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2S PC & TC > U5.2 : HEAVY METALS AND CHELATORS > Flashcards

U5.2 : HEAVY METALS AND CHELATORS Flashcards

U

1
Q

Heavy Metal

Storage batteries, ammunition, metal alloys, solder, glass, plastics, pigments (in paints), Ceramics

A

Lead

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2
Q

Heavy Metal

No useful purpose in the human body

A

Lead

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3
Q

Heavy Metal (Pharmacokinetics)

absorbed slowly but consistently via respiratory and gastrointestinal tract

A

Lead

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4
Q

Heavy Metal

Lead affects _____ due to industrial exposure

A

Respiratory tract

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5
Q

Heavy Metal

Lead affects _____ due to non-industrial exposure

A

Intestinal tract

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6
Q

Heavy Metal

Up to 50% absorbed in children; Up to 10-15% absorbed in adults

A

Lead

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7
Q

Heavy Metal

may cause low dietary calcium, iron deficiency and ingestion on an empty stomach increases absorption

A

Lead

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8
Q

Heavy Metal

Distributed to the bone marrow, brain, kidney,
liver, muscle and gonads; then bones

A

Lead

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9
Q

Heavy Metal

Half-life of Lead

A

1-2 months

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10
Q

Heavy Metal

In Lead, 70% excreted in the _____

A

Urine

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11
Q

Heavy Metal

Multiple mechanism of actions of ______ include inhibition of enzyme functions, interference with action of essential cations, and oxidative stress generation

A

Lead

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12
Q

Heavy Metal

Multiple mechanism of actions of _______ gene expression changes, cell signaling alteration, and disruption of membrane integrity

A

lead

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13
Q

Heavy Metal

Major forms of Lead Intoxication

A
  • Inorganic Lead Poisoning
  • Organic Lead Poisoning
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14
Q

Heavy Metal (Lead)

Inorganic Major Routes

A

GI, Respiratory

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15
Q

Heavy Metal (Lead)

Organic Major Routes

A

Skin, GI, Respiratory

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16
Q

Heavy Metal (Lead)

Inorganic Distribution

A

Soft Tissues; redistributed to skeleton

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17
Q

Heavy Metal (Lead)

Organic Distribution

A

Soft Tissues (esp liver and CNS)

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18
Q

Heavy Metal (Lead)

Major Clinical Findings
CNS deficits; peripheral neuropathy; anemia; nephropathy; hypertension; reproductive toxicity

A

Inorganic

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19
Q

Heavy Metal (Lead)

Major Clinical Findings
- Encephalopathy

A

Organic

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20
Q

Heavy Metal (Lead)

Mechanism of Action

  • Inhibits enzymes
  • interferes with essential cations
  • alters membrane structure
A

Inorganic

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21
Q

Heavy Metal (Lead)

Mechanism of Action
Hepatic dealkylation (fast) -> Trialkyl metabolites (slow) -> dissociation to lead

A

Organic

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22
Q

Heavy Metal (Lead)

Metabolism and Elimination
- Renal (major)
- feces and breast milk (minor)

A

Inorganic

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23
Q

Heavy Metal (Lead)

Metabolism and Elimination
- Urine and feces (major)
- Sweat (minor)

A

Organic

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24
Q

Heavy Metal

Treatment includes immediate termination of exposure, supportive
care and chelation therapy

A

Lead

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25
Q

Heavy Metal

Treatment
Chelate it using Intravenous
edetate calcium disodium (CaNa2EDTA) at a dosage of 30-50 mg/kg/d by continuous infusion for up to 5 days only

A

Lead

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26
Q

Heavy Metal

Semiconductors in our devices , wood, preservatives, nonferrous alloys, glass, turf herbicide monosodium methane arsonate (MSMA)

A

Arsenic

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27
Q

Heavy Metal

  • Well-absorbed via respiratory and GI tract
  • Percutaneous absorption is limited
A

Arsenic

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28
Q

Heavy Metal

T/F Arsenic is metabolized in the liver and excreted in the urine (major), sweat and feces

A

T

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29
Q

Heavy Metal

Multiple mechanism of actions
- Inhibition of enzyme functions
- Oxidative stress generation
- Gene expression changes
- Cell signaling alteration

A

Arsenic

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30
Q

Heavy Metal

Major Route of Arsenic Intoxication

A

GI, Respiratory

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31
Q

Heavy Metal

Distribution of Arsenic Intoxication

A

Predominantly soft tissues (highest in liver and kidney). Tightly bound to skin, hair and nails

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32
Q

Heavy Metal

Major Clinical Findings
- Cardiovascular: shock, arrythmias
- CNS: Encephalopathy, Peripheral Neuropathy
- Others: Gastroenteritis, Pancytopenias, Cancer

A

Arsenic

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33
Q

Heavy Metal

Mechanism of Action Arsenic

A

Multiple

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34
Q

Heavy Metal

Metabolism and Elimination
- Methylation
- Excreted via Urine (major)
- Sweat and Feces (minor)

A

Arsenic

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35
Q

Heavy Metal

  • “Raindrop pattern”
  • Hyperpigmentation and hyperkeratosis involving hands and
    feet
A

Arsenic

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36
Q

Heavy Metal

Treatment
- Immediate termination of exposure, supportive
care and chelation therapy

A

Arsenic

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37
Q

Heavy Metal

Treatment
Acute Poisoning: Chelation with Unithiol 3-5
mg/kg every 4-6 hours or Dimercaprol every 4-6 hour

A

Arsenic

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38
Q

Heavy Metal

Quicksilver or liquid metal

A

Mercury

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39
Q

Heavy Metal

Electrolytic production of chlorine and caustic soda;
electrical equipment, thermometer, instruments, fluorescent lamps; dental amalgams; artisanal gold production

A

Mercury

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40
Q

Heavy Metal

an organomercurial preservative that are now removed from almost all vaccines

A

Thimerosal

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41
Q

Heavy Metal

T/F Environmental release of mercury from burning of fossil fuels contributes to bioaccumulation in fishes

A

T

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42
Q

Heavy Metal

Absorption varies depending on chemical form

A

Mercury

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43
Q

Heavy Metal

Absorbed from the lungs, GI tract, and percutaneous
route

A

Mercury

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44
Q

Heavy Metal

Distributed well into tissues (most concentrated in
kidneys)

A

Mercury

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45
Q

Heavy Metal

Mercury is excreted via

A

urine and feces

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46
Q

Heavy Metal : Type of Mercury

Major Route : Respiratory Tract

A

Elemental Mercury

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47
Q

Heavy Metal : Type of Mercury

Major Route : GI, skin (minor)

A

Inorganic Mercury

48
Q

Heavy Metal : Type of Mercury

Major Route :
GI, skin, respiratory tract (minor)

A

Organic Mercury

49
Q

Heavy Metal : Type of Mercury

Distribution :
Soft tissues esp. Kidneys and CNS

A

Elemental Mercury

50
Q

Heavy Metal : Type of Mercury

Distribution : Soft tissues esp. kidneys

A

Inorganic Mercury

51
Q

Heavy Metal : Type of Mercury

Distribution : Soft tissues

A

Organic Mercury

52
Q

Heavy Metal : Type of Mercury

Major Clinical Findings
- CNS: tremor, behavioral (erethism) gingivast matitis, periphera neuropathy; acrodynia pneumonitis

A

Elemental Mercury

53
Q

Heavy Metal : Type of Mercury

Major Clinical Findings
- Acute Renal Tubular Necrosis
- gastroenterit is
- CNS eects (rare)

A

Inorganic Mercury

54
Q

Heavy Metal : Type of Mercury

Major Clinical Findings
- CNS eects
- birth defects

A

Organic Mercury

55
Q

Heavy Metal : Type of Mercury

Mechanism of Action : Inhibits enzymes; alters membranes

A

Elemental Mercury, Inorganic Mercury

56
Q

Heavy Metal : Type of Mercury

Mechanism of Action : Inhibits enzymes; alter microtubules, neuronal structures

A

Organic Mercury

57
Q

Heavy Metal : Type of Mercury

Metabolism and Elimination of Elemental Mercury

A

Urine (major), feces (minor)

58
Q

Heavy Metal : Type of Mercury

Metabolism and Elimination of Inorganic Mercury

59
Q

Heavy Metal : Type of Mercury

Metabolism and Elimination of Organic Mercury

A

Deacylation. Fecal (alkyl, major); urine (after diacylation, minor)

60
Q

Heavy Metal

Treatment
Immediate removal from source, supportive
care and chelation therapy

61
Q

Heavy Metal

Treatment
Acute: Unithiol, dimercaprol or succimer

62
Q

Drugs used to prevent or reverse the toxic effects of
heavy metals on an enzyme or other cellular target, or
to accelerate the elimination of metal from the body

A

Chelators or Chelating Agents

63
Q

T/F The metal-mobilizing effects of a therapeutic chelating
agent may also redistribute some of the metal to vital
organs

64
Q

may also enhance excretion of essential cations

A

Zinc or Copper

65
Q

T/F The longer the half-life of a metal in a particular organ,
the less effectively they can be removed by chelation.

66
Q

T/F Chelators are only effective in free form or ionized form

67
Q

Chelators or Chelating Agents

  • Antidote to a warfare agent: Lewisite
  • As single-agent: acute poisoning
  • As conjunction with EDTA
A

Dimercaprol (2,3-Dimercaptopropanolol, BAL)

68
Q

Chelators or Chelating Agents

It prevents and reverses metal-induced inhibition of
sulfhydryl-containing enzyme

A

Dimercaprol (2,3-Dimercaptopropanolol, BAL)

69
Q

Chelators or Chelating Agents

  • Increases rate of excretion of arsenic and lead
  • Given via IM, excreted via kidneys
A

Dimercaprol (2,3-Dimercaptopropanolol, BAL)

70
Q

Chelators or Chelating Agents

Redistributes arsenic and mercury to CNS

A

Dimercaprol (2,3-Dimercaptopropanolol, BAL)

71
Q

Chelators or Chelating Agents

Water-soluble analog of dimercaprol

A

Succimer (Dimercaptosuccinic Acid, DMSA)

72
Q

Chelators or Chelating Agents

Treatment of children with blood lead concentration of
>45mcg/dL

A

Succimer (Dimercaptosuccinic Acid, DMSA)

73
Q

Chelators or Chelating Agents

  • prevents and reverses metal-induced inhibition of
    sulfhydryl-containing enzyme
  • increase rate of excretion of lead
  • decreases mercury content in kidney
A

Succimer (Dimercaptosuccinic Acid, DMSA)

74
Q

Chelators or Chelating Agents

Given oral, IV

A

Succimer (Dimercaptosuccinic Acid, DMSA)

75
Q

Chelators or Chelating Agents

  • Adverse effects: GI disturbances are the most common
  • Associated with increase in ALT, AST, mild neutropenia
A

Succimer (Dimercaptosuccinic Acid, DMSA)

76
Q

Chelators or Chelating Agents

Calcium disodium salt form of EDTA

A

Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)

77
Q

Chelators or Chelating Agents

Indicated mainly chelation of lead

A

Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)

78
Q

Chelators or Chelating Agents

  • Chelator of zinc, manganese and certain heavy
    radionuclide poisoning
  • Chelates extracellular metals ions much more effectively
    compared to intracellular metal ions
A

Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)

79
Q

Chelators or Chelating Agents

Limited oral absorption

A

Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)

80
Q

Chelators or Chelating Agents

Given IV infusion; Excreted via the kidney

A

Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)

81
Q

Chelators or Chelating Agents

Because on its effect on the calcium, the toxicity of the
EDTA would be ______

A

Hypocalcemia

82
Q

Chelators or Chelating Agents

Water-soluble analog of dimercaprol

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

83
Q

Chelators or Chelating Agents

No FDA-approved indication

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

84
Q

Chelators or Chelating Agents

Protective effects against mercury and arsenic

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

85
Q

Chelators or Chelating Agents

Increase urinary excretion mercury, arsenic and lead

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

86
Q

Chelators or Chelating Agents

Given Orally and IV (slow infusion)

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

87
Q

Chelators or Chelating Agents

Excreted via kidneys

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

88
Q

Chelators or Chelating Agents

Adverse effects: Dermatologic reactions are the most
common (urticaria, exanthems; isolated cases of SJS, erythema multiforme)

A

Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)

89
Q

Chelators or Chelating Agents

White, crystalline, derivative of Penicillin

A

Penicillamine (D-Dimethyl Cysteine)

90
Q

T/F D-Penicill amine is less toxic than the L–isomer form

91
Q

Chelators or Chelating Agents

  • Used primarily to treat or prevent Copper poisoning (i.e.
    Wilson’s Disease)
  • Also used in Severe Rheumatoid Arthritis
A

Penicillamine (D-Dimethyl Cysteine)

92
Q

Chelators or Chelating Agents

Adverse effects: Hypersensitivity, nephrotoxicity with
proteinuria, pancytopenia, pyridoxine insufficiency/Vit. B6 deficiency

A

Penicillamine (D-Dimethyl Cysteine)

93
Q

Chelators or Chelating Agents

Isolated from Streptomyces pilosus

A

Deferoxamine

94
Q

Chelators or Chelating Agents

The parenteral chelator of choice for iron poisoning

A

Deferoxamine

95
Q

Chelators or Chelating Agents

T/F Deferoxamine plus hemodialysis is useful in treatment of aluminum toxicity

96
Q

Chelators or Chelating Agents

Given IM or IV

A

Deferoxamine

97
Q

Chelators or Chelating Agents

Deferoxamine excreted in

98
Q

Chelators or Chelating Agents

Adverse Effects: Hypotension, flushing, abdominal discomfort, rashes, pulmonary complications

A

Deferoxamine

99
Q

Iron Chelating Agents

Isolated from Streptomyces pilosus

A

Deferoxamine

100
Q

Iron Chelating Agents

  • Parenteral chelator of choice for iron poisoning
  • Combined with hemodialysis for aluminum poisoning
A

Deferoxamine

101
Q

Iron Chelating Agents

Absorption, Metabolism and Elimination : Given IM or IV; Excreted via Urine

A

Deferoxamine

102
Q

Iron Chelating Agents

Adverse Effects: Hypotension, flushing, abdominal discomfort, rashes, pulmonary complications

A

Deferoxamine

103
Q

Iron Chelating Agents

Tridentate iron chelator

A

Deferasirox

104
Q

Iron Chelating Agents

  • Oral treatment of iron overload due to blood transfusion (esp. Seen in patients with thalassemia major and myelodysplastic syndrome
  • Relatively, more efficient in decreasing hepatic iron
A

Deferasirox

105
Q

Iron Chelating Agents

Absorption, Metabolism and Elimination : Given orally; Excreted in Bile

A

Deferasirox

106
Q

Iron Chelating Agents

Adverse Effect : Mild to moderate GI disturbances and skin rashes; Liver profile abnormalities

A

Deferasirox

107
Q

Iron Chelating Agents

Bidentate iron chelator

A

Deferiprone

108
Q

Iron Chelating Agents

  • Second-line oral chelator for iron overload due to blood transfusion in thalassemia major
  • Relatively, more efficient in decreasing cardiac iron
A

Deferiprone

109
Q

Iron Chelating Agents

Adverse Effects : Neutropenia, agranulocytosis

A

Deferiprone

110
Q

Iron Chelating Agents

Indicated for treatment of contamination with radioactive Cesium and intoxication with thallium salts

A

Prussian Blue (Ferric Hexacyanoferrate)

111
Q

Iron Chelating Agents

Ion exchange and mechanical trapping or adsorption

A

Prussian Blue (Ferric Hexacyanoferrate)

112
Q

Iron Chelating Agents

Given orally, minimal GI absorption (<1%), excreted via feces

A

Prussian Blue (Ferric Hexacyanoferrate)

113
Q

Iron Chelating Agents

Adverse effects: Constipation

A

Prussian Blue (Ferric Hexacyanoferrate)

114
Q

Iron Chelating Agents

Most utilized among the three

A

Deferoxamine

115
Q

Pharmacology of Chelators

A

Metallic Ion + Chelating agent = Metallic chelate

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