The document discusses heavy metals, their sources, and the harmful effects they have on human health, including organ damage, oxidative stress, and carcinogenic properties. It details various chelating agents used to detoxify the body from heavy metals, their mechanisms, routes of administration, and side effects. Notable chelates include dimercaprol, penicillamine, and EDTA, each with specific applications, advantages, and contraindications.

1. z
CHELATING AGENTS

2. Heavy Metals – what are they
and where do they come from
Lead – petrol, paint, batteries.
Mercury – fillings in teeth, fish, paint,
Cadmium – Cigarettes, tyres, metal platings.
Arsenic-Pesticides,chickenfeeds,rice
2

3. Heavy Metals – what are they
and where do they come from
 Aluminum – Cooking wares, aluminum foil, antacids, canned
drinks/foods
 Antimony – Carpets, flame retardant clothes
 Iron
 Copper
3

4. z
 Organic lead
 =tetra ethyl/methyl lead as anti knock agent, absorbe
skin/inhalation
 Organic Hg poisoning –epidemic in minamata village(
mercury)fish consumption in minamata bay with efflue
plastic manufacturing industry in japan

5. z
 Mercury
- Bleaching agents 25%
- Electrical equipments 20%
- Paints 15%
- Thermometers 10%
- Diagnosis on urine Hg levels

6. z

7. z
What are the effects of these
metals ove
 They are oxidised to form free radicals resulting in the
destruction of cells,
 They affect organs inhibit the proper functioning of ce
contribute to gastrointestinal problems,
 Interfere with enzyme systems.
 Weaken the immune system.
 They are carcinogenic.
7

8. z
Mechanism of
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

9. z
Chelating agents forms
complexes with heavy metals
Stable Chelates
Nontoxic, Easily excreted
( Greek Chele – the compound that holds metal like a
)

10. z
Individual a
 Dimercaprol
 Succimer
 Unithiol (DMPS)
 Trientine
 Penicillamine
 EDTA -Ethylene diamine tetra acetic acid
 Deferoxamine
 Deferiprone

11. z
1. DMSA(di mercapto succinic acid)
2. DMPS(di mercapto propane sulfonic acid)
3. DTPA= diethylene triamine penta acetic acid –remo
Uranium& Plutonium

12. z
Intramuscular/Intravenous
 Dimercaprol
 EDTA
 Desferroxamine
ORAL
 Succeimer
 D-penicillamine
 Trientine
 Deferiprone

13. z
Other Heavy Metal Detox O
 Reduced Glutathione
 Alpha Lipoic Acid
 N-Acteyl Cysteine
 TTFD Transdermal Allithiamine-ACTIVE-B1
 Transdermal DMPS
 Transdermal DMSA
13

14. z
Dimercapro
 Developed during world war II as an antidote to nerve gas
Lewisite.
 Used in poisoning by Arsenic, lead, mercury, gold
 Oily fluid, pungent odour, unstable hence peanut oil is
employed as solvent

15. z
 Forms chelation complex between its sulfhydryl groups and
heavy metal, and excreted.
 High incidence of S/E- hypertension, tachycardia, nausea,
headache, salivation, lacrimation, pain at injection site.
 Nephrotoxic,
- Regimen is designed to maintain plasma BAL
adequate to form 2:1 BAL-metal complex
 - Alkalization of urine protect kidney. Urine alkalisation
prevent reabsorption of Hg, As

16. z
 Cant be given orally
 Deep IM 100 mg/ml sol. in peanut oil, peak reaches in 30-60
min, excreted in 4 hrs.
 In Arsenic poisoning 3-4 mg/kg IM 4-12 hrly till abdominal
symptoms subside
 C/I- G-6-PD patients, hepatic insufficiency,
Iron and cadmium poisoning
BAL- Fe complex is toxic

17. z
British anti-l
 New congenors:
 DMSA (di mercapto succinic acid)
 DMPS (di mercapto propane sulfon
 Advantages over BAL
 More polar-confined to ECF
 Less cell toxicity
 Orally given
 Used in children –for lead poisoning, arsenic ,Hg. Po
 Prevent kidney stones in cystinuria

18. z
Penicill
 Initially from urine of pts receiving penicillin, but now synthetic
 Useful in copper,
 mercury, zinc, lead toxicity as well as rheumatoid
arthritis.
 Well absorbed orally, peak in 1-3 hrs
Food, antacids, iron reduce its absorption.

19. z
 For chelation, 1-1.5 g/day in 4 divided doses
 In wilsons disease, 1-2 g/day in 4 doses, Monitor urin
levels
 In Rh. Arthritis, 125-250 mg OD, titrate according to r
 Experimental uses – in biliary cirrhosis, scleroderma,
effects on immunoglobulins and immune complexes

20. z
 S/E- Rash, urticaria, maculopapular lesions
Leucopenia, aplastic anemia
Proteinuria, hematuria
C/I- Pregnancy
Renal insufficiency
Bone marrow failure
 N-acetyl penicillamine more effective in Hg poisoning
 It is not used in penicillin allergic Pts

21. z
tri
 Tri ethylene tetra amine HCL GIVEN IN E
stomach
 Mainly excreted unchanged in urine
 Alkalanise urine to prevent kidney damag
 C/I- iron, cadmium, Selenium, tellurium =
toxicity, give anti histaminics 30 min befor

22. z
Tri
 Useful in pt’s of wilsons disease. Cupviuretic (copper)
 Orally effective, 2 gm daily in 4 divided doses for adults and
1,5 gm for children
 Less S/E than penicillamine
 Iron deficiency occur( iron supplementation with 2 hours
spacing)
 Trientene also for nickel toxicity

23. z
 NOT USEFUL in Mercury poisoning because,
- Hg tightly bound to sulfhydryl groups
- Sequestrated in body compartment not
penetrated by EDTA
 Sodium edetate useful in emergency treatment of
hypercalcaemia

24. z
 Excreted in urine, KFT testing is a MUST.
 S/E- Hypocalcemic tetany, malaise, fever, fatigue
 Mainly affects kidneys, especially PCT

25. z
Deferox
 Obtained from Actinomycete Streptomyces pilosus
 Removes iron from hemosiderin, ferritin but not from
hemoglobin and cytochromes.
 Not absorbed orally, hence IM/IV.
 For severe cases, 10-15 mg/kg/hr IV constant infusion, but in
moderate cases, 50 mg/kg IM (max. 1 gm)

26. z
 For chronic cases, 0.5-1.0 gm/day
 Also for chelation of aluminium in dialysis pts.
 S/E- Allergic reactions – rash, anaphylaxis
 Diarrhea, cramps, fever, tachycardia, nephrotoxicity o
term use.