CHELATORS AND HEAVY METALS

TERMS
Chelating agent

erethism

pica

Plumbism

Definition
A molecule with two or more
electronegative groups that can form
stable coordinate complexs with
multivalent cationic metal atoms
Syndrome resulting from mercury
poisoning characterized by INSOMIA,
MEMORY LOSS, EXCITABILITY, and
DELIRIUM
Ingestion of nonfood substances; pica
also refers to ingestion of lead-based
paint fragments by small children
Range of toxin syndromes due to chronic
lead poisoning that may vary as a
function of blood or tissue levels and
patient age

CHELATORS
A. Dimercaprol: bidentate chelator
a. Clinical use: for acute arsenic and mercury poisoning. For lead
poisoning in conjunction with edentate. Given parenterally
b. Toxicity: very lipophilic, readily enters cells. Toxicity includes transient
hypertension, tachycardia, headache, nausea, vomiting, paresthesia,
and fever.
B. Succimer: bidentate chelator
a. Clinical use: for lead toxicity. For arsenic, mercury poisoning
b. Toxicity: GIT distress, CNS effect, skin rash, elevation of liver enzymes.
Should not be administered with other chelating drugs
C. Penicillamine: bidentate chelator
a. Clinical use: for treatment of copper poisoning and Wilsons disease.
For gold, arsenic, lead intoxication, rheumatoid arthritis.
b. Toxicity: nephrotoxic
D. Edentate (EDTA): polydentate chelator
a. Clinical use: for lead poisoning. Given as calcium disodium salt
b. Toxicity: nephrotoxic. Risk can be reduced by adequate hydration and
restricting treatment to 5 days
E. Deferoxamine: polydentate chelator. Competes with heme in hemoglobin ad
cytochrome

a. Clinical use: for acute iron intoxication

b. Toxicity: skin reactions, neurotoxic, hepatic and renal dysfunction.
TOXICOLOGY OF HEAVY METALS
A. Lead: no useful purpose in the body. Present in air and water.
a. Acute lead poisoning: primary signs are acute abdominal colic and CN
changes. In children, may take form of acute encephalopathy.
b. Chronic lead poisoning (plumbism). Signs include peripheral
neuropathy, anorexia, tremor, GIT symptoms. Treatment includes
removal from the sources of exposure and chelation therapy usually
with edentate, demercaprol or penicillamine
c. Organic lead poisoing: due tetraethyl lead or tetramethyl lead
antinonck gasoline additives. Primary signs are in the CNS that
includes hallucinations, headache, irritability, convulsions, and coma.
Treatment consists of decontamination and seizure control.
B. Arsenic: released during burning of coal. Known human carcinogen.
a. Acute arsenic poisoning: results in severe GIT discomfort, vomiting,
rice-water stools. A sweet, garlicky odor may be detected in the breath
and stools. Treatment consists of supportive therapy to replace water
and electrolytes and chelation therapy with dimercaprol.
b. Chronic arsenic poisoning: manifested by skin changes, hair loss, bone
marrow depression and anemia, and chronic nausea and GIT
disturbances. Treatment includes dimercaprol.
c. Arsine gas: used in semiconductor industry. Signs include massive
hemolysis. Treatment is supportive.
C. Mercury
a. Acute mercury poisoning: occurs through inhalation of inorganic
elemental mercury. Causes chest pain, shortness of breath, nausea,
and vomiting, kidney damage, CNS damage. Treatment includes
dimercaprol.
b. Chronic mercury poisoning: syndrome involving the gums ad teeth, GIT
disturbances, and neurologic and behavioral changes. Treatment with
penicillamine and dimercaprol.
c. Organic mercury poisoning
D. Iron: Acute poisoning from ingestion of ferrous sulfate tablets occurs in
children. Initial symptoms include vomiting, GIT bleeding, lethargy, gray
cyanosis. Followed by signs of severe GIT necrosis, jaundice, seizures, and
coma. Deferoxamine is the chelating agent of choice.

metal

Form of
entering

Route of
absorption

Lead

Inorganic lead
oxides and
salts

GIT,
respiratory,
skin

Tetraethyl lead

Skin, GIT

Inorganic
arsenic salts

All mucosal
surfaces

Arsine gas

Inhalation

Elemental

Inhalation

Erythrocytes
CNS, kidneys

Inorganic salts

GIT

Kidneys, GIT

Penicillamine,
dimercaprol

Organic
mercurials
Ferrous sulfate

GIT

CNS

Supportive

GIT

GIT, CNS,
blood

deferoxamine

Arsenic

Mercury

Iron

Target
organs for
toxicity
Hematopoietic
system, CNS,
kidneys

Treatment

CNS

Seizure
control,
supportive
Dimercaprol,
succimer,
penicillamine

Capillaries,
GIT,
hematopoietic

Dimercaprol,
edentate,
penicillamin,
succimer

Supportive
Dimercaprol