injection in peanut oil

   • Notes: Toxic at high doses; causes hypertension, tachycardia, nausea; contraindicated in iron or cadmium poisoning (worsens toxicity).

3. Succimer (DMSA, Dimercaptosuccinic Acid)

   • Target Metals: Lead (oral agent of choice for moderate poisoning), mercury, arsenic

   • Route: Oral

   • Notes: Less toxic and easier to use than BAL; suitable for outpatient pediatric use.

4. Penicillamine

   • Target Metals: Copper (Wilson’s disease), lead (adjunct), mercury

   • Route: Oral

   • Notes: Also used for cystinuria; may cause hypersensitivity reactions, bone marrow suppression, proteinuria.

5. Deferoxamine

   • Target Metal: Iron (acute iron poisoning, chronic iron overload from transfusions)

   • Route: IV, IM, SC

   • Notes: Binds ferric iron (Fe³⁺); excreted in urine (reddish color); long-term use can cause auditory/visual toxicity.

6. Deferasirox / Deferiprone

   • Target Metal: Iron (chronic overload in transfusion-dependent anemias)

   • Route: Oral

   • Notes: Used for long-term chelation in thalassemia, sickle cell disease; monitor for hepatic/renal toxicity.

7. Trientine

   • Target Metal: Copper (Wilson’s disease alternative to penicillamine)

   • Route: Oral

   • Notes: Fewer hypersensitivity reactions than penicillamine but may cause iron deficiency.

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Therapeutic Indications

• Heavy metal poisoning (lead, arsenic, mercury)

• Chronic iron overload (e.g., in thalassemia, sickle cell anemia)

• Wilson’s disease (copper overload)

• Certain diagnostic procedures (e.g., radionuclide decorporation)

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Contraindications (vary by drug)

• Hypersensitivity to the agent

• Severe renal or hepatic impairment (for some agents)

• Certain metal poisonings (e.g., dimercaprol contraindicated in iron or cadmium toxicity)

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Precautions

• Chelation can deplete essential trace elements (zinc, copper) — monitor and supplement if necessary

• Monitor blood counts, liver, and kidney function during prolonged therapy

• Risk of redistribution of metals to the CNS with some agents (e.g., dimercaprol with lead if not combined with EDTA)

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Adverse Effects (class-dependent)

• Gastrointestinal upset, rash, allergic reactions

• Nephrotoxicity or hepatotoxicity with prolonged use

• Hypotension (rapid deferoxamine infusion)

• Bone marrow suppression (penicillamine, trientine)

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Drug Interactions

• Mineral supplements (iron, zinc, copper) can reduce efficacy; separate administration

• Concomitant nephrotoxic drugs increase renal risk

• Certain antacids may reduce oral chelator absorption