Arsenic Poisoning

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Arsenic Poisoning

• Tawnee Boudreau, Ryan McGuire, and Karly Steinhoff

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Arsenic

• Naturally occurring semi-metallic element (As)
• Well known poison and carcinogen
• Found in inorganic (toxic) and organic (nontoxic)
  forms
• Tasteless and odorless when mixed in water can
  be detected by chemical test
• Used in mining operations (for smelting), in
  outdated herbicide and pesticide and can leach
  into groundwater contaminating water supply

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The King of Poisons

• Discovered by Albertus Magnus around 1250 A.D.
• Ideal properties easily mixed in food or drink
• Since 1st century has been used as a homicidal
  agent
• Rumored that Napoleon was poisoned with arsenic

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Symptoms of Toxicity

• Symptoms of acute exposure
• Pulmonary edema
• Gastrointestinal effects including severe
  cramping, vomiting, and diarrhea
• Neurological seizures, cerebral edema, necrosis,
  and coma
• Also affects cardiovascular and renal system
• Can be fatal
• Symptoms of chronic exposure various cancers,
  peripheral neuropathy, muscle weakness,
  hyperkeratosis and hyperpigmentation of the skin,
  as well as paresthesia in hands and feet

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Pharmacokinetics

• Absorption
• 85 of inorganic As absorbed through intestine,
  also lung and skin
• When ingested as water-soluble salt it is rapidly
  absorbed with nearly 100 bioavailibility
• Distribution
• Rapid distribution form blood produces a serum
  half-life of 1 hour
• Metabolism
• Arsenate (5)? Arsenite (3)? Methylarsenite?
  Dimethylarsenite
• Excretion
• 46 to 68.9 of inorganic arsenic being excreted
  within the first 5 days of exposure

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Now..Are we ready for more 1 Carbons and
Methionine and SAM???
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Arsenic related to DNA Methylation

• Through series of reduction and oxidation
  reaction, inorganic As is methylated to
  monomethylarsonic acid (MMA) and dimethylarsinic
  acid (DMA)
• SAM (from methionine cycle) acts as methyl donor
• Insufficient folate and vitamin B12 may influence
  arsenic toxicity
• Result in aberrant gene expression because DNA
  methylation is altered
• Individuals with certain polymorphisms may be
  more susceptible to arsenicosis

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Acute Arsenic Toxicity

• Organic arsenic is found in trace amounts in
  living matter and is nontoxic
• Inorganic compounds are highly toxic and exist in
  two oxidation states either trivalent (arsenite,
  As3) or pentavalent (arsenate, As5)
• Arsenate (As5) is less toxic than arsenite
  (As3) but may undergo biotransformation to
  arsenite (As3)

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Arsenite (As3) Toxicity
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Krebs Cycle
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Arsenate (As5) Toxicity
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Managing Acute Arsenic Poisoning

• FLUID REPLACEMENT Enormous fluid deficits due
  to GI loss, capillary leakage, systemic
  inflammatory response ? IV fluids should be given
  at 2x normal rate
• CHELATING AGENTS Scavenge arsenic and bind it
  into a stable metal-chelate complex which can be
  excreted
• British Anti-Lewisite (Dimercaprol)
• Binds 30 mg for every 50 mg of BAL can cross
  blood-brain barrier
• Side effects fever, hypertension, can exacerbate
  fluid loss
• IM injection unpredictable bioavailability in
  patients with severe shock
• Contraindicated in patients with G6PD deficiency
  or peanut allergy
• Succimer (DMSA)
• Water-soluble analog of BAL, can be administered
  orally
• Chelates metal in a 11 ratio
• DMPS (Unithiol)
• Water-soluble BAL analog , can be administered
  orally, IV, or IM
• Binds metabolized (methylated) As3 species which
  often have increased toxicity
• Enhances excretion even after several days of BAL
  treatment

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References

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• Buschmann J, Berg M, Stengel C et al.
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  Mekong delta floodplains. Environment
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• Kile M and Ronnenberg A. Can folate intake reduce
  arsenic toxicity? Nutrition Reviews 2008
  66(6)349353
• Lai M, Boyer E, Kleinman M et al. Acute Arsenic
  Poisoning in Two Siblings. Pediatrics 2005 116
  (1)249-257
• Levin-Scherz JK, Patrick JD, Weber FH, Garabedian
  C Jr. Acute arsenic ingestion. Ann Emerg Med.
  1987 16 702 704
• Mishra D, Mehta A, and Flora S. Reversal of
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  Administration of DMSA and Its Analogues in
  Guinea Pigs Role of Glutathione and Linked
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• Sambu S and Wilson R. Arsenic in food and water
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• Smith R. Arsenic A Murderous History. Dartmouth
  Toxic Metals Research Program. http//www.dartmout
  h.edu/toxmetal/TXSHas.shtml