Pharmacotherapy of chelating agents (Heavy metal antagonist)

Pharmacotherapy of chelating agents (Heavy metal antagonist) including pharmacology of chelating agents

1. DEPARTMENT OF PHARMACOLOGY
JNMC,Sawangi

2. PURPOSE STATEMENT
At the end of this lecture the student will be able to
Classify Chelating Agents
Explain Mechanism of Action
Describe Clinical Profile of Drugs

3. Sr.
No
Learning Objectives Domain
Leve
l
Criter
ia
Conditi
on
01.Define Chelating agent
Cognitiv
e
M.K - -
02.Classify of Chelating agent
Cognitiv
e
N.T.
K
- -
03.Describe Mechanism of action of drug
Cognitiv
e
M.K - -
04.
Describe Treatment of Poison
Cognitiv
e
M.K - -
At the end of this lecture student should be able to
M.K = Must know ; N.T.K = Nice to know ; D.T.K = Desirable to know

4. Introduction :
Heavy Metal acts as general protoplasmic poison and impairs the
cell function.
Have ability to form complexes with important biological radicals
like sulfhydryl hydroxyl, carboxyl, the amino acid, the imidazole.
Cheating agents :
Definition – These are the drugs used to prevent heavy metal
poisoning.
The process by which these organic compounds combine with
the metals to form relatively stable nonionised ring complexes is
called chelation (chele-clow).
The compound known as chelating agent.


5. Mechanism of Action :
Drug + Metallic ions → Non toxic , water
soluble complex -------eliminated by the kidney.

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

7. EDTA :
Types- sodium EDTA, calcium EDTA.
Calcium sodium has high affinity for lead while disodium salts
exihibits a high affinity for calcium.
Also has affinity for other metals like Pb,Zn,Cd,Cu,radioactive
metals. It can remove from the body by exchanging with calcium
held by it.
Pharmacokinetic ---
Absorption – poorly by GIT. Given by i.v
 i.m route is painful.
Excreted within 24 hours,by glomerular filteration,tubular secretion.

8. Adverse effect :
Common – thrombophlebitis
Other– N,V, toxic nephrosis, renal damage.
Disodium salts may cause hypocalcemic tetany due to excessive
chelation of calcium.
Preparation : inj. Calcium edetate 20% w/v diluted in N.S. or 5%
dextrose before iv administration.
Disodium edetate inj. 20ml amp. Contains 3mg of the drug.
Therapeutic uses :
Lead poisoning.
Diagnostic test for lead poisoning.
Treatment of Porphyria.
Poisoning with iron Cd, platineum.

9. Dimercaprol (BAL) :
Synthesizes by Britisher Stocker and Thomson during second
whorld war-II as an antidote to the arsenical war gas as lewisite.
. Oily ,pungent smelling ,viscous liquid.

M.O.A. – two SH group of dimercaprol bind with toxic metal lead
dimercaprol metal complex .
This complex is dissociable .Dissociation occurs in vivo, causing the
release of toxic metal in active form → problematic.
Therefore adjust the dose in such a way that excess amt. of free
drug is always present in the body to bind the free metal released as
a result of dissociation.

10. Advantage :
1.Protects SH enzymes from inactivation by heavy metals
2. Reactivates the inhibited enzyme.
Pharmacokinetic :
Route –i.m. peak plasma level -2hr.
Metabolism-liver ,6-24 hr.
Excretion – urine.
Dose : 50mg/ml(2ml amp.)
Adverse effect :
Burning sensation of mouth , eye. Lacremation, sialorrhoea, paresthesia
of the excremities, ms pain.
Inj. BAL is painful → sterile abscess and drug fever.
Precaution :
Urine should made alkaline during dimercaprol therapy to protect the
kidneys from toxic effects of the released free metals.
Used cautiously in hypertensive individual.

11. Contraindications :
Hepatic damage.
Iron poisonig.
Cadmium poisoning.
Therapeutic uses :
 Acute poisoning – due to arsenic, gold, antimony, bismuth.
For accidental contamination by arsenical vesicants to eye.
As adjuvants to calcium disodium edetate in lead poisoning
Wilsons desease – in pts allergic to penicillamine.

12. Succimer :
Chemical analogue of dimercaprol.
Effective chelator for lead, arsenic, cadmium,
A/E – N , V, diarrhoea, loss of appetite and skin
rash.

13. D-Penicillamine :
Have strong copper chelating property
d-isomer is used b,coz l-isomer produced optic neuritis and
more toxic.
Like dimercaprol ,it inhibit enzymes transeaminase and
desulfhydase .
Pharmacokinetic :
well absorbed, excreted in urine.
Adverse Effect :
1.General toxicity – sore throat, lymphadenopathy, neuritis,
loss of taste sensation.
2.Heamatological toxicity – leucopenia, thrombocytopenia,
agranulocytosis, aplastic anaemia .

14. Renal toxicity – proteinuria, reversible nephrotic syndrome,
haematuria.
Autoimmune syndrome – myaesthesia gravis, diabetes,
polymyositis, SLE.
Iron deficiency in children and young women
Pyridoxine deficiency.Dose – 250mg
Therapeutic uses :
Wilsons disease – 1-2mg(base) daily in divided doses.
Rheumatoid arthritis – 125mg daily.
Acute lead and mercury poisoning.
Cystinosis, cystinuria, haemosiderosis.
Primary biliary cirrhosis.
Scleroderma.

15. Trientine :
400-800mg t.d.s. daily before meals.
Effective as penicillamine in reversing the
neurological lesion of wilson disease.
Advantages: less toxic than penicillamine,
cause less iron deficiency.

16. Deferiprone :
New,orally effective iron chelator.
Use :
Acute iron poisoning
Iron load condition like cirrhosis of liver.
Dose – tab. 250mg- 500mg
Adverse effect :
Anorexia
Altered taste
Joint pain
Agranulocytosis
Neuropenia

17. Summary :
These are the drugs used to prevent heavy
metal poisoning. Have ability to form
complexes with important biological
radicals like sulfhydryl hydroxyl,
carboxyl, the amino acid, the imidazole.

18. BIBLIOGRAPHY
1. Essential Of Medical Pharmacology- K.D.THRIPATHI 6
th
Edition.
2.The Pharmacology Basis Of Therapeutics -GOODMAN & GILMAN”S 11
th

Edition.
3.Pharmacology and Pharmacotherapeutics- R.S.SATOSKAR. 18
th
Edition
4.Basic & clinical Pharmacology-BARTUM G.Katzung 9
th
Edition

19. 
Thank you