This document discusses toxicities and management of poisonings due to heavy metals such as lead, mercury, arsenic, and iron. It provides details on the symptoms of poisoning from each metal, as well as common chelation therapies used to treat heavy metal poisoning, including dimercaprol, calcium disodium edetate, penicillamine, deferoxamine, and deferiprone. The document emphasizes that heavy metal poisoning can be acute or chronic and the metals may enter the body through ingestion, inhalation, or absorption through skin or mucous membranes.

1. Toxicities and management of
poisonings due to Heavy Metals
(Pb, Hg, As, Fe)
Dr. S. Parasuraman, M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy
AIMST University
Lead Mercury
IronArsenic

2. Heavy Metals poisoning
• Heavy metals are commonly defined as those elements with a high
(>5.0) relative density.
• Heavy metals are potential to cause environmental or human
toxicity.
• Heavy metal poisoning can be acute or chronic and may be caused
by the following:
– Lead, Mercury, Iron, Arsenic
– Cadmium, Thallium, Bismuth
• The metals may enter the body by:
– Ingestion
– Inhalation
– Absorption through the skin or mucous membranes

3. Heavy Metals poisoning
• The most common cause of heavy metal poisoning is lead.
Lead poisoning is most common in affluent countries, due to
removal of lead from paint, petrol and food cans.
• Mercury can be found in the elemental state (dental
amalgam, thermometers), inorganic (industrial processes) and
organic compounds (pesticides, wood preservatives, some
medicines, and contaminated fish). Ingestion of disc batteries
by children can also lead to heavy metal poisoning amongst
other problems.
• Poisoning from other heavy metals most often occurs in
individuals regularly exposed to the metals in their work
environment.

5. Lead poisoning
• Age-dependent differences in the absorption
• Adult absorb 10% of an ingested dose. Children- 40%
• Initially distributed to the soft tissues and slowly redistributed to
bone, teeth and hair
• Detected by x-ray
• Half-life: 1-2 months in blood; 20-30 yr bone.
– CNS: headache, confusion, clumsiness, insomnia, fatigue, impaired
concentration. Disease progresses, colonic convulsions and coma can
occur. Treated with chelation therapy. Blood lead levels 5-20 μg/dL in
children have lower IQ levels.
– GIT: Discomfort, constipation. Higher exposures can produce painful
intestinal spasms.
– Blood: Hypochromic and microcytic anemia results shortened
erythrocyte. Inhibit the heme synthesis enzymes.

6. Mercury poisoning
• Toxic exposures to elemental mercury (inhaled) causes tremors,
depression, memory loss, decreased verbal skills and inflammation of the
kidneys. High concentrations of elemental mercury cause nonselective
pulmonary toxicity.
• Exposures to inorganic salts of mercury (mercuric chloride) lead to renal
damage. Hazardous exposures of the public to inorganic forms of mercury
are uncommon.
• Consumption of food substances contaminated with methylmercury (fish)
cause organic mercury toxicity. Symptoms of high levels of organic
mercury toxic can appear several days to several weeks after ingestion.
Symptoms include visual disturbances, paresthesias, ataxia, hearing loss,
mental deterioration, muscle tremors, movement disorders. With sever
exposure cause paralysis and death.

7. Arsenic poisoning
• Symptoms of arsenic poisoning begin with headaches, confusion, severe
diarrhea, and drowsiness.
• As the poisoning develops, convulsions and changes in fingernail
pigmentation called leukonychia may occur.
• Chronic exposure: vitamin A deficiency ---> heart disease, night blindness
37 million people in more than
70 countries are probably
affected by arsenic poisoning
from drinking water

8. Iron poisoning
• Iron is a vital mineral in the human body.
• Iron toxicity cases hemosiderosis and hemochromatosis.
• Iron toxic serum level: Mild toxicity: 450-500μg/dl; sever toxicity: 800-
1000 μg/dl.
• Toxic effect due to hemorrhagic necrosis in GIT

9. Treatment for heavy metal poisoning
• Chelation Therapy
– Chelation agent + Metal = Chelate
– A chelating agent is chemical compound or drug molecule
capable of forming a heterocyclic ring with a metal ion as
its closing member.

10. Common antidotes
Poison Antidotes
Lead Dimercapto succinic acid
Lead Calcium disodium edetate
Mercury
Arsenic
Gold
Dimercaprol
Iron Deferoxamine
Deferiprone
Copper/ mercury Penicillamine
Cyanide Sodium nitrite
Sodium thiosulfate
Amyl nitrite pearls

11. HS OH
SH
M+
S
S
OH
MDimercaprol
M+
EDTA
D-Penicillamine

12. Dimercaprol
• Dimercaprol/ British Anti Lewisite/ BAL (Oily nature)
• SH group of dimercaprol bind with heavy metal and form sulfhydryl
complex
• Two molecule of dimercaprol with one metal ion is more stable than 1:1
complex.
• Dimercaprol produce dose dependent toxicity (large amount should not
be given)
• It’s a narrow therapeutic agent and produce serious side effects includes
nephrotoxicity and hypertension.
• Used for Heavy metal (As, Hg, Au, Bi, Ni and Sb) poisoning and Wilson's
disease (autosomal recessive genetic disorder in which copper
accumulates in tissues).
• Dimercaprol metabolized in liver by glucuronide conjugation and excreted
in 4-6 h.
• Dimercaprol-metal complex dissociated faster in acidic urine and the
release metal can damage kidney.

13. Dimercaprol
• Adverse effects:
– Rise in BP, tachycardia, vomiting, tingling and burning sensations,
inflammation of mucous membranes, sweating, cramps, headache and
anxiety.
– Antihistaminics given 30 min before dimercaprol injection to reduce
intensity of adverse effects.
Dimercaptosuccinic acid
• Similar to dimercaprol in chelating properties, water soluble,
less toxic and orally effective.
• Side effects: Nausea, anorexia and loose motions.
Cont.,

14. Calcium disodium edetate
• Calcium chelate of Na2 EDT A.
• higher affinity with Pb, Zn, Cd, Mn and Cu and some
radioactive material.
• Not ionized in G.I.T. administered i.v route.
• Brain and CSF: Not cross BBB.
• Use:
– Lead poisoning- 1 gm is diluted to 200- 300 ml in saline or glucose
solution and infused i.v. over 1 hour twice daily for 3-5 days.
• Adverse effects:
– Relatively safe.
– Kidney damage with proximal tubular necrosis is the most important
problem.
– Anaphylactoid reaction with fall in BP.

15. Penicillamine
• Product of penicillin.
• d-isomer is active heavy metals. l-isomer produce optic
neuritis and are more toxic.
• Use:
Used for the treatment of
– Wilson's disease (genetic disorder, copper accumulates in tissues).
– Chronic lead poisoning.
– Copper/mercury poisoning.
– Cystinuria and cystine stones.
• Adverse effects
– Short-term administration: Safe.
– Long-term use: Dermatological, renal, haematological and collagent
issue toxicities.

16. Desferrioxamine
• High affinity with iron
• One gram capable of chelating 85 mg of elemental iron
• Stable nontoxic complex - excreted in urine.
• Route of administration:
– Oral absorption: poor
– Parenteral: preferable
• Use:
– Acute iron poisoning (for children)
– Transfusion siderosis
• Adverse effects
– Cause histamine release
– abdominal pain, loose motions, muscle cramps, fever and dysuria

17. Deferiprone
• Orally active iron chelator
• Treatment of transfusion siderosis in thalassemia patients.
• Iron chelator used to clear iron overload.
• Side effects
– Anorexia, vomiting, altered taste, joint pain, reversible neutropenia,
rarely agranulocytosis