U5.2 : HEAVY METALS AND CHELATORS Flashcards
U (115 cards)
1
Q
Heavy Metal
Storage batteries, ammunition, metal alloys, solder, glass, plastics, pigments (in paints), Ceramics
A
Lead
2
Q
Heavy Metal
No useful purpose in the human body
A
Lead
3
Q
Heavy Metal (Pharmacokinetics)
absorbed slowly but consistently via respiratory and gastrointestinal tract
A
Lead
4
Q
Heavy Metal
Lead affects _____ due to industrial exposure
A
Respiratory tract
5
Q
Heavy Metal
Lead affects _____ due to non-industrial exposure
A
Intestinal tract
6
Q
Heavy Metal
Up to 50% absorbed in children; Up to 10-15% absorbed in adults
A
Lead
7
Q
Heavy Metal
may cause low dietary calcium, iron deficiency and ingestion on an empty stomach increases absorption
A
Lead
8
Q
Heavy Metal
Distributed to the bone marrow, brain, kidney,
liver, muscle and gonads; then bones
A
Lead
9
Q
Heavy Metal
Half-life of Lead
A
1-2 months
10
Q
Heavy Metal
In Lead, 70% excreted in the _____
A
Urine
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
12
Q
Heavy Metal
Multiple mechanism of actions of _______ gene expression changes, cell signaling alteration, and disruption of membrane integrity
A
lead
13
Q
Heavy Metal
Major forms of Lead Intoxication
A
- Inorganic Lead Poisoning
- Organic Lead Poisoning
14
Q
Heavy Metal (Lead)
Inorganic Major Routes
A
GI, Respiratory
15
Q
Heavy Metal (Lead)
Organic Major Routes
A
Skin, GI, Respiratory
16
Q
Heavy Metal (Lead)
Inorganic Distribution
A
Soft Tissues; redistributed to skeleton
17
Q
Heavy Metal (Lead)
Organic Distribution
A
Soft Tissues (esp liver and CNS)
18
Q
Heavy Metal (Lead)
Major Clinical Findings
CNS deficits; peripheral neuropathy; anemia; nephropathy; hypertension; reproductive toxicity
A
Inorganic
19
Q
Heavy Metal (Lead)
Major Clinical Findings
- Encephalopathy
A
Organic
20
Q
Heavy Metal (Lead)
Mechanism of Action
- Inhibits enzymes
- interferes with essential cations
- alters membrane structure
A
Inorganic
21
Q
Heavy Metal (Lead)
Mechanism of Action
Hepatic dealkylation (fast) -> Trialkyl metabolites (slow) -> dissociation to lead
A
Organic
22
Q
Heavy Metal (Lead)
Metabolism and Elimination
- Renal (major)
- feces and breast milk (minor)
A
Inorganic
23
Q
Heavy Metal (Lead)
Metabolism and Elimination
- Urine and feces (major)
- Sweat (minor)
A
Organic
24
Q
Heavy Metal
Treatment includes immediate termination of exposure, supportive
care and chelation therapy
A
Lead
25
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
Lead
26
Heavy Metal
Semiconductors in our devices , wood, preservatives, nonferrous alloys, glass, turf herbicide monosodium methane arsonate (MSMA)
Arsenic
27
Heavy Metal
- Well-absorbed via respiratory and GI tract
- Percutaneous absorption is limited
Arsenic
28
Heavy Metal
T/F Arsenic is metabolized in the liver and excreted in the urine (major), sweat and feces
T
29
Heavy Metal
Multiple mechanism of actions
- Inhibition of enzyme functions
- Oxidative stress generation
- Gene expression changes
- Cell signaling alteration
Arsenic
30
Heavy Metal
Major Route of Arsenic Intoxication
GI, Respiratory
31
Heavy Metal
Distribution of Arsenic Intoxication
Predominantly soft tissues (highest in liver and kidney). Tightly bound to skin, hair and nails
32
Heavy Metal
Major Clinical Findings
- Cardiovascular: shock, arrythmias
- CNS: Encephalopathy, Peripheral Neuropathy
- Others: Gastroenteritis, Pancytopenias, Cancer
Arsenic
33
Heavy Metal
Mechanism of Action Arsenic
Multiple
34
Heavy Metal
Metabolism and Elimination
- Methylation
- Excreted via Urine (major)
- Sweat and Feces (minor)
Arsenic
35
Heavy Metal
- “Raindrop pattern”
- Hyperpigmentation and hyperkeratosis involving hands and
feet
Arsenic
36
Heavy Metal
Treatment
- Immediate termination of exposure, supportive
care and chelation therapy
Arsenic
37
Heavy Metal
Treatment
Acute Poisoning: Chelation with Unithiol 3-5
mg/kg every 4-6 hours or Dimercaprol every 4-6 hour
Arsenic
38
Heavy Metal
Quicksilver or liquid metal
Mercury
39
Heavy Metal
Electrolytic production of chlorine and caustic soda;
electrical equipment, thermometer, instruments, fluorescent lamps; dental amalgams; artisanal gold production
Mercury
40
Heavy Metal
an organomercurial preservative that are now removed from almost all vaccines
Thimerosal
41
Heavy Metal
T/F Environmental release of mercury from burning of fossil fuels contributes to bioaccumulation in fishes
T
42
Heavy Metal
Absorption varies depending on chemical form
Mercury
43
Heavy Metal
Absorbed from the lungs, GI tract, and percutaneous
route
Mercury
44
Heavy Metal
Distributed well into tissues (most concentrated in
kidneys)
Mercury
45
Heavy Metal
Mercury is excreted via
urine and feces
46
Heavy Metal : Type of Mercury
Major Route : Respiratory Tract
Elemental Mercury
47
Heavy Metal : Type of Mercury
Major Route : GI, skin (minor)
Inorganic Mercury
48
Heavy Metal : Type of Mercury
Major Route :
GI, skin, respiratory tract (minor)
Organic Mercury
49
Heavy Metal : Type of Mercury
Distribution :
Soft tissues esp. Kidneys and CNS
Elemental Mercury
50
Heavy Metal : Type of Mercury
Distribution : Soft tissues esp. kidneys
Inorganic Mercury
51
Heavy Metal : Type of Mercury
Distribution : Soft tissues
Organic Mercury
52
Heavy Metal : Type of Mercury
Major Clinical Findings
- CNS: tremor, behavioral (erethism) gingivast matitis, periphera neuropathy; acrodynia pneumonitis
Elemental Mercury
53
Heavy Metal : Type of Mercury
Major Clinical Findings
- Acute Renal Tubular Necrosis
- gastroenterit is
- CNS eects (rare)
Inorganic Mercury
54
Heavy Metal : Type of Mercury
Major Clinical Findings
- CNS eects
- birth defects
Organic Mercury
55
Heavy Metal : Type of Mercury
Mechanism of Action : Inhibits enzymes; alters membranes
Elemental Mercury, Inorganic Mercury
56
Heavy Metal : Type of Mercury
Mechanism of Action : Inhibits enzymes; alter microtubules, neuronal structures
Organic Mercury
57
Heavy Metal : Type of Mercury
Metabolism and Elimination of Elemental Mercury
Urine (major), feces (minor)
58
Heavy Metal : Type of Mercury
Metabolism and Elimination of Inorganic Mercury
Urine
59
Heavy Metal : Type of Mercury
Metabolism and Elimination of Organic Mercury
Deacylation. Fecal (alkyl, major); urine (after diacylation, minor)
60
Heavy Metal
Treatment
Immediate removal from source, supportive
care and chelation therapy
Mercury
61
Heavy Metal
Treatment
Acute: Unithiol, dimercaprol or succimer
Mercury
62
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
Chelators or Chelating Agents
63
T/F The metal-mobilizing effects of a therapeutic chelating
agent may also redistribute some of the metal to vital
organs
T
64
may also enhance excretion of essential cations
Zinc or Copper
65
T/F The longer the half-life of a metal in a particular organ,
the less effectively they can be removed by chelation.
T
66
T/F Chelators are only effective in free form or ionized form
T
67
Chelators or Chelating Agents
- Antidote to a warfare agent: Lewisite
- As single-agent: acute poisoning
- As conjunction with EDTA
Dimercaprol (2,3-Dimercaptopropanolol, BAL)
68
Chelators or Chelating Agents
It prevents and reverses metal-induced inhibition of
sulfhydryl-containing enzyme
Dimercaprol (2,3-Dimercaptopropanolol, BAL)
69
Chelators or Chelating Agents
- Increases rate of excretion of arsenic and lead
- Given via IM, excreted via kidneys
Dimercaprol (2,3-Dimercaptopropanolol, BAL)
70
Chelators or Chelating Agents
Redistributes arsenic and mercury to CNS
Dimercaprol (2,3-Dimercaptopropanolol, BAL)
71
Chelators or Chelating Agents
Water-soluble analog of dimercaprol
Succimer (Dimercaptosuccinic Acid, DMSA)
72
Chelators or Chelating Agents
Treatment of children with blood lead concentration of
>45mcg/dL
Succimer (Dimercaptosuccinic Acid, DMSA)
73
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
Succimer (Dimercaptosuccinic Acid, DMSA)
74
Chelators or Chelating Agents
Given oral, IV
Succimer (Dimercaptosuccinic Acid, DMSA)
75
Chelators or Chelating Agents
- Adverse effects: GI disturbances are the most common
- Associated with increase in ALT, AST, mild neutropenia
Succimer (Dimercaptosuccinic Acid, DMSA)
76
Chelators or Chelating Agents
Calcium disodium salt form of EDTA
Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)
77
Chelators or Chelating Agents
Indicated mainly chelation of lead
Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)
78
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
Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)
79
Chelators or Chelating Agents
Limited oral absorption
Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)
80
Chelators or Chelating Agents
Given IV infusion; Excreted via the kidney
Edetate Calcium Disodium (Ethylenediaminetetraacetic Acid, EDTA)
81
Chelators or Chelating Agents
Because on its effect on the calcium, the toxicity of the
EDTA would be ______
Hypocalcemia
82
Chelators or Chelating Agents
Water-soluble analog of dimercaprol
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
83
Chelators or Chelating Agents
No FDA-approved indication
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
84
Chelators or Chelating Agents
Protective effects against mercury and arsenic
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
85
Chelators or Chelating Agents
Increase urinary excretion mercury, arsenic and lead
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
86
Chelators or Chelating Agents
Given Orally and IV (slow infusion)
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
87
Chelators or Chelating Agents
Excreted via kidneys
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
88
Chelators or Chelating Agents
Adverse effects: Dermatologic reactions are the most
common (urticaria, exanthems; isolated cases of SJS, erythema multiforme)
Unithiol (Dimercaptopropane Sulfonic Acid, DMPS)
89
Chelators or Chelating Agents
White, crystalline, derivative of Penicillin
Penicillamine (D-Dimethyl Cysteine)
90
T/F D-Penicill amine is less toxic than the L–isomer form
T
91
Chelators or Chelating Agents
- Used primarily to treat or prevent Copper poisoning (i.e.
Wilson’s Disease)
- Also used in Severe Rheumatoid Arthritis
Penicillamine (D-Dimethyl Cysteine)
92
Chelators or Chelating Agents
Adverse effects: Hypersensitivity, nephrotoxicity with
proteinuria, pancytopenia, pyridoxine insufficiency/Vit. B6 deficiency
Penicillamine (D-Dimethyl Cysteine)
93
Chelators or Chelating Agents
Isolated from Streptomyces pilosus
Deferoxamine
94
Chelators or Chelating Agents
The parenteral chelator of choice for iron poisoning
Deferoxamine
95
Chelators or Chelating Agents
T/F Deferoxamine plus hemodialysis is useful in treatment of aluminum toxicity
T
96
Chelators or Chelating Agents
Given IM or IV
Deferoxamine
97
Chelators or Chelating Agents
Deferoxamine excreted in
Urine
98
Chelators or Chelating Agents
Adverse Effects: Hypotension, flushing, abdominal discomfort, rashes, pulmonary complications
Deferoxamine
99
Iron Chelating Agents
Isolated from Streptomyces pilosus
Deferoxamine
100
Iron Chelating Agents
- Parenteral chelator of choice for iron poisoning
- Combined with hemodialysis for aluminum poisoning
Deferoxamine
101
Iron Chelating Agents
Absorption, Metabolism and Elimination : Given IM or IV; Excreted via Urine
Deferoxamine
102
Iron Chelating Agents
Adverse Effects: Hypotension, flushing, abdominal discomfort, rashes, pulmonary complications
Deferoxamine
103
Iron Chelating Agents
Tridentate iron chelator
Deferasirox
104
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
Deferasirox
105
Iron Chelating Agents
Absorption, Metabolism and Elimination : Given orally; Excreted in Bile
Deferasirox
106
Iron Chelating Agents
Adverse Effect : Mild to moderate GI disturbances and skin rashes; Liver profile abnormalities
Deferasirox
107
Iron Chelating Agents
Bidentate iron chelator
Deferiprone
108
Iron Chelating Agents
- Second-line oral chelator for iron overload due to blood transfusion in thalassemia major
- Relatively, more efficient in decreasing cardiac iron
Deferiprone
109
Iron Chelating Agents
Adverse Effects : Neutropenia, agranulocytosis
Deferiprone
110
Iron Chelating Agents
Indicated for treatment of contamination with radioactive Cesium and intoxication with thallium salts
Prussian Blue (Ferric Hexacyanoferrate)
111
Iron Chelating Agents
Ion exchange and mechanical trapping or adsorption
Prussian Blue (Ferric Hexacyanoferrate)
112
Iron Chelating Agents
Given orally, minimal GI absorption (<1%), excreted via feces
Prussian Blue (Ferric Hexacyanoferrate)
113
Iron Chelating Agents
Adverse effects: Constipation
Prussian Blue (Ferric Hexacyanoferrate)
114
Iron Chelating Agents
Most utilized among the three
Deferoxamine
115
Pharmacology of Chelators
Metallic Ion + Chelating agent = Metallic chelate
