A Power point presentation on "Chelating agents" suitable for UG MBBS level Medical students

1. Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, Shillong

2. 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 exretable complexes with toxic
metals
▫ Contains 2 or more reactive groups (ligand) such that can hold
metal from two sides
▫ Ligand: is a functional group capable of forming coordinate
bond in which both the shared electrons are donated by ligand –
mostly O, N or S atom in hydroxyl, carboxyl, keto, sulhydryl,
disulfide, amino or phosphate groups.

3. 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

4. Ideal chelating agent
1. Ideal chelating agents have higher affinity for toxic
metals than for body Ca++ (readily available in plasma
and ECF)
2. Should also have higher affinity for toxic metals than
body ligands
3. Ideally should be water soluble and distribution should
correspond to that of the metal intended to
Interval of administration between exposure to metals and
chelating agents should be less

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

6. BAL or Dimercaprol:
• World War-II as anti-Lewisite
• Oily , pungent smelling, viscous liquid, water insoluble
Pharmacological actions:
▫ heavy metals like As, Hg, Au, Bi, Ni, Sb and Cu etc. attacks (-SH),
an important component of CoA and prevents formation of acetyl
CoA leading to disaster - BAL binds with these metals and
protects CoA
▫ 1:1 Vs 2:1 Complex (more stability) – excess amount is required
 Metal-BAL complex dissociates quickly releases metal slowly – BAL
partly metabolized in the body
 BAL is oxidized in the body
▫ Alkalinazation of urine is required – in acid urine complex
dissociates faster
▫ However dose dependent toxicity – no large dose at time

7. 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
1. As adjuvant to Cal. disod.
edetate in Lead Poisoning
2. 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

8. Penicillamine
• Degraded product of Penicillin (beta dimethylcysteine)
• Prepared by alkaline hydrolysis of benzyl penicillin – d-penicillamine
• Strong Cu chelating property - useful in Cu poisoning
• MOA is same as others – selective chelating of Cu, Hg, Pb and Zn
• Absorbed orally - available as 250 mg capsules, metabolized in liver and
excreted in urine
• Uses:
▫ Wilson`s disease: hepatolenticular degeneration due to genetic deficiency of
ceruplasmin (Cu deposition in body) – life long therapy (0.5-1 gm daily)
▫ Cu and Hg (alternative) Poisoning
▫ Chronic Pb poisoning (adjuvant to edetate)
▫ Cystinuria and cystine stones
▫ Scleroderma: benefits by increasing soluble collagen
• 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.

9. Calcium disodium edetate
(CaNa2EDTA)
• Calcium chelate of Na2EDTA is used clinically instead of
Na2EDTA – ethylene diamine tetracetic acid
• High affinity for Pb, Zn, Cd, Mn, Cu and some radioactive
metals
• MOA: Removes the metals by exchanging with Ca++
• Highly ionized – not absorbed orally and that’s why acts
extracellularly – rapidly excreted via kidney
• 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

10. Desferrioxamine (Acute Iron Poisoning)
• Ferrioxamine – an Iron containing compound –
actinomycetes
▫ Chemical removal of Iron – desferrioxamine
▫ 1gm = 85 mg of elemental iron
• MOA: Desferrioxamine binds with ferric Iron – stable non-
toxic compound
▫ Also removes Iron (loosely bound) from haemosiderin and
ferritin, but not Hb and Cyt.
▫ Low Ca++ affinity
• 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

11. Acute Iron Poisoning
• Common in infants and children – 10 to 20 mg iron tablets or
equivalent (above 60 mg/kg)
• Symptoms: Vomiting, abdominal pain, haematemesis, diarrhoea,
lethargy, cyanosis, dehydration, acidosis, shock, convulsion and
death
• Pathology: haemorrhage & inflammation in gut, hepatic necrosis
and brain damage
• Aim of treatment: To induce vomiting or gastric lavage with
sodibicarb, egg yolk or milk - orally to complex Iron
• Desferrioxamine: To bind the iron already present
▫ 50 mg/kg IM/SC every 4-12 Hrly till serum levels of Iron falls below
200mcg/dl
▫ Or IV 10-15 mg/kg/hr till serum Iron falls below 200 mcg/dl
▫ Supportive therapy with fluid and correction of acidosis etc.

12. Deferiprone
• Orally active Iron chelator
• Given in transfusion siderosis in thalassemia
patients
• 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.

13. Important
• Short Questions on – BAL, Penicillamine,
Calcium edetate and Deferiprone – all are
important
• Acute Iron Poisoning management -
Desferrioxamine

14. Thank you - - and
All the Best