1. Heavy Metals toxicity

2. Heavy Metals
The most common heavy metals lead, arsenic, mercury, and iron—frequently cause toxicity in humans.
The toxicity profiles of metals differ, but most of their effects appear to result from interaction with sulfhydryl groups of enzymes and regulatory proteins.

3. Heavy metal and Chelators
Dimercaprol
lead
Iron
Succimer
Deferoxamine
Unithiol
Penicillamine
arsenic
Mercury
EDTA

4. Lead Acute Lead Poisoning
occur rarely from industrial exposures (usually via the inhalation of dust)
in children who have ingested large quantities of chips or flakes from surfaces in older houses covered with lead-containing paint.
The primary signs of this syndrome are acute abdominal colic and central nervous system (CNS) changes, including, acute encephalopathy.
The mortality rate is high with lead encephalopathy, and prompt chelation therapy is mandatory.

5. Lead Chronic Lead Poisoning
Also called (plumbism) is much more common than the acute form.
Signs include peripheral neuropathy (wrist-drop is characteristic), anorexia, anemia, tremor, weight loss, and gastrointestinal symptoms.
Treatment involves removal from the source of exposure, and chelation therapy, usually with oral succimer in outpatients and with parenteral agents (eg, EDTA with or without dimercaprol) in more severe cases.
Chronic lead poisoning in children presents as growth retardation, neurocognitive deficits.

6. Arsenic
an environmental pollutant released during the burning of coal.
Acute arsenic poisoning results in severe GIT discomfort, vomiting, "rice-water" stools, with dehydration and shock.
A sweet, garlicky odor may be detected in the breath and the stools. Treatment consists of supportive therapy to replace water and electrolytes, and chelation therapy with dimercaprol.

7. Arsenic
Chronic arsenic intoxication causes skin changes, hair loss, bone marrow depression and anemia
Dimercaprol therapy appears to be of value.
Arsine gas (AsH3), an occupational hazard, is used in the semiconductor industry.
Arsine causes a unique form of toxicity characterized by massive hemolysis. Pigment overload from erythrocyte breakdown can cause renal failure. Treatment is supportive.

8. Mercury
The main source of inorganic mercury as a toxic hazard is through the use of mercury-containing materials in dental laboratories , insecticides, and batteries.
Organic mercury compounds are used as seed dressings (treatments to prevent fungal and bacterial infection of seed and to improve the seed's dispersion and adhesiveness) and fungicides.

9. Mercury
Acute mercury poisoning occurs through inhalation of inorganic mercury.
causes chest pain, shortness of breath, nausea and vomiting, kidney damage, gastroenteritis, and CNS damage.
Acute ingestion of mercuric chloride causes a severe, life-threatening hemorrhagic gastroenteritis followed by renal failure.
Chronic mercury poisoning may occur with inorganic or organic mercury. Poisoning from inhalation of mercury vapor presents as a diffuse set of symptoms involving the gums and teeth, gastrointestinal disturbances, and neurologic and behavioral changes (erethism).

10. Iron
Acute poisoning from the ingestion of ferrous sulfate tablets occurs frequently in small children
The initial symptoms of iron poisoning include vomiting, gastrointestinal bleeding, lethargy, and gray cyanosis.
These can be followed by signs of severe gastrointestinal necrosis, pneumonitis, jaundice, seizures, and coma.
Deferoxamine is the chelating agent of choice.

11. Chelators
are organic compounds with 2 or more electronegative groups that form stable bonds with cationic metal atoms.
These stable complexes lack the toxicity of the free metals and often are excreted readily.
Chelators, which function as chemical antagonists, are used as antidotes in the treatment of heavy metal poisoning.

12. Chelators
Chelators used clinically include dimercaprol (BAL), succimer, unithiol, penicillamine, edetate (EDTA), and deferoxamine.
1- Dimercaprol
Dimercaprol is used in acute arsenic and mercury poisoning and, in combination with EDTA, for lead poisoning. It is an oily liquid that must be given parenterally.

13. Chelators
2- Succimer
Succimer (DMSA) is a water-soluble bidentate congener of dimercaprol.
used for the oral treatment of lead toxicity in children and adults. It is as effective as parenteral EDTA in reducing blood lead concentration. Succimer is also effective in arsenic and mercury poisoning, if given within a few hours of exposure.
3- Unithiol
A water-soluble derivative of dimercaprol, unithiol can be administered orally or intravenously.
Intravenous unithiol is used in the initial treatment of severe acute poisoning by inorganic mercury or arsenic.

14. Congener 4- Penicillamine
Penicillamine, a derivative of penicillin, is another bidentate chelator.
The major uses of penicillamine are in the treatment of copper poisoning.
It is sometimes used as adjunctive therapy in gold, arsenic, and lead intoxication and in rheumatoid arthritis. The agent is water-soluble, well absorbed from the gastrointestinal tract, and excreted unchanged.

15. 5- Ethylenediaminetetraacetic acid
(EDTA) (edetate) is an efficient polydentate chelator of many divalent cations, including calcium, and trivalent cations.
The primary use of EDTA is in the treatment of lead poisoning. Because the agent is highly polar, it is given parenterally. To prevent dangerous hypocalcemia, EDTA is usually given as the calcium disodium salt.
6- Deferoxamine
Deferoxamine is a polydentate bacterial product that has an extremely high and selective affinity for iron.
Fortunately, the drug competes poorly for heme iron in hemoglobin and cytochromes.
Deferoxamine is used parenterally in the treatment of acute iron intoxication and in the treatment of iron overload caused by blood transfusions in patients with diseases such as thalassemia

16. Thank you