Chelating agent for iron poisoning

Chelating agents are compounds that bind to metal ions and help remove them from the body, often used in cases of iron poisoning (also known as iron overload or iron toxicity). Iron poisoning typically occurs when there is an excessive accumulation of iron in the body, often due to accidental ingestion of iron-containing supplements, or chronic conditions like hemachromatosis. In cases of acute iron poisoning, it is critical to remove the excess iron as quickly as possible to prevent organ damage, especially to the liver and heart.

Here are the main chelating agents used for iron poisoning:

1. Deferoxamine (Desferal)
Deferoxamine is the most commonly used chelating agent for acute iron poisoning. It works by binding to free iron in the bloodstream and forming a stable complex, which is then excreted via the kidneys.

Mechanism: Deferoxamine binds to ferric iron (Fe³⁺), forming a water-soluble complex that can be excreted in the urine. It primarily removes excess iron from the tissues and organs.
Administration:
Intravenous (IV) or intramuscular (IM) administration is typical, especially in severe cases of poisoning.
It can also be given as a continuous infusion for hours or days, depending on the severity of the poisoning.
The dose and duration depend on the level of iron toxicity and the response to treatment.
Indication: Used in acute iron poisoning and chronic iron overload (e.g., in thalassemia patients).
Side Effects:
Ototoxicity (hearing impairment) and visual toxicity (blurred vision or retinal toxicity).
Hypotension and respiratory distress in severe cases (usually with high doses).
Allergic reactions and local reactions at the injection site.
2. Deferasirox (Exjade, Jadenu)
Deferasirox is an oral iron chelator used primarily for chronic iron overload, such as in patients with thalassemia or sickle cell disease who require regular blood transfusions.

Mechanism: Deferasirox selectively binds to ferric iron (Fe³⁺) and forms a complex that is then excreted in the stool.
Administration: Oral tablets or dispersible tablets taken once daily.
Indication: Chronic iron overload conditions due to blood transfusions. It is not commonly used for acute poisoning but may be used in mild to moderate iron toxicity or after deferoxamine treatment to maintain normal iron levels.
Side Effects:
Gastrointestinal issues (nausea, diarrhea, abdominal pain).
Liver toxicity (elevated liver enzymes).
Renal toxicity (kidney dysfunction), so kidney function should be monitored during treatment.
3. Deferiprone (Ferriprox)
Deferiprone is another oral iron chelator, used to treat chronic iron overload, typically in patients with thalassemia.

Mechanism: Deferiprone binds to ferric iron and forms a soluble complex that is excreted primarily in the urine.
Administration: Oral administration, usually taken 2-3 times per day.
Indication: Chronic iron overload, especially for patients who cannot tolerate deferoxamine.
Side Effects:
Neutropenia (a decrease in white blood cells, which can increase the risk of infections).
Gastrointestinal symptoms (nausea, vomiting, abdominal pain).
Liver enzyme elevation.
4. EDTA (Ethylenediaminetetraacetic acid)
EDTA is a general chelating agent that can bind to a variety of metal ions, including iron. However, it is more commonly used for lead and other heavy metal poisoning. In some cases of iron toxicity, EDTA may be used as a secondary chelating agent if the standard agents (like deferoxamine) are unavailable.

Mechanism: EDTA binds to metal ions (including Fe²⁺ and Fe³⁺) and forms a chelate that is excreted via urine.
Administration: Typically administered intravenously or intramuscularly.
Indication: Used in some cases of acute iron poisoning or in patients with heavy metal toxicity, but is not as effective as deferoxamine specifically for iron.
Side Effects:
Kidney toxicity (requires careful monitoring of kidney function).
Electrolyte imbalances (e.g., calcium depletion).
Treatment Protocol for Iron Poisoning
Initial management:
Gastric lavage or activated charcoal may be administered if the patient presents within a short time after ingesting a large amount of iron, although activated charcoal is ineffective in iron poisoning.
Supportive care: Monitor vital signs, maintain airway, provide oxygen if necessary, and correct any shock or metabolic disturbances.
Chelation therapy:
If the patient presents with severe iron toxicity (e.g., serum iron levels above a certain threshold, symptoms of shock, liver or heart failure), deferoxamine is typically administered.
Deferoxamine should be started early to effectively remove iron from the body and reduce the risk of long-term organ damage. In some cases, deferoxamine is used alongside other therapies like IV fluids and blood pressure support.
Monitoring:
Serum iron levels and transferrin saturation are monitored to assess the severity of toxicity and guide chelation therapy.
Kidney function and liver enzymes should be closely monitored, especially when using deferasirox or deferiprone for chronic overload or prolonged treatment.
Conclusion
For iron poisoning, the first-line treatment is usually deferoxamine, especially in acute cases of toxicity, due to its high specificity for iron and ability to effectively remove iron from the body. Deferasirox and deferiprone are used more for chronic iron overload conditions but can be considered in certain cases of acute toxicity when intravenous chelators are not available. It is important to initiate treatment as soon as possible in cases of iron poisoning to minimize the risk of organ damage, particularly to the liver and heart.