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PMC 622 > Heavy Metals > Flashcards

Heavy Metals Flashcards

1
Q

Background

A
  1. Metals accumulate
  2. Not metabolized
  3. Bind to target proteins, enzymes via S, O, N
  4. Chelators used for detoxification
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2
Q

Properties of an Ideal Chelating Agent

A
  1. Chelator-heavy metal complex less toxic than metal
  2. Enhances excretion of metal
  3. Chelate metal at physiologic pH
  4. Not readily metabolized
  5. Hydrophilic
  6. Has greater affinity for metals than calcium or iron in body
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3
Q

Calcium Disodium EDTA

A
  1. Metal displaces calcium in center of molecule
  2. IV/IM administration
  3. Tx: Lead and cadmium
  4. Metal-EDTA complex excreted in urine: contraindicated in renal disease
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4
Q

Succimer

A
  1. DMSA
  2. Sulfhydryl groups bind to metal and excreted in urine
  3. Administered orally
  4. Lead toxicity
  5. Low compliance due to nausea and bad taste
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5
Q

Dimercaprol (BAL)

A
  1. SH groups bind to metal
  2. Tx: Lead, Arsenic, and inorganic mercury poisoning
  3. IM Administration (in peanut oil)
  4. Metal-BAL complex excreted in urine and bile: dissociates in acidic urine
  5. Contraindicated in liver disease
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6
Q

Penicillamine

A
  1. Sulfhydryl containing agent
  2. Complex excreted in urine: contraindicated in renal disease
  3. Oral administration
  4. DOC in Wilson’s disease
  5. Agranulocytosis is major adverse effect
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7
Q

Lead

A
  1. Exposed by ingestion (water, soil, paint chips, pottery made outside US) or inhalation
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8
Q

Absorption and Distribution of Lead

A
  1. Children absorb it >5 times higher than adults
  2. Distributes first to liver, kidney, RBC
  3. RBC have >95% of lead in blood bound to hemoglobin
  4. Redistributes to bone replacing calcium to form tertiary lead phosphate
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9
Q

Lead Poisoning

A
  1. Blood, microcytic anemia, basophilic stipling and hemolysis (acute)
  2. GI, lead colic (chronic)
  3. Nerve, muscle weakness, memory loss, lead palsy (chronic)
  4. Lead encephalopathy: most serious condition, convulsions, cerebral edema, death
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10
Q

Neurological Target Tissues for Lead

A
  1. Peripheral, axon degeneration
  2. Brain, lead interferes with calcium dependent reactions in brain
  3. Brain is most sensitive organ
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11
Q

Hematologic Target Tissues for Lead

A
  1. Most sensitive indicator of toxicity
  2. Lead inhibits heme synthesis
  3. Basophilic stipling due to ppt of RNA
  4. Anemia due to decreased life span and heme synthesis
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12
Q

Blood and Urinary Indicators of Lead

A
  1. Inhibits 2 Sulfhydryl dependent enzymes
  2. Cause increase urinary levels of delta-aminolevulinic acid
  3. Lead levels in whole blood sensitive indicator of toxicity
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13
Q

Chelation Therapy

A
  1. Low levels, asymptomatic (succimer PO, Penicillamine PO: not FDA approved)
  2. Aggressive Therapy (Calcium Disodium EDTA IV, Dimercaprol IM)
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14
Q

Mercury

A
  1. 3 forms: elemental, inorganic, and organomercurial
  2. Bind to Sulfhydryl groups, inactivate proteins and enzymes
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15
Q

Elemental Mercury

A
  1. Inhalation: respiratory and neurological damage
  2. Not toxic orally
  3. Unionized so crosses BBB
  4. In RBC, converted from 0 valence to +2
  5. Toxicity tremor, irritability, erethism,
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16
Q

Inorganic Mercury

A
  1. Oral exposure binds to SH-proteins in mouth and esophagus causing a gray color
  2. GI, vomiting, hematochezia
  3. Renal: PCT, chronic tubular and glomerular damage
  4. Photophobia and acrodynia
17
Q

Organomercurials

A
  1. Most toxic form
  2. Target is nervous system, readily enters the brain: muscle tremor, visual field constriction, ataxia
18
Q

Tx of Mercury Toxicity

A
  1. Elemental and Inorganic mercury use Penicillamine and Dimercaprol
  2. Methyl mercury: Penicillamine shows moderate success, Dimercaprol contraindicated because in increases brain levels
19
Q

Arsenic

A
  1. Forms: inorganic (As3+ and As5+), organoarsenical, and arsine gas
20
Q

Arsenic MOA

A
  1. As3+ — binds SH groups
  2. As5+ — replaces P in ATP production causing uncoupling of oxidative phosphorylation
  3. Ash3 hemolysis
21
Q

Arsenic Toxicity

A
  1. Vascular: VD, increases capillary permeability, arrhythmia
  2. GI: increased blood flow, loss of albumin into SI coagulates giving a gelatinous diarrhea called rice water diarrhea
  3. Skin: cancer and hyperkeratosis
  4. Arsine gas: hemolysis
  5. Kidney: PCT and glomerular
22
Q

Chronic Arsenic Toxicity

A
  1. Muscle weakness
  2. Hyperkeratosis
  3. Arrhythmia
  4. Enlarged liver
  5. Garlic odor to breath and sweat
  6. Mee’s line on fingernails
23
Q

Tx for Arsenic Toxicity

A
  1. Penicillamine
  2. Dimercaprol
  3. Arsine gas chelation therapy ineffective so Tx symptoms
24
Q

Cadmium

A
  1. Ingestion: target is kidney
  2. Inhalation: target kidney and lung, kidney: PCT necrosis, lung: pulmonary edema, irritation and chronic exposure causes emphysema
25
Q

Cadmium Toxicity and Metallothionein

A
  1. Metallothionein is an Inducible protein: induced by cadmium, mercury, and arsenic exposure
  2. Cadmium accumulates in liver and kidney bound to Metallothionein
26
Q

Tx for Cadmium Toxicity

A
  1. Chelation Therapy: Disodium EDTA, BAL contraindicated in renal toxicity
  2. Monitor urinary B2-microglobulin
27
Q

Wilson’s Disease

A
  1. Inappropriately high copper levels
  2. Defect in ATP7B protein: impacts biliary copper excretion, diminished copper incorporation with ceruloplasmin
  3. First line of therapy is Penicillamine
  4. Trientine alternate choice chelator when Penicillamine not tolerated

PMC 622 (3 decks)

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