Heavy Metal Toxicity

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Heavy Metal Toxicity
METALS AND DRUGS (CHELATORS)
TO CONSIDER METAL CHELATING AGENTS
(DRUGS) Lead Ethylenediamine-tetraacetic
acid (EDTA) 2,3-dimercatosuccinic acid
(Succimer) 2,3-dimercatopropanol (BAL,
Dimercaprol) Penicillamine Cadmium Ethylened
iamine-tetraacetic acid (EDTA) Mercury N-acetyl
-penicillamine (NAP) Penicillamine 2,3-dimer
catopropanol (BAL, Dimercaprol) 2,3-dimercatosu
ccinic acid (Succimer) Arsenic N-acetyl-penici
llamine (NAP) Antimony Ethylenediamine-tetraa
cetic acid (EDTA) Iron Deferoxamine
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• Environmental Factors That Influence Lead
  Toxicity
• Pollution from air line industry- major cities
  like Atlanta, Chicago, New York
• Pottery related lead toxicity associated with
  travelling
• School Children Projects-associated with handling
  clay
• Consumption of illicitly distilled liquor
• 5. Old lead pipes corrode and contaminate
  drinking water
• Lead contamination associated with painting
• Gasoline tank cleaning associated organic lead
  toxicity
• Recent recalls on toys (Made in China) due to
  excessive lead contamination

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Lead Absorption a. Skin- alkyl lead compounds
(because of lipid solubility) b. Inhalation- up
to 90 depending particle size c. GI- adults 5
t0 10, children 40 Distribution Initially
carried in RBC and distributed to soft tissues
(kidney and liver) redistributed to bone, teeth,
and hair Source of exposure a. GI- paint,
pottery, moonshine b. Inhalation- metal
fumes c. Skin- tetraethyl lead in
gasoline Mechanism of Toxicity a. Inhibits
heme biosynthesis b. Binds to sulfhydryl groups
(-SH groups) of proteins Diagnosis a. History
of exposure b. Whole blood lead level 1.
Children gt25 µg/dl treatments 2. Adults gt50
µg/dl candidates for treatment c. Protoporphyrin
levels in erythrocytes are usually elevated
with lead levelsgt 40 µg/dl d. Urinary lead
excretion gt80 µg/dl e. Urinary d aminolevulonic
acid Treatment a. Remove from exposure b.
CaNa2EDTA c. 2,3-dimercaptopropanol
(Dimercaprol, BAL) d. 2,3-dimercaptosuccinic
acid (Succimer) e. D-penicillamine
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Mercury (Hg) Source of exposure a.
environmental from electronics and plastic
industry b. seed fungicide treatment, dentistry
(dental amalgam fillings), wood preservatives,
herbicides and insecticides, thermometers,
batteries, and other products Absorption a.
GI- inorganic salts are variably absorbed (10)
but may be converted to organic mercury (methyl
and ethyl in the gut by bacteria) organic
compounds are well absorbed gt90 b. Inhalation-
elemental Hg completely absorbed Mechanisms of
toxicity a. dissociation of salts precipitates
proteins and destroys mucosal membranes b.
necrosis of proximal tubular epithelium c.
inhibition of sulfhydryl (-SH) group containing
enzymes Diagnosis a. history of exposure b.
blood mercury Treatment a. remove from
exposure b. Hg and Hg salts gt 4 µg/dl 2,3
dimercaptopropanol (BAL), penicillamine,
N-acetyl-penicillamine (most effective) Minamata
disease
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Arsenic, As3, As5 Sources of exposure a.
GI well water, food b. Inhalation- fumes and
dust from smelting Environmental byproducts
of smelting ore, AsGa in semiconductors,
herbicides and pesticides Absorption a.
GI-inorganic trivalent (arsenites) and
pentavalent (arsenates) salts gt90
organic also bound as tri and pentavalent
gt90 Distribution accumulates in lung, heart,
kidney, liver, muscle and neural tissue.
Concentrates in skin, nails and hair. Half life
is 7 to 10 hours Mechanism of toxicity a.
Membranes protein damage of capillary
endothelium increased vascular permeability
leading to vasodilation and vascular collapse b.
Inhibition of sulfhydryl group containing
enzymes c. Inhibition of anaerobic and oxidative
phosphorylation (substitutes for inorganic
phosphate in synthesis of high-energy
phosphates) Symptoms a. Acute damage to
mucosa, sloughing, diarrhea (rice-water stools),
hypovolemic shock, fever, etc. b. Chronic-
weakness, GI irritation, hepatomegaly, melanosis,
arrhythmias, peripheral neuropathy, perivascular
disease (blackfoot disease) c. Carcinogenicity-
epidemilogic evidence liver angiosarcoma, skin
and lung cancer Treatment a. Remove from
exposure b. Acute supportive therapy- fluid,
electrolyte replacement, blood pressure support
(dopamine) c. Chronic penicillamine w/o
dialysis Arsine gas (AsH3) acts as hemolytic
agent with secondary to renal failure.
Supportive therapy transfusion (chelators have
not been shown to be beneficial)
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METALS AND DRUGS (CHELATORS)
TO CONSIDER METAL CHELATING AGENTS
(DRUGS) Lead Ethylenediamine-tetraacetic
acid (EDTA) 2,3-dimercatosuccinic acid
(Succimer) 2,3-dimercatopropanol (BAL,
Dimercaprol) Penicillamine Cadmium Ethylened
iamine-tetraacetic acid (EDTA) Mercury N-acetyl
-penicillamine (NAP) Penicillamine 2,3-dimer
catopropanol (BAL, Dimercaprol) 2,3-dimercatosu
ccinic acid (Succimer) Arsenic N-acetyl-penici
llamine (NAP) Antimony Ethylenediamine-tetraa
cetic acid (EDTA) Iron Deferoxamine
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• Study Aid For Heavy Metal Toxicity
• Know specific chelating agents for each metals
  and route of administration.
• Lead Calcium disodium EDTA (IV)
• 2, 3-dimercaptosuccinic acid (Succimer) (Oral)
• 2, 3-dimercaptoproponol (BAL, Dimercaprol) (IM)
• Penicillamine (Oral)
• Cadmium Calcium disodium EDTA (IV)
• Mercury 2, 3-dimercaptosuccinic acid (Succimer)
  (Oral)
• 2, 3-dimercaptoproponol (BAL, Dimercaprol)
  (IM)
• Penicillamine (Oral)
• N-acetyl-penicillamine (Oral)
• Arsenic N-acetyl-penicillamine (Oral)
• Penicillamine (Oral)
• Arsine gas (AsH3) (hemolytic agent) transfusion
• Iron Defroxamine (IM, slow IV, Oral-under rare
  circumstance)
• Know the mechanism of absorption.
• Skin, Inhalation, GI
• Know the mechanisms of toxicity