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Disease and Ther. Final > Heavy metals Chelators > Flashcards

Heavy metals Chelators Flashcards

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1
Q

Toxicology

A

study of adverse effects of a chemical, physical, or biological agent

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2
Q

Toxicity

A

the ability of a material to damage a biological system, cause injury, or impair function

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3
Q

What effects degree of toxicity

A

dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals

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4
Q

Hazard

A

ability of an agent to cause toxicity

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5
Q

Risk

A

the expected frequency of exposure to a hazardous agent

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6
Q

Route of exposure

A

Route of entry into body

inhalation, transdermal, oral mucosal

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7
Q

Duration of Exposure

A

may effect selection of treatment

acute vs. chronic

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8
Q

ADME

A

the Adsorption, Distribution, Metabolism, and Excretion of toxic substances and their metabolites

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9
Q

Clearance

A

measure of plasma cleared per unit time

sum of both renal and hepatic contributions

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10
Q

1st order clearance

A

normal conditions

eliminations of drugs/chemicals is proportional to their plasma concentration

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11
Q

Zero order kinetics

A

when plasma levels become very high, protein binding and normal metabolism can both become saturated, rate of elimination can become fixed
More drug will be delivered into circulation in unbound fraction

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12
Q

Volume of distribution

A

apparent volume into which a substance is distributed

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13
Q

Which volume of distribution is more difficult to remove (like with hemodialysis)

A

Large volume of distribution is more difficult to remove than small volume of distribution

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14
Q

Bioaccumulation

Biomagnification

A
  • accumulation of a toxic agent when the uptake exceeds the organism’s ability to metabolize/excrete
  • Biomagnification: increases in the relative amount of contaminant in a biological system as it passes up the food chain
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15
Q

Why, at very high blood concentrations, do normal kinetic properties of drugs or toxins change

A

Larger, unbound free fractions

prolonged half life and increase toxicity

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16
Q

What defines metals as heavy

A

high atomic weight and having a density at least five times greater than that of water (specific density of more than 5g/cm3)

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17
Q

Top 3 most toxic substances

A
  1. Lead
  2. Mercury
  3. Arsenic
  4. Cadmium
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18
Q

How do heavy metals interfere with normal biological processes

A

by competing with normal substrates

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19
Q

Chelators and half life

A

the shorter the half life, the more effective it is to use chelators to remove heavy metals

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20
Q

Primary exposure sources of lead

A 
Building materials/construction
Batteries
Lead pipes
paint
soil, dust, water 
industry
fold remedies
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21
Q

Why is lead exposure particularly detrimental to young children

A

Their bodies absorb b/c Pb competes with Ca and growing bodies require more Ca.
children absorb more than 50% consumed
adults - about 10-15%
Kids suck on stuff

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22
Q

Half life of lead

A

1-2 months

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23
Q

Symptoms of lead poisoning

A

Headaches
neurocognitive deficits
kidney damage

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24
Q

Main repository in body for lead burden

A

Substitutes for Ca in bone

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25
What are Burtonian lines
Lead lines causing a darkening of the gingiva
26
Mechanism of leads toxicity
Interferes with Ca us Causes anemia Causes immunosuppression
27
treatment regimen for lead toxicity - recommended chelators
Remove exposure | Chelators - EDTA, removes Pb from bone slowly and requires multiple chelating treatments
28
Mercury primarily used in what form
methyl/Hg form
29
Primary exposure sources of mercury
Fish Amalgam (CDC says it's not a problem) Thermometers
30
Mechanism of mercury toxicity
Reacts with selenium (necessary for reducing oxidized vitamin C and E) Can cause gingivostomatitis
31
Symptoms of mercury poisoning
Mad hatter disease Neurological Psychiatric problems Gingivostomatitis
32
CDC's conclusions regarding mercury exposure in thimerosal in flu vaccines and dental amalgam
other than redness and swelling at injection site | neither have evidence of causing harm
33
Treatment regimen for mercury toxicity - including chelators
Chelators - Dimercaprol and Succimer
34
Why is dimercaprol contraindicated in chronic mercury intoxication
Chronic use of dimercaprol can cause serious renal toxicity
35
Exposure sources of Arsenic
Industry Groundwater Arsenite - used in chemotherapeutics for leukemia
36
Toxicokinetics of Arsenic - route of intake
absorbed through respiratory mucosa and GI tract | poor skin absorption
37
Symptoms/effects of arsenic
Fatigue, anemia, renal failure, hyperpigmentation Carcinogenic in lungs, skin, and bladder hemolytic on RBCs
38
Mechanism of arsenic toxicity
``` interferes with enzyme function increases ROS and oxidative stress interferes with signal transduction hemolytic effects on RBCs Carcinogenic ```
39
Treatment for acute arsenic intoxication
Decontamination and supportive care Chelators: Unithiol or Dimercaprol Emperic chelation if exposure is suspected
40
Treatment for chronic arsenic intoxication
Supportive care Dietary supplementation with folate No chelators since chronic arsenosis leads to irreversible damage to several vital organs, carcinogenic
41
Treatment for acute arsine gas intoxication
Blood exchange hemodialysis and transfusions aggressive hydration No chelators - no benefit
42
How do chelators work on heavy metals
They render heavy metal ions unavailable for covalent interactions
43
How does the half-life of the heavy metal effect the ability of a chelator to remove it from a target organ
The longer the half life, the less effective the chelator action
44
Is it better to treat with chelators quickly or to wait
Most effective if administered ASAP after exposure
45
Dimercaprol: Approved for which heavy metal poisonings as a monotherapy
Arsenic (acute) and Mercury | Combo with Edetate calcium disodium for severe lead poisoning
46
Dimercaprol monotherapy contraindicated for what
Chronic exposure to lead | b/c it redistributes larger doses of lead to CNS
47
Dimercaprol Combo with what for chronic poisoning of what
Combo with CaNa2-EDTA (edetate calcium disodium) for severe lead exposure
48
Is Dimercaprol water soluble
no (cannot give orally)
49
Only route of administration for dimercaprol
Intramuscular (i.m.)
50
Therapeutic index of dimercaprol compared to succimer or unithiol
It can be very toxic, especially on kidneys | Succimer has replaced dimercaprol for the most part
51
Succimer
Water-soluble form of dimercaprol | For oral use only
52
Succimer approved for which heavy metal poisonings
Lead Arsenic Mercury
53
Succimer's main mechanism for removing heavy metals
Binds to cysteine to form mixed disulfides which are excreted by the kidney
54
Half life of Succimer
2-4 hours
55
Adverse effects of Succimer
only diarrhea/GI upset, maybe mild rashes | much better than dimercaprol
56
Edetate Calcium Disodium (CaNa2-EDTA) approved for which heavy metal poisonings
Lead
57
Edetate Calcium disodium targets intra or extra-cellular lead
Extra cellular
58
Edetate calcium only route of administration
Intravenous
59
Half life of edetate calcium disodium | excretion
1 hour | excreted 100% by kidney
60
Edetate calcium disodium contraindicated for what population
Anuric patients | excreted by kidneys
61
Unithiol another form of what routes of administration
Another water-soluble form of dimercaprol | Orally or IV
62
Half life of Unithiol
20 hours
63
Unithiol effective against which heavy metals | FDA approved for which
Mercury Arsenic Lead FDA approved for none
64
Biocompatibility
ability of a material to elicit an appropriate biological response in a given application in the body
65
4 biocompatibility criteria for the ideal dental material
Should not be harmful to pulp or soft tissues Should not contain toxic diffusable substances that may be released and absorbed into the circulatory system to cause systemic toxicity Should be free of potentially sensitizing agents that may cause allergic reactions Should have NO carcinogenic potential
66
Most common allergic reactions observed in dental practices | How to avoid them
Allergic contact dermatitis: distal fingers and tips after repeated exposure to monomers of bond - wear gloves wash hands Latex Allergies - use non-latex Allergies to denture base materials - soak in water 24 hours before first-time use
67
What step releases mercury the most
Polishing amalgam
68
How to avoid pulpitis from unpolymerized monomers in resin composite deep fillings
Use twice the recommended time of exposure Cure in increments Zinc phosphate cement Glass ionomer
69
How to avoid lesions caused by zinc phosphate cement
Use proper mix or alternatively use a resin-modified glass ionomer cement Make sure it isn't too thin
70
How to reduce cytotoxicity of acrylate bonding agents
rinse with tap water between applications of subsequent reagents
71
Importance of ventilation in lab with metals
Beryllium dust Nickel dust Beryllium vapors
72
Mechanism of cyanide poisoning
not a heavy metal, but very common | prevents cells of body from getting oxygen and ATP, causing cell death
73
Antidote for Cyanide
hydroxycobalamin - reacts with cyanide to form cyanocobalamin which is excreted by kidneys

Disease and Ther. Final (7 decks)

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