Chelating agents are drugs that form ring structures by binding to metallic ions. They are used to treat heavy metal intoxications by preventing metals from binding to biological ligands. An ideal chelator has the ability to reach sites of metal storage and form stable, non-toxic complexes that are excreted easily. It should have low affinity for essential metals like calcium and zinc. Common chelating agents include penicillamine, trientine, EDTA, deferoxamine, deferiprone, succimer, DMPS, and dimercaprol. Each agent has different mechanisms of action, routes of administration, targeted metals, and side effect profiles. Chelation therapy helps mobilize and eliminate toxic heavy metals from

1. CHELATING
AGENTS
DR GEETHA

2. DEFINITION
● Drugs which complex metallic ions,forminf ring
structures within their molecule(greek chele
=crab;the compound holds the metal like a crab's
claw)
● Prevents metals binding to biological ligands
● Used in treatment of acute heavy metal
intoxications

3. PROPERTIES OF IDEAL
CHELATOR
● Ability to reach sites of metal storage and form
stable and non toxic complexes with toxic metals
and should be readily excreted
● A low affinity for essential metals like calcium and
zinc also is desirable,because they often act
through competition with these metals
● High solubility in water and resistance to bio
transformation
● They have atleast two reactive groups(ligands)
which hold the metal from atleast two sides so that
a ring is formed.(5-7 membered ring is most
stable)

5. DISADVANTAGES
● Not useful in chronic exposure ,may increase the
neurotoxic effects

6. Useful CHELATING AGENTS
● PENICILLAMINE;
TRIENTINE
● EDTA
● Disodium edetate
● Calcium disodium
edetate
● DEFEROXAMINE
● DEFERASIROX
● SUCCIMER(dimercapto
succinic acid)
● DMPS
● DIMERCAPROL;
(BRITISH ANTI
LEWISITE)

7. PENICILLAMINE
● Copper chelating agent
● It is dimethyl cysteine ,obtained as a degradation
product of penicillin
● Selectively chelates Cu,Hg,Pb and zn
● Given orally
● Used in wilson's disease,cystinuria, rheumatoid
arthritis,scleroderma

8. ABSORPTION AND
EXCRETION:-
● Well absorbed from git
● It also combines chemically with cysteine to form
a stable soluble,readily excreted complex
● Hepatic biotransformation is responsible for
degradation
● The d-isomer is used therapeutically,beacuse the l-
isomer produce optic neuritis and are more toxic

9. TOXICITY
● Long term use induces cutaneous lesions and
myasthenia gravis
● Leukopenia,aplastic anemia,agranulocytosis
● Renal toxicity is seen
● CONTRAINDICATIONS
● Pregnancy
● Renal insufficiency
● H/o of agranulocytosis

10. TRIENTINE(trietheylenetetrami
ne dihydrochloride)
● Acceptable alternative to penicillamine and orally
effective
● Its cupriuretic agent in patients with wilson's
disease
SIDE EFFECTS:-
● Iron deficiency

11. DESFEROXAMINE
● It has high affinity for ferric ironand very low
affinity for calcium and is given parenterally
● 1g is capable of chelating 85mg of elemental iron
● For severe iron toxicity ,IV route is preferred
● For chronic iron intoxication,transfusion siderosis
(thalassemia) IM is preffered
● Also used to chelate aluminuim in dialysis patients
● Its metobolised by plasma enzymes and excreted
readily in urine
● Used in acute iron poisioning :mostly in children

12. ADVERSE EFFECTS:
● Desferroxamine can
cause histamine
release = fall in
bp,flushing,itching,urti
caria,rash
CONTRAINDICATIONS:
-
● RENAL INSUFFIENCY

13. DEFERIPRONE
● Orally active iron chelator which simplified the
treatment of transfusion siderosis in thalasemia
patients
● Excessive hemolysis occurs in these patients ,so
they should be given repeated blood transfusions
=iron overload
● Oral deferiprone is less effective compared to
injected desferroxamine but has less side effects
● Indicate din acute iron poisioning and for iron
overload in liver cirrhosis
● SIDE EFFECTS:anorexia,vomiting,altered
taste,reversible neutropenia

14. EDTA (Ethylene diamine tetra
acetic acid)
● Available as edetate calcium disodium used in
acute lead intoxication along with dimercaprol
Mechanism of action :-
● Metal ions with higher affinity than calcium will be
chelated,mobilzed and usually excreted
● Charged at physiological pH,so doesn't penetrate
cells,<5% is absorbed from git
● Its highly ionized ,therefore distributed only
extracellularly
● Administered intravenously,
● Excreted in urine through glomerular filtration

15. EDTA
Toxicity :-
● Nephrotoxic causes
proximal tubular
necrosis
● Rapid IV administration
causes hypocalcemic
tetany
Side effects:-
● Malaise,chills body
aches
● Fatigue
● Excessive thirst

17. BAL
Mechanism of action :-
●
Bal forms complexes between two sulfhydryl
groups and metals and delivered to kidneys and is
toxic to kidneys
●
Its dissociates in acidic urine and metal is
released in kidneys,so urine is alkanized during
dimercaprol therapy

18. BAL
● It limits toxicity from
arsenic,gold,mercury
● Given as deep IM in
peanut oil
Toxicity:-
● Rise in bp
accompanied with
tachycardia &returns to
normal in 2hrs
● Not used in chronic
exposures to heavy
metals because it
doesnot prevent
neurotoxic effects

19. SUCCIMER
(2,3 dimercapto succinic acid-
DMSA)
● Orally effective chelator against lead
● Its water soluble and doesn't mobilise metals to
brain
● Doesn't significantly chelate essential metals ,so
has better toxicity profile
MECHANISM OF ACTION:-
● Forms complex with lead,succimer-lead chelate is
eliminated both in urine and bile through entero
hepatic circulation

20. Side effects:-
● Nausea,vomiting,diarhhoea and loss of appetite
● In USA ,Succimer is approved for treatment of
children with blood levels >45 mcg/dl
● Not used in India

21. DMPS
● Approved only in germany
● Chelator of lead,arsenic and especially mercury

22. ●
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