This document discusses chelating agents used to treat heavy metal poisoning. It describes how chelating agents work by binding to metal ions through groups like -SH or -OH, forming stable water-soluble complexes that can be excreted. Several chelating drugs are mentioned, including dimercaprol, DMSA, DMPS, EDTA, penicillamine, desferrioxamine, and deferiprone. Their uses in treating various heavy metal toxicities like lead, arsenic, mercury, copper, and iron poisoning are outlined. Side effects of the drugs and dosing information is also provided. The goals of chelation therapy to reduce metal retention and prevent complications of toxicity are noted in conclusion.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.

2. Chele-claw- chelating agents usually contain polar
groups such as –SH or –OH which can bind a metal ion
as endogenous ligands bind to metal ion and form
stable non-toxic water soluble complexes
Relative affinity of chelator to heavy metal
Distribution of chelator in body
Capacity to mobilize the complex
Half life of heavy metal
Time after exposure

3. Heavy metals combines with
one or more reactive groups (Ligands)
Oxygen (-OH, -COO, -OPO)
Nitrogen (-NH2, -NH)
Sulphur (-SH, -S-S)
Hamper physiological function
Enzyme inhibition, Oxidative stress

4. Chelating agents useful as drugs are:
Dimercaprol (BAL)
Dimercaptosuccinic acid (DMSA)
Dimercaptopropane sulfonic acid (DMPS)
Disodium edetate
Calcium disodium edetate
Pencillamine
Desferrioxamine
Deferiprone

5. Drug
EDTA, DMSA ----------
Dimercaprol ---------------
Succimer (DMSA)
DMPS --------
Penicillamine, -------------
Trientine
Desferrioxamine -----------
Deferiprone -----------
Used against
Lead
Arsenic, copper, mercury
Lead, arsenic, mercury
Copper, mercury, lead
Copper
Iron
Iron

6. It was synthesized during the world war II by Britishers
as an antidote to arsenic war gas lewisite
Oily, pungent smelling, viscous fluid
It is administered i.m in oil (arachis oil)
-SH ligands of dimercaprol compete with –SH groups of
enzymes for heavy metal
Dimercaprol –metal complex is stable and excreted in
urine( urine should be kept alkaline to prevent
dissociation)

7. Uses:
For the treatment of arsenic and mercury poisoning
As adjuvant to Cal. disod. Edetate in lead poisoning
As an adjuvant to pencillamine in copper poisoning
and in Wilson’s disease
Contraindicated in iron and cadmium poisoning
As BAL-Fe-complex is toxic

8. Adverse effects:
Frequent, dose related, but generally not damaging
Rise in BP, tachycardia, tingling and burning sensations,
inflammation of mucous membranes, sweating,
cramps, headache and anxiety
Dose 5mg/kg followed by 2-3mg/kg 4hr/2days

9. 2,3 Dimercapro Succinic acid
Dimercaprol analogue
Water soluble, less toxic and orally effective
Specific for the treatment of lead intoxication and
needs no combination with edetate calcium disodium
Effective in allevating acute toxicity and preventing
distribution of orally administered mercury
Side effects are nausea, anorexia, raised serum amino
transferases and loose motions
Dose-10mg/kg 8hrly/5days

10. Dimercaptopropane sulfonic Acid
Dimercaprol analogue
Water soluble, less toxic
Can be administered orally as well as IV
Used for severe acute poisoning by mercury and arsenic
Also effective in the treatment of lead poisoning
Dose-3-5mg/kg 4hrly by i.v in 20min
Adverse effects are low, except for mild self-limited
urticaria, IV infusion may cause hypotension

11. Ethylene Diamine tetra acetic acid disodium calcium salt
It is a disodium salt of EDTA
EDTA is a potent chelator for Ca+ and produces life
threatening tetany.
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

12. Ethylene Diamine tetra acetic acid disodium calcium salt
It is a disodium salt of EDTA
Potent chelator of many divalent(lead, zinc, cadmium,
manganese and mercury). In this exchange process, its own
calcium is displaced from the molecule
Calcium chelator of Na2 EDTA
Has a high affinity for lead
Most important use is lead poisoning
Poorly absorbed from GI –given i.m or i.v.
i.m is very painful –i.v. preferred
Not metabolized
Excreted by glomerular filtration and tubular secretion

13. DTPA-Diethylene Triamine Penta Acetic Acid
Is useful in removing radioactive uranium and
plutonium
Adverse reactions:
Does not produce tetany –relatively safe
Nephrotoxicity-Kidney damage with proximal tubular
necrosis –but dose related
An acute febrile reaction with chills, body ache,
malaise, tiredness occurs in some individuals
Dose- 50-75mg/kg /day i.v

14. Dimethylcysteine is a water soluble degradation
product of penicillin
D –isomer is used-relatively non toxic compared to l –
isomer (optic neuritis) is used in copper poisiining
Easily absorbed from GIT
Little metabolized, excreted in urine and faeces
It has strong copper chelating property and was used
in 1956 for Wilson’s disease
It selectively chelates Cu, Hg, Pb and Zn

15. Wilson’s disease (hepatolenticular degeneration)
Copper/ mercury (alternate to BAL & DMSA) poisoning
Adjuvant to cal. disod. Edetate in lead poisoning but
DMSA is preferred
Cystinuria and cystine stones-it complexes with cystine
and prevents precipitation in the urinary tract
Scleroderma –benefits by increasing the soluble
collagen
It was used as a disease modifying drug in rheumatoid
arthritis, but now replaced by safer drugs

16. Short term administration –does not cause much
problem (cutaneous reactions)
Long term use –produces pronounced toxicity
hypersensitivity
Dermatological, renal,
Hematological-leukopenia, aplastic anemia
and collagen tissue toxicities
Dose-0.5-1g daily in divided doses

17. Triethyl tetramine dihydrochloride
Less toxic alternative to pencillamine in copper
poisoning
Also effective orally
1gm BD on empty stomach
Adverse effect
Iron deficiency

18. Ferrioxamine derivative devoid of iron
Obtained from actinomycete
High affinity for Fe3+
1gm is capable of chelating 85mg of elemental iron
Unique property that it can remove iron from ferritin,
haemosiderin and to some extent from transferrin but not
from hemoglobin or cytochrome
Low affinity for calcium
Little of orally administered desferrioxamine is absorbed
Parenterally –partly metabolized, rapidly excreted in urine

19. Uses:
Acute iron poisoning: mostly in children, important
and life saving
Transfusion siderosis-blood transfusion to patients of
thalassemia
With hemodialysis in treatment of aluminium toxicity
in renal failure
Adverse effects:
Hypotensive shock due to histamine release
Abdominal pain, muscle cramps, fever and diarrhoea
Dose- i.v ,10-15mg/kg/hr infusion

20. Orally active iron chelator
Used in transfusion siderosis
Somewhat less effective, alternate to injected
desferrioxamine
Side effects and cost of treatment are reduced
Also indicated in iron poisoning (less effective than
desferrioxamine) and iron load in liver cirrhosis

21. Side effects are:
Anorexia, vomiting, altered taste, joint pain, reversible
neutropenia, rarely agranulocytosis
Long term safety is not yet known
Dose-50-100mg/kg

22. Oral iron chelator
For chronic iron overload- beta thalassemia
High affinity for iron, less affinity for zinc, copper
Iron deferasirox chelator complex is secreted through
bile and excreted in faeces
DEXRAZOXANE-used to protect against cardiotoxic
drugs—anthracyclines-doxorubicin, daunorubicin

23. Primary goals of chelation therapy:
To reduce metal retention
To decrease morbidity and mortality
To prevent complications
Administer less toxic chelator when possible
Unsolved issues:
Chelation of cadmium, chromium, platinum…
Chelation therapy in infants, children and during pregnancy
Combined chelation therapy

24. THANKYOU
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