MT6314 HEAVY METALS AND CHELATORS Flashcards
(148 cards)
1
Q
Heavy metals include?
A
- Lead
- Arsenic
- Mercury
2
Q
Chelators include?
A
- Dimercaprol
- Succimer
- Edetate Calcium Disodium
- Unithiol
- Penicillamine
- Deferoxamine
- Deferasirox and Deferiprone
- Prussian Blue
3
Q
Oldest occupational and environmental disease in the world
A
Lead poisoning
4
Q
Used in storage batteries, ammunition, metal alloys, solder, glass, plastics, pigments and ceramics
A
Lead
5
Q
Presence of lead where led to exposure in children and adults?
A
Folk medicine and cosmetics
6
Q
Low level of lead exposure may have subtle adverse clinical effects on what in children and adults?
A
Children - neurocognitive function
Adults - cardiovascular
7
Q
Does lead have a purpose in the body?
A
No
8
Q
Lead is absorbed slowly but consistently via?
A
respiratory and gastrointestinal tract
9
Q
Respiratory or GI exposure in lead: industrial exposure
A
Respiratory
10
Q
Respiratory or GI exposure in lead: nonindustrial
exposure
A
GI
11
Q
Up to how much lead is absorbed in children and adults?
A
- Up to 50% absorbed in children
- Up to 10-15% in adults
12
Q
What are the causes of worsening lead absorption?
A
Low dietary calcium, iron deficiency and ingestion on an empty stomach increases absorption
13
Q
T or F: Lead is absorbed well into the skin
A
F, poor absorption on skin
14
Q
Which heavy metal: Distributed predominantly in the soft tissues, avidly bound on skin, hair, and nails
A
Arsenic
15
Q
What form of lead: Causes encephalopathy and is distributed into the soft tissues especially liver, CNS
A
Tetraethyl lead (organic lead)
16
Q
Which heavy metal: Major route of absorption is the GI and respiratory tract
A
Arsenic and Lead
17
Q
Which heavy metal: MOA inhibits enzymes, interferes with oxidative phosphorylation, alters cell signaling, gene expression
A
Arsenic
18
Q
What form of lead: MOA inhibits enzymes, interferes with essential cations, alters membrane structure
A
Inorganic lead
19
Q
Which heavy metal: MOA inhibits enzymes, alters membranes
A
Mercury
20
Q
Which heavy metal: metabolism includes methylation, renal, and sweat and feces
A
Arsenic
21
Q
Which form of mercury: Found only in respiratory tract
A
Elemental mercury
22
Q
Which form of mercury: causes acute renal tubular necrosis and gastroenteritis
A
Inorganic mercury
23
Q
Which heavy metal: Mechanism includes deacylation
A
Organic alkyl, aryl
24
Q
99% bound to RBCs, 1% free in plasma
A
Lead
25
Where is lead distributed?
to bone marrow, brain, kidney, liver, muscle and gonads; then bones
26
Lead also crosses the?
Hint: potential harm to the fetus
Placenta
27
Half life of lead? How about in bones?
1-2 months
In bones: years to decades
28
How much lead is excreted in urine?
70%
29
The multi systemic toxic effects of lead are mediated by?
Inhibition of enzymatic function
Interference with action of essential cations (calcium, zinc, iron)
Oxidative stress generation
Gene expression changes
Cell signaling alteration
Disruption of membrane integrity
30
Whose CNS is the most sensitive taft organ for lead toxicity?
Fetus and young children
31
T or F: Adults are less sensitive to the CNS effects of lead
T
32
Occurs at blood lead concentrations of higher than 100 mcg/dL
Lead encephalopathy
33
Lead can cause normocyctic or hypo chromic _____.
anemia
34
May occur with high exposure to lead
Frank hemolysis
35
Effects off lead to the kidneys?
Renal interstitial fibrosis and nephrosclerosis
Lead neuropathy
Azotemia
36
Effects of lead on reproductive system?
Stillbirth or spontaneous abortion
37
Effects of lead on the GI?
Loss of appetite, constipation, diarrhea (less common)
Lead colic
Gingival lead lines
38
Effects of lead on cardiovascular system?
Elevated BP
39
Diagnosis of lead intoxication is best measured through?
Measuring lead in whole blood
40
Treatment for lead poisoning?
IV EDTA 30-50mg/kg/d by continuous infusion for up to 5 days only
Oral Succimer (DMSA) after 5 days
Retained lead objects require gastrointestinal
decontamination
41
Occurring element in the earth's crust used in commercial and industrial products
Arsenic
42
Seen in semiconductors, wood preservatives, nonferrous alloys, glass and turf herbicide monosodium methane arsonate (MSMA)
Arsenic
43
Type of arsenic produced by the semiconductor industry
Arsine (arsenous hydride)
44
T or F: Groundwater may contain high amounts of arsenic
T
45
T or F: Arsenic used to be involved in pharmaceutical use
T
46
Contains 1% potassium arsenide and used for medicine in the 18th century
Fowler's solution
47
Designed in the 20th century as warfare agents
Lewisite
48
T or F: Melarsoprol is a trivalent arsenical
T
49
Arsenic is well-absorbed via?
Respiratory and GI, percutaneous absorption is limited
50
Arsenic is metabolized by?
Liver via methylation
51
Arsenic excreted in?
Urine (major), sweat and feces
52
Inorganic arsenide or its metabolites may induce?
Oxidative stress, alter gene expression, and interfere with cell signal transduction
53
Multiple mechanism of actions of arsenic?
* Inhibition of enzyme functions
* Oxidative stress generation
* Gene expression changes
* Cell signaling alteration
54
Interferences with enzyme function in arsenic may lead to?
sulfhydryl groups binding by trivalent arsenic or by substitution for phosphate
55
Which is more toxic, trivalent form of methylated metabolites or inorganic parent compounds of arsenic?
Trivalent form of methylated metabolites
56
Major routes of arsenic intoxication?
GI, respiratory
57
Distribution of arsenic?
Predominantly soft tissues (highest in liver and
kidney). Tightly bound to skin, hair and nails
58
Major clinical findings of arsenic intoxication?
Cardiovascular: shock, arrythmias;
CNS: Encephalopathy, Peripheral Neuropathy;
Others: Gastroenteritis, Pancytopenias, Cancer
59
Metabolism and Elimination of arsenic?
Methylation; Excreted via Urine (major), Sweat and Feces (minor)
60
Chronic inorganic arsenic poisoning also causes?
“Raindrop pattern”: Hyperpigmentation and hyperkeratosis involving hands and feet
61
Treatment of arsenic intoxication?
*Immediate termination of exposure, supportive care and chelation therapy
*Gut decontamination if appropriate
*Acute Poisoning: Chelation with Unithiol 3-5mg/kg every 4-6 hours or Dimercaprol every 4-6 hours
62
T or F: Arsenic disappears quickly from the blood
T
63
What treatment has also been effective in animal models and has a higher therapeutic index than dimercaprol?
Succimer
64
Quicksilver or liquid metal, mined predominantly as HgS in cinnabar ores
Mercury
65
Found in electrolytic production of chlorine and caustic soda; electrical equipment, thermometer, fluorescent lamps, dental amalgams and artisanal gold production
Mercury
66
An organomercurial now removed from almost all vaccines
Thimerosal
67
Environmental release of mercury is from?
burning of fossil fuels contributed to bioaccumulation in fishes
68
Absorption of mercury varies depending on?
Chemical form
69
Mercury is absorbed in the?
lungs, GI tract, and percutaneous route
70
Mercury is distributed well into?
Tissues, most concentrated in kidneys
71
What form of mercury is quite volatile and can be absorbed in the lungs, but poorly absorbed in GI?
Elemental mercury
72
What kind of mercury is well-absorbed into the skin?
Alkylmercury compounds
73
Has a half-life of approximately 50 days, and undergoes biliary excretion and enterohepatic circulation
Methylmercury
74
Mercury is absorbed in the?
lungs, GI tract, and percutaneous route
75
What form of mercury: major route is respiratory
Elemental
76
What form of mercury: Major route is skin and GI
Inorganic
77
What form of mercury: GI, skin, repiratory and distributed in soft tissues only
Organic
78
Treatment of mercury intoxication?
Immediate removal from source, supportive care
and chelation therapy
Acute: Unithiol, dimercaprol or succimer
Dimecaprol should never be used for elemental or
organic mercury intoxication
79
Acute or chronic mercury intoxication: erethism
Chronic
80
Acute or chronic mercury intoxication: chemical pneunomitis and noncardiogenic pulmonary edema
Acute
81
Acute or chronic mercury intoxication: treatment is succorer, dimercaprol and unithiol
Acute
82
Acute or chronic mercury intoxication: treatment is unithiol and succimer
Chronic
83
Drugs used to prevent or reverse toxic effects of heavy metals on an enzyme or cellular target to accelerate the elimination of metal from the body
Chelators
84
The metal-mobilizing effects of a therapeutic chelating agent may also?
redistribute some of the metal to vital organs
85
Chelating agents contain one or more coordinating atoms such as?
oxygen, sulfur, or nitrogen that donates a pair of electrons to a catatonic metal ion to form one or more coordinate-covalent bonds
86
Chelating agents may also enhance excretion of?
essential cations (Zinc, Copper)
87
The longer the half-life of a metal in a particular organ, _____.
the less effectively they can be removed by chelation.
88
Benefits of chelation
Effective against acute poisoning
Form non-toxic complexes
Remove metal from soft tissue
Oral therapy is available
89
Drawbacks of chelation
Redistribution of toxic metal
Essential metal loss
No removal of metal from intracellular sites
Hepatotoxicity and nephrotoxicity
Poor clinical recovery
Pro-oxidant effects
Headache, nausea, increased BP
90
Dimercaprol redistributes what to the brain while enhancing the excretion of what?
Redistributes mercury and arsenic
Excretes urinary mercury and arsenic
91
When is the capacity of the chelating agents greatest?
When they are administered very soon after an acute metal exposure
92
Antidote to a warfare agent
Lewisite
93
Dimercaprol as a single agent treats?
acute poisoning by arsenic and inorganic mercury
94
Oily, colorless liquid with strong mercaptan-like odor
Dimercaprol
95
Other names for dimercaprol
2,3-Dimercaptopropanolol, BAL
96
What form of administration of dimercaprol appears to be readily absorbed, metabolized, and excreted by the kidney within 4-8hrs?
IM administered BAL
97
BAL prevents and reverses?
metal-induced inhibition of sulfhydryl-containing enzyme
98
Succimer other names?
Dimercaptosuccinic Acid, DMSA
99
Water-soluble analog of dimercaprol that prevents and reverses the metal-induces inhibition of sulfhydryl-containing enzyme to protect against lethal effects of arsenic
DMSA
100
Succimer is a treatment for?
children with blood lead concentration of >45mcg/dL
101
DMSA increases the rate of excretion of ___ and decreases excretion of _______
Lead
Mercury
102
DMSA has a protective agent against?
Arsenic
103
How if DMSA given?
Oral or IV
104
DMSA iso sed against the poisoning of?
Mercury and arsenic
105
T or F: Succimer has an impact on the calcium, iron and magnesium stores of the body
F, negligible
106
Succimer is been associated with increase in?
ALT, AST, mild neutropenia
107
Other name for Edetate Calcium Disodium?
Ethylenediaminetetraacetic Acid, EDTA
108
Where does EDTA come from?
Calcium disodium salt form of EDTA
109
EDTA is indicated mainly for?
chelation of lead, zinc, manganese and certain heavy radionucleotide poisoning
110
T or F: EDTA penetrates the cell membranes well
F, poorly
111
What character of EDTA limits oral absorption?
highly polar ionic character
112
How is EDTA usually administered?
IV infusion
113
Other name for Unithiol?
Dimercaptopropanesulfonic Acid, DMPS
114
Water-soluble analog of dimercaprol with no FDA-approved indications
Unithiol
115
How is unithiol administered?
Orally and IV (slow infusion)
116
Unithiol is a protective agent against?
mercury and arsenic
117
Unithiol increases urinary excretion of?
mercury, arsenic and lead
118
Elimination of the half life of unithiol takes about how long?
20hours
119
IV unithiol offers advantages over?
IM dimercaprol and oral succimer in initial treatment of severe acute mercury or arsenic poisoning
120
Unithiol can be a substitute to what in the treatment of lead intoxication?
Succimer
121
What syndrome has been reported to occur within treatment using unithiol?
Steven-Johnson syndrome
122
White, crystalline, derivative of Penicillin to treat or prevent Copper poisoning
Penicillamine (D-Dimethylcysteine)
123
used in Severe Rheumatoid Arthritis
Penicillamine (D-Dimethylcysteine)
124
How is Penicillamine (D-Dimethylcysteine) absorbed?
Oral
125
What is less toxic than the L-isomer form?
D-Penicillamine
126
What replaced penicillamine due to having stronger metal-mobilizing capacity and lower-adverse effect profile?
Succimer
127
Deferoxamine is isolated from?
Streptomyces pilosus
128
The parenteral chelator of choice for iron poisoning
Deferoxamine
129
Useful in treatment of aluminum toxicity
Deferoxamine plus hemodialysis
130
How is deferoxamine administered?
IM or IV
131
Deferoxamine is poorly absorbed in this route and may increase iron absorption
Oral
132
Rapid IV administration of Deferoxamine may result in?
hypotension
133
Tridentate iron chelator
Deferasirox
134
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
135
Adverse Effects include hypotension, flushing, abdominal discomfort, rashes, pulmonary complications
Deferoxamine
136
Given orally; Excreted in Bile
Deferasirox
137
Adverse effects include mild to moderate GI disturbances and skin rashes; Liver profile abnormalities
Deferasirox
138
Bidentate iron chelator
Deferiprone
139
Second-line oral chelator for iron overload due to blood transfusion in thalassemia major
Relatively, more efficient in decreasing cardiac iron
Deferiprone
140
Given orally; excreted via urine
Deferiprone
141
Adverse effects include Neutropenia, agranulocytosis
Deferiprone
142
Prussian Blue other name?
Ferric Hexacyanoferrate
143
Prussian blue is an indicated treatment for?
contamination with radioactive Cesium and intoxication with thallium salts
144
Ferric Hexacyanoferrate is a hydrated crystalline compound in which ____ are coordinated with _____
Fe2+ and Fe3+ with cyanide in a cubic lattice structure
145
Prussian Blue is used for?
Ion exchange and mechanical trapping or adsorption
146
How is Prussian Blue administered and excreted?
orally, minimal GI absorption (<1%), excreted via
feces
147
Why does Prussian Blue have minimal GI absorption?
Its complexes form with cesium or thallium which are non absorbable
148
Adverse effects of Prussian Blue?
Constipation
