Chelating agents

1. Chelating agents

2. • Chelating agents 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

3. • 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.

4. MOA
• Heavy metals exert their toxic effects by
combining with and inactivating functional
groups (ligands) of enzymes and important
biomolecules - sulfhydryl, hydroxyl,
carboxyl etc. leading to inactivation
• Chelating agents compete with body ligands
for the heavy metal – also differ in affinity for
different metals

5. • 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

6. 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

7. Classification
Drug
EDTA ----------------
Dimercaprol ---------------
Succimer ---------------
Penicillamine -------------
Trientine -------------
Deferrioxamine -----------
Deferiprone -----------
Used against
Lead
Arsenic,copper,mer.
Lead,arsenic,mercury
Copper,mercury,lead
Copper
Iron
Iron

8. BAL or Dimercaprol:
• World War-II as anti-Lewisite
• Oily , pungent smelling, viscous liquid,
water insoluble
Pharmacological actions:
–heavy metals like As, Hg, Au, Ni 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

9. –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

10. 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

11. • 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

12. 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

13. • 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

14. 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.

15. Disodium edetate (Na2 EDTA)
• It is a disodium salt of EDTA
• Potent chelator of calcium
• Causes tetany on i.v. injection (but not on
slow infusion)
• Can be used for emergency control of
hypercalcaemia (rare) 50mg/kg i.v. over 2-
4hours

16. 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

17. • 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

18. 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

19. Desferrioxamine (Acute Iron
Poisoning)
• Ferrioxamine – an Iron containing compound –
actinomycetes
– Chemical removal of Iron – desferrioxamine
– 1gm = 85 mg of elemental iron

20. • 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
•

21. 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

22. 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

23. • 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.

24. 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.