Chelating Therapy

Azeem Imam
Mphil Pharmaceutics
UCP Lahore.
Definition
• Chelating therapy is the administration of
chelating agents to remove heavy metals from
the body.

• Treatment used for mercury, iron, arsenic, lead,

uranium and plutonium and other forms of toxic
metal poisoning.
Chelating Agents-What are they ???

• These are the compounds mainly used in heavy metal

poisoning
▫ Combines (complex) with metallic ions, forming ring structures
within their molecule (Chele – crab)

▫ Form stable, non toxic and easily excretable complexes with toxic
metals

▫ Contains 2 or more reactive groups (ligand) such that can hold

metal from two sides
Chelating Agents - MOA
• Heavy metals exert their toxic effects by combining with
and inactivating functional groups (ligands) of enzymes
and important biomolecules - sulfhydril, hydroxyl,
carboxyl etc. leading to inactivation
• Chelating agents compete with body ligands for the
heavy metal – also differ in affinity for different metals
• Chelating agents have high affinity for such metals and
combine with them to form non toxic and water soluble
complexes for elimination
• Possesses: –ve charged groups to attract +ve charged
toxic metals
Ideal chelating agent
1. Ideal chelating agents have higher affinity for toxic
metals than for body Ca++ (readily available in plasma)

2. Should also have higher affinity for toxic metals than

body ligands

3. Ideally should be water soluble

Interval of administration between exposure to metals and

chelating agents should be less
Chelating Agent - Classification
1. Dimercaprol (British anti-lewisite) or BAL – As,
Au, Bi, Ni, Sb and Hg poisoning
2. Dimercaptosuccinic acid (succimer) - Pb
3. Calcium disodium edetate (EDTA) – Pb
4. Disodium edetate
5. Penicillamine – Cu, Pb, Hg, Zn
6. Desferrioxamine – Iron overload
7. Deferiprone - Iron
BAL or Dimercaprol:

• World War-II as anti-Lewisite

• Oily , pungent smelling, viscous liquid, water insoluble

• Route of Administration
I/M
BAL – contd.
• Uses:
1. Poisoning by As, Hg, Au, Bi, Ni and Sb etc.
 Dose: Given I/M in 10% solution in oil - Available as 2 ml ampoules (50
mg/ml)
 Given deep IM 5 mg/kg stat every 4 Hrly for 2 days followed by increase in
interval after 3rd day
2. As adjuvant to Cal. disod. edetate in Lead Poisoning
3. As adjuvant to Penicillamine in Cu poisoning
• ADRs: Unpleasant nausea, vomiting, burning sensation of mouth,
inflammation of mucous membranes, sweating, cramps and lacrimation
etc.
• Contraindicated in hepatic damage and Cd and Fe poisoning
Penicillamine
• Metabolite of Penicillin (beta dimethylcysteine)
• Prepared by alkaline hydrolysis of benzyl penicillin – d-penicillamine
• Use:
In Cu poisoning
• MOA:
Selective chelating of Hg, Pb and Zn
• Absorbed orally - available as 250 mg capsules, metabolized in liver
and excreted in urine

• ADRs: Cutaneous dermatological reactions

▫ General: headache, sore throat, fever, rash, loss of taste, neuritis
▫ Blood: leucopenia, thrombocytopeenia, aplastic anaemia etc.
▫ Renal: nephrotic syndrome, haematuria
▫ Autoimmune: Myaesthenia like syndrome, diabetes, SLE etc.
Calcium disodium edetate (CaNa2EDTA)
• High affinity for Pb, Zn, Cd, Mn, Cu and some radioactive
metals

• Given IV as not absorbed in gut – IM is painful

• No CSF penetration

• Uses:
• Lead Poisoning – 1 gm is diluted in 200-300 ml of NS infused over 1 hr
twice daily – 2nd course repeated after 1 week
• Fe, Zn, Cu and Mn poisoning – but not in Hg poisoning

• ADRs: 1. Kidney damage – toxic metal dissociate in tubule –

should enhance urine flow; 2. febrile reactions – chills, body
ache, malaise, tiredness etc. 3. Anaphylactoid reactions
Desferrioxamine (Acute Iron Poisoning)

• MOA: Desferrioxamine binds with ferric Iron –

stable non-toxic compound

▫ Uses: SC or IV (0.5 gm/vial )

1. Acute Iron Poisoning
2. Transfusion siderosis: –– 0.5-1 gm/day SC or with
Blood transfusion 2 gm /unit of blood

• ADRs: Histamine release – fall in BP and alleric

reactions
Deferiprone

• Orally active Iron chelator

• Also used in iron poisoning but less effective

than desferrioxamine
• Dose: 50 to 100 mg/kg in daily in 4 divided
doses
• ADRs: Joint pain, anorexia, vomiting and
agranulocytosis etc.
Thank you - -

All the Best