This document discusses heavy metal poisoning and chelating agents used to treat it. It provides details on common heavy metals that cause poisoning like lead, mercury, and arsenic. It then explains the process of chelation where chelating agents form stable, water soluble complexes with metal ions to facilitate their excretion. Several chelating agents are mentioned, including BAL, EDTA, penicillamine, deferiprone, and desferioxamine, along with their mechanisms of action, uses, and side effects in treating heavy metal poisoning.

2. Heavy metals
80 metals in periodic table
They have corrosive & astringent properties
Acts as a protoplasmic poison by inhibiting essential enzyme
Ability to form complexes with important biological radical like
hydroxyl,Carboxyl,Keto,Sulfhydryl,disulphide,Amino, phosphate etc.
 Heavy metal poisoning is not uncommon
 Commonly implicated metals include- Pb, Hg, As,Cd

3. Drugs used to prevent heavy metal poisoning
Derived from Greek “Chele = Claws”
Chelation:- The process of an equilibrium reaction between a metal
ion & complexing agent what produce a stable, Non-ionized, Non-
toxic and water soluble complex which can be eliminated easily
Two or more reactive groups (ligands)
which can hold the metal from at least two sides so that a ring is formed

4.  Have two or more electronegative groups that forms stable
covalent bonds with the cationic metals
Chelating agents compete with body
Ligands for the heavy metals
 Clinical useful Chelating agents Affinity:-
↑↑ Affinity- Toxic metal
↓ ↓ Affinity- Calcium, body ligands

5. More affinity for metals than endogenous ligands
High solubility in water
Resistance to Biotransformation
Form non-toxic complex's with toxic metal
Cheap & easy to administered
Low affinity for Calcium
Easy excretion of chelating complex

6. Heavy metals
Cu,Fe,Mn,Pb
,Ca
Stable compound
Non-ionized , Non-metabolized
Non toxic
Water soluble
Chelating agents
Forming ring structure
Eliminated Via Kidney

7. Dimercaprol (BAL) & derivatives
EDTA derivatives -Disodium edetate, Calcium disodium edetate
 Calcium disodium DTPA (Diethylene triamine penta acetic acid)
Penicillamine
Desferrioxamine
Deferiprone

8. It is an oily, pungent smelling, viscous liquid
 Developed by Britisher during World War II as an Antidote for arsenic
containing war gases such as Lewisite
 Also called as British Anti-lewisite or BAL
 (-SH) group of BAL responsible for Chelation
 Analogue- 1.DMSA- (2,3 dimarcaptosuccinic acid )/ Succimer
2.DMPS-(2,3-Dimercapto-1-propanesulfonic acid)/ Unithiol

9. Mechanism:-
Form poorly dissociable complex with metal ions
Protect the SH enzymes
Prevent inhibition of enzyme
Pharmacokinetics:-
Can’t be given orally
Given by deep IM injection
t1/2-Short Peak plasma level in 1/2hrs -1 hr( IM)
Metabolized –liver glucuronide conjugated
 Excretion-As via urine (4-6hr)

10. Uses:-
 Poisoning by As(Acute & chronic), Hg, Bi, Au
Dose:- 5mg/kg stat, followed by 2-3 mg/kg every 4-8hrs × 2 days
and then BD ×10 days
# Alkalinisation of urine
 In lead poisoning:- As an adjuvant to Ca-Disodium edetate
 Wilson’s disease:- As an adjuvant to penicillamine

11.  Tachycardia, Hypertension
 Injection is painful and Chances of sterile abscess
 Allergic reaction
 Nausea, vomiting, headache
 Lacrimation, Conjuctivitis, Blepharospasm
 Sialorrhoea, muscle pain
(Antihistaminic given 30 min before injection )
Contraindication:-
 Iron & Cadmium poisoning

12. Water soluble analogue of dimercaprol
Advantage:-
- Less toxic
- orally effective
 Use- DOC for As,
 Also Hg, Pb poisoning.
 SE- Nausea, loose motion, Anorexia

13. 2,3-Dimercapto-1-propane-sulfonic acid
Water soluble analogue
Used orally and IV
Used in severe acute poisoning with As and Hg(Mercary)
IV-DMPS better efficacy over orally Succimer & IM-dimercaprol
Side effect-
Skin reaction

14. EDTA(Ethylene Diamine Tetra Acetic acid)
Chelates divalent or trivalent metals
invitro chelating agents
 Its is a disodium salt of EDTA
 Potent chelator of Ca
 Cause tetany on Iv injection (but not in slow infusion )-not preferred in Pb
poisoning
 Use:-
 Emergency control of hypercalcaemia
 Invitro anticoagulant
Disodium Edetate(Na2Edetate)

15. It is the calcium chelate of Na2 EDTA
Preferred over Na-edetate-Doesn’t deplete Ca++
Higher affinity for –Pb, Zn, Cd, Mn, Cu and some radio active metals
Mechanism:- Removes the metals by exchanging with Ca++
Higher ionized-not absorbed orally
Excretion-kidney
Iv route ,IM-route painful
No CNS penetration
USES:-
1.Pb-Poisoning:-preferred over Na2Edetate
2.Zn,Cu,Mn poisoning
Side effect:-
 Dose related kidney damage-
Toxic metal dissociate in tubule-
↑urine outflow
Chills, body ache,
Malaise,
Tiredness

16. Degraded product of Penicillin (β dimethyl cysteine)
(Cross reactivity with Penicillin)
Prepared by alkaline hydrolysis of benzyl penicillin
White crystalline, water-soluble having
strong Cu Chelating property
D-isomer –More potent than L-isomer (optic neuritis)
Pharmacokinetics:-
 Absorption- orally
 Metabolism-liver
 Peak plasma conc. In 1-3hr
 Excretion- urine & faeces

17. USES:-
-Wilson’s disease-
 An autosomal recessive disorder
 Deficiency of Ceruloplasmin, major Cu transport protein
 Absence of ceruloplasmin- Positive copper balance
 Cu deposition – liver, Substantia nigra, basal ganglia of brain
Rx-
-Cu-poisoning- DOC
-Hg poisoning- alternative drug to dimercaprol
-Cystinuria & cystine stones: It promotes the excretion of cysteine and prevents
its precipitation
-Scleroderma:- Penicillamine benefits by increasing soluble collagen

18. General toxicities:-
Headache, rash, fever, lymphadenopathy, dysguesia
Hematological toxicities
Aplastic anemia, agranulocytosis, thrombocytopenia
Autoimmune syndrome
Good pasture's Syndrome, Myasthenia Gravis
Others
Drug fever, polyarthritis, exfoliative dermatitis
Trientene:- Less potent but safer then d-penicillamine

19.  Obtained from streptomyces pilocus
 Chelator of iron
 Removes iron from hemosiderin and ferritin but not from haemoglobin and
cytochrome
M.O.A:-
Bind ferric iron to form ferrioxamine ( stable , water soluble)
P/K:-
Poorly absorbed after oral administration ,Used parenterally(IV/IM)
Uses:-
 Acute Iron toxicity:- in children DOC iv-desferioxamine
 Chronic iron poisoning(thalassaemia)- IM
 For chelation of aluminum in dialysis patient

20. A/E
Allergic reactions(pruritus, wheal, rash)
Dysuria, abdominal discomfort, diarrhoea
Cataract, neurotoxicity
Pulmonary syndrome
C.I
Renal disease
Pregnant women

21.  Orally effective but less effective then desferrioxamine
Use
 In patient in whom deferoxamine is C .I , unacceptable
or not tolerated
 Transfusion siderosis in thalasaemia
 Fe overload in liver cirrhosis
A/E
 Anorexia, Vomiting, Joint pain, Blood dyscrasia
 Dose 50-100mg/kg daily in 2-4 divided doses

22. Kkk
Drug Route of
Administrat
ion
Affinity for Uses C/I
BAL IM As As,Bi,Pb,Hg poisoning Fe,Cd
Na2Edetate I.v. Ca -Hypercalcemia
-an invitro anticoagulant
-
CaNa2Edetate Iv infusion Pb Pb,Zn, Mn, poisoning Hg poisoning
d-penicillamine Oral Cu -Wilson disease (Cu-
poisoning)
-Sceleroderma
-Cystinuria
desferioxamine IV,IM Fe Acute & chronic Fe poisoning Pregnancy,
Renal
insufficiency
Deferiprone Oral Fe Transfusion siderosis in
thalasaemia