heavy metal poisoning including various metals its side effects, causes of exposure and followed by treatment patterns

1. Heavy Metal
Poisoning
By
Koppala RVS Chaitanya
Department of Pharmacology

2. What is the treatment of poison?
The treatment of toxic symptoms arising due to the overdose of any drug primarily involves the
maintenance of respiration and cardiovascular function. Measures should also be taken to treat
imbalances in fluid and electrolyte levels.
Antidote therapy plays an important role in the management of poisoning. Unfortunately, it does
not give positive results in the treatment of all poisoning cases. Hence, besides antidote
treatment, supportive therapy is also utilized in the treatment of poisoning cases. It includes,
(a) Vomiting: If the poisoning occurs due to an orally ingested substance, a logical
approach is to clear off that substance from the stomach. Vomiting is generally induced
by either taking syrup of ipecac or by injecting apomorphine, 0.066 mg/kg
subcutaneously. In absence of emetics, vomiting can be induced mechanically by
stroking the posterior pharynx. For prompt emesis, it is better to take 1-2 glasses of water
before hand. Emesis is contraindicated if corrosives, strychnine, and petroleum distillates
are ingested during coma.
(b) Gastric Lavage: It is used in cases where emesis does not work. It involves the insertion
of a tube into the stomach of the patient and washing the stomach to remove the
unabsorbed poison. The oral passage is easier but in adults, the nasal route may also be
utilized. The fluid generally used for lavage may be water, normal saline, or one-half
saline solution. The process is effective as long as six hours after the ingestion of poison
and should be repeated until the washing comes free from poison.
(c) Chemical Adsorption: Once the poison has been removed maximally from the stomach
by emesis, the traces of poison left in the stomach can be removed by using activated
charcoal. It easily adsorbs the drug to the surface in an irreversible fashion, thereby
preventing its further absorption and poisoning. It is administered usually as slurry,
suspended in water. It may either be given orally or by lavage. The amount of activated
charcoal to be used is determined in such a way as to achieve a charcoal: drug ratio of
10:1.
(d) Purgation: An aim of every therapy used in the treatment of poisoning is to neutralize or
reduce the manifestations arising due to such poisoning. Purgatives are also employed to
reduce the absorption of the poison by hastening its passage through GIT. Saline
cathartics are usually preferred due to their prompt action and fewer side effects
(e) Forced Diuresis: To treat barbiturates and other intoxications, other options are also
open. These include forced osmotic diuresis and alkalinization of the urine.

3. (f) Antagonism: The drugs having the capacity to block the action of the poison can be
utilized. Such drugs are known as antidotes. They are broadly divided into categories
based on their mechanism of action.
 Some antidotes have an opposite physical, chemical or pharmacological property to
nullify the effect of the poison. In such cases, the problem arises if the duration of
action of the poison and antidote does not match each other. If the duration of action
of the antidote is more, it may lead to poisoning with the antidote.
 Some antidotes fix up the poison molecules by forming a complex with them. They
are also known as chelating agents. Chelating agents possess a high degree of
selective affinity for certain metallic ions.
 Heavy metals cannot be metabolized in the body. During their stay, they combine
with vital functional groups, necessary for normal physiological functions. The
toxicity arising due to this ligand formation may be dealt with by chelating agents.
Chelating agents can prevent or reverse toxic effects by forming soluble chelates
(complexes) with heavy metals. Thus, they enhance the excretion of the metals.
(g) Dialysis: Peritoneal dialysis and hemodialysis are usually employed techniques in life-
threatening intoxication, in the blood; the poison may bind to several cells and plasma
protein. The rate of elimination of such poison, therefore, is governed by the rate of
dissociation of the poison from its binding sites.
 Hemodialysis (Artificial kidney): It is a much more effective dialyzing technique than
peritoneal dialysis. It can be used to treat intoxication due to barbiturates,
glutethimide, methanol, salicylates, etc. Generally, nephrotoxic agents cannot be
dialyzed.
 Peritoneal dialysis: Though it is less effective than hemodialysis, it is generally used
to enhance the rate of elimination of toxic elements from the body. The poisoning
resulting due to overdoses of many exogenous poisons may be treated using this
technique.
(h) Blood Transfusion: When all the approaches to remove poison from the blood fail then
blood transfusion remains the only solution. Similarly, if hemoglobin is converted to
methemoglobin due to the toxic action of the drug present, the life of the patient comes in
danger. In such cases of methemo-globinemia, the circulating blood has to be replaced.

4. Blood transfusion is an effective therapy to supply normal hemoglobin that can train
oxygen to the tissues at the required level.
Heavy Metal Poisoning
To function in various physiological activities smoothly and in a co-ordinated fashion, several
metals are essential. Depending upon their need, some are required in appreciable quantity
whereas some metals are needed in trace amounts. Due to some reasons, if the concentration of
metals in the biophase exceeds that is required, toxic effects start appearing. These toxic effects
can be accounted for based on the interaction of the metal with specific functional groups
(ligands) on the macromolecules (i.e. enzymes or receptors) in the cells. Due to this interaction,
the macromolecule cannot catalyze the functions, vital to the existence of the cell. Metal
generally interacts with functional groups like amino, carboxyl, phenolic, phosphoric, and
sulfhydryl moieties. The interaction with such vital functional groups (ligands) leads to
disruption of energy production and ion regulation. Adverse reactions of metals are also
reported. For example, heavy metals like cadmium, lead, mercury, arsenic, tin, and cobalt can
lead to immunosuppressive effects. Similarly arsenic, chromium, and nickel may cause cancer in
humans.
In the treatment of intoxication due to heavy metals, chelating agents play a dominating role. All
such compounds that can form complexes (chelates) with heavy metals and have a common
property to prevent or reverse the binding of metallic cations to body ligands are collectively
referred to under the term, chelating agents. Chelating agents generally consist of N, O, or S as
ligand atoms. The ligand atoms entrap the metal ion and form a complex with it by co-ordinate
bonds. The bond is often indicated by an arrow. The head of an arrow is directed away from the
atom (ligand) which donates the electron pair needed for the formation of the bond. The stability
of the chelate (complex) formed varies with the metal and ligand atoms. A large number of drugs
can form metal chelates. A chelate formation may be a part of their mechanism of action against
the diseases for which they are intended.
(a) Arsenic Poisoning: Arsenic as such is not needed for the body. It does not catalyze any
biological function. It is the trioxide form, in which arsenic is usually present. The most severe
form of arsenic toxicity involves erythrocyte hemolysis. Similarly, kidney and liver damage may
occur. Dimercaprol, a chelating agent, may be used in the treatment of arsenic poisoning.
In toxic symptoms, arsenic can cause uncoupling of mitochondrial oxidative phosphorylation.
This uncoupling is known as aminolysis, Since it inhibits the functioning of many vital enzymes,
almost every important organ is affected by arsenic poisoning. Besides dimercaprol, oral
penicillamine may also be given to treat the poisoning. But to treat severe arsenic-induced
nephropathy, renal dialysis is the only solution.

5. The most deadly form of arsenic is arsine gas (AsH3). Arsenic exists in three metallic forms:
alpha (α) (yellow), beta (β) (black), and gamma (γ) (grey). Arsenic interferes with cellular
respiration by combining with the sulfhydryl groups of mitochondrial enzymes. It interferes with
glycolysis. Within 30 minutes of exposure, there is a metallic taste in the mouth with a slight
odor of garlic on the breath. Sources of toxicity include tobacco, seafood, environmental (found
in insect poisons), skin contact (some linseed oils), and drinking water. Toxicity symptoms
include nausea, vomiting, abdominal pain, excessive salivation, diarrhea, headache, kidney
failure, muscle paralysis, progressive blindness, and mental impairment.
The common laboratory tests include tissue examination (arsenic deposits mainly in nails and
hair), blood analysis (to check serum arsenic levels), and urine spot test (using chelating agents
like EDTA). Normally, the blood levels of arsenic should be less than 50 micrograms per liter. In
poisoning cases, it may go to several hundred micrograms per liter. In acute poisoning, an ECG
can reveal arrhythmias. A plain abdominal X-ray may show opacities in the stomach due to the
presence of arsenic
The first step in treating any heavy metal toxicity is to identify the toxic element and begin its
removal process. The important steps of the therapy are:
 Gastric lavage.
 Hemodialysis and chelation therapy to remove arsenic.
 Multiple transfusions to compensate for blood and fluid loss.
 Intravenous Vitamin C and replacement of mineral infusions are also recommended to
support the body during the metal removal process.
 Dimercaprol is used as chelating agent.
 Analgesics may be used to suppress pain
(b) Mercury Poisoning: Mercury constitutes an important part of the chemical structure of
many diuretics, antiseptics, antibacterials, and laxatives. It has a high affinity for sulfur. Hence
mercury readily forms covalent bonds with sulfhydryl groups and inactivates the enzymes
containing the sulfhydryl group. Thus, the presence of mercury can easily retard normal cell
metabolism.
Dimercaprol and penicillamine which contain a sulfhydryl group can be routinely used to treat
intoxication due to either inorganic or elemental mercury. N-acetyl-D and L-penicillamine
appear to be more potent and safer than the former agents. In severe cases, hemodialysis may
also be employed.
Mercury poisoning (mercurialism) occurs due to the exposure of the patient to mercury (in its
elemental form), inorganic mercury salts, or organomercury compounds. The sources of
exposure include ingestion of contaminated food and water, breathing contaminated air,

6. industrial sources (mercury mining and smelting), organic mercurial pesticides, crematoriums,
waste incinerators, and volcanoes.
Mercury damages gums, teeth, mouth, endocrine system, kidneys, and CNS. Mercury inhibits the
formation of myelin (nerve sheath) accounting for neurological consequences. Mercury
inactivates S-adenosyl methionine required with catechol-o-methyl transferase to metabolize
noradrenaline-like catecholamines. This leads to symptoms of sympathetic nervous system
stimulation like profuse sweating, tachycardia, hypersalivation, and hypertension. Other
symptoms like metallic taste, tumors, skin discoloration (pink cheeks, fingertips, and toes),
edema, and burning or itching may also be seen.
The therapy of mercury poisoning includes:
 Administration of chelating agents like sodium salt of DMPS (2, 3-mercapto-1- propane
sulfonic acid).
 Intravenous vitamin C supports the body during the metal removal process.
 D-penicillamine, dimercaprol, and calcium disodium edetate are examples of some
effective antidotes to treat systemic heavy metal poisoning.
Sources of sulfur such as lipoic acid and garlic are useful in mercury toxicity.
(c) Lead Poisoning: Human exposure to lead is primarily from food, environmental and
industrial sources. It is mainly absorbed into the circulation of GIT and the respiratory system. In
the body lead is mainly deposited in the liver, kidney, and bones. Chronic exposure to lead
results in gastrointestinal, neuromuscular, CNS, hematological and renal toxicities.
Lead as such is not essential for life. The intoxication of lead can be treated by using one of the
three chelating agents: Edetate calcium disodium (CaNa2 EDTA), dimercaprol, and D-
penicillamine. The lead-EDTA complex is non-toxic and water-soluble and hence is rapidly
excreted. Usually, at the start, the combination of edetate calcium disodium and dimercaprol is
used. This is followed by oral penicillamine, which continued for a long term.
Lead accumulates slowly in the body and even at low doses, it may lead to poisoning. The major
fraction of lead gets deposited in the bones and teeth while in blood, it accumulates with
erythrocytes. Plain X-ray may show transverse lines in tubular bones suggesting arrested bone
growth due to prolonged lead exposure, X-ray fluorescence is a sensitive method of detecting
low levels of lead in the body.
Lead interacts with sulfhydryl groups and interferes with the action of enzymes necessary for
haem synthesis, hemoglobin, and cytochrome production. It causes hemolysis. Toxicity
symptoms include nausea, constipation, headache, hemolytic anemia, fatigue, mania,
convulsions, renal impairment, and hypertension.

7. The blood level of lead should be less than 100 mcg/L. The toxicity symptoms start appearing
when it goes in the range of 500 − 100 mcg/L.
The important steps of therapy include:
 The intravenous drip of normal saline with or without parenteral chelating agents
(calcium disodium edetate).
 Orogastric or nasogastric catheter and irrigation with polyethylene glycol.
 Management of seizures and coma.
Chelation therapy should be gradually withdrawn:
 To avoid metal leaking out of bones leading to a rebound rise in blood levels. patients
otherwise may develop hypertension, raised intracranial pressure, and renal failure due to
chelated lead compounds.
(d) Cadmium Poisoning: It occurs in nature in association with zinc and lead. After
absorption, the kidney retains a higher concentration of cadmium than any other tissue. This
accumulation leads to renal tubular damage. The liver also shoulders considerable deposition of
cadmium.
Intoxication leads to nausea, dizziness, diarrhea, chest pain, and irritation of the upper respiratory
tract. Treatment commences with respiratory support and steroidal therapy. A chelating agent
like edetate calcium disodium can be used whereas; dimercaprol should not be used, due to its
nephrotoxicity. Vitamin D is recommended for the treatment of associated orthopedic problems.
(e) Iron Poisoning: The body has a considerable amount of iron, circulating in the plasma. The
plasma circulating iron cannot exhibit toxic reactions because of the presence of a natural
chelating, agent, transferrin in the blood. It protects the body from the toxic actions of the
circulating iron. Iron, if absorbed into circulation in excess amounts, may lead to toxic
manifestations. These include irritation of GIT, pneumonitis, convulsions, and coma. Hepatic
damage is also reported to occur.
Deferoxamine is an effective chelating agent in treating systemic iron toxicity.
(f) Cyanide Poisoning: Even though cyanide does not come under the term “heavy metals”,
the treatment of cyanide poisoning deserves special attention. Cyanogenic compounds if ingested
orally, may release hydrogen cyanide due to their hydrolysis in GIT. The cyanide ion impairs
several vital cellular functions. For example, there occurs impairment of tissue oxygen utilization
due to inhibition of the cytochrome oxidase enzyme. The blood runs deficient in oxygen. The
patient suffers from hypoxia followed by ataxia, coma, and death.
There is a need for two-fold therapy in the treatment of cyanide poisoning. i.e., (1) the cyanide
ions present in the circulation should immediately be converted into a nontoxic form, and (2)

8. attempts should be made to reverse the condition of hypoxia i.e. placing the patient in the
oxygen-riched atmosphere and a quick conversion of methemoglobin to hemoglobin should be
effected. The treatment involves the use of amyl nitrite by inhalation or sodium nitrite by
injection. These agents serve the second purpose. The subsequent intravenous administration of
sodium thiosulfate facilitates the conversion of free cyanide ions to nontoxic thiocyanate form.
Thiocyanate can readily be excreted in the urine.